Cardiology

Approximately half of adults with idiopathic pulmonary arterial hypertension (IPAH) had nonplexiform vasculopathy characterized in part by severe pulmonary microvascular remodeling, based on data from 50 individuals.

The clinical phenotype of IPAH was historically described as a rapidly progressive rare disease in young women and characterized by plexiform lesions, wrote Esther J. Nossent, MD, of Amsterdam University Medical Centers, Amsterdam, the Netherlands, and colleagues. However, the patient population with IPAH has become older and predominantly men, and the nature of vascular phenotypes and histologic patterns in patients with contemporary IPAH has not been well studied, the researchers said.

In a cross-sectional study published in CHEST, the researchers reviewed lung histology data from 50 adults with IPAH that had been assessed by two experienced pathologists. The mean age of the patients was 52 years and 58% were women. Based on a histopathologic evaluation, 24 patients had nonplexiform vasculopathy (48%) and 26 had plexiform vasculopathy (52%). Notably, microvascular remodeling involving arterioles and venules was substantial in patients with nonplexiform vasculopathy but mild or absent in those with plexiform vasculopathy, the researchers wrote.

The researchers also compared the clinical characteristics of patients with plexiform vs nonplexiform vasculopathy. Hemodynamic parameters were similar in both patient groups. However, those with nonplexiform vasculopathy were significantly older than those with plexiform vasculopathy (60 years vs 44 years), were more likely to be men (67% vs 20%), and had a lower diffusing capacity of the lungs for carbon monoxide (DLCO) at diagnosis (all P < .001). Patients with nonplexiform vasculopathy also were significantly more likely than those with plexiform vasculopathy to have a history of smoking (P = .03). Genetic testing revealed no mutations in established PAH genes in the nonplexiform group.

Low DLCO has been associated with worse outcomes regardless of hemodynamic response, the researchers noted. In the current study, “a DLCO of < 45% almost perfectly identified patients with nonplexiform vasculopathy with prominent pulmonary microvascular disease,” they said.

The findings were limited by several factors, including the small study population and the higher frequency of surgical lung biopsies in the nonplexiform group vs the plexiform group, which is not part of the general workup of patients with IPAH, the researchers noted.

More research is needed to better define the subgroup of patients with IPAH with nonplexiform vasculopathy and to identify the causes, biological features, and treatment approaches for these patients, they said. However, the results suggest that differences between patients with IPAH with plexiform vasculopathy and those with nonplexiform vasculopathy could ultimately inform targeted treatment strategies.

“Recognizing these clinical phenotypes allows revisiting current datasets to understand better the potential future clinical consequences of the vascular phenotypes for treatment response and clinical outcome,” the researchers concluded.
 

Findings May Inform More Targeted Therapy

“Any investigation that adds substantive insight into a complex disease that can translate into a better understanding of clinical patient phenotypes and eventually into improved treatments and patient outcomes has relevance at any time,” Paul Forfia, MD, professor of medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, said in an interview.

“There is focus on the antiproliferative forms of pulmonary arterial hypertension–specific therapy, and the results of the current study may have implications to these therapies,” said Dr. Forfia, who was not involved in the current study.

“In the current study, the investigators show that 48% of patients that were traditionally categorized as IPAH had a vascular phenotype that is not considered ‘typical’ or classic for IPAH,” Dr. Forfia told this news organization. “These findings highlight a significant heterogeneity of the pulmonary vascular phenotype within IPAH, which raises the question of whether the nonplexiform patient would be less responsive to the novel, antiproliferative forms of therapy,” he said.

The new findings are quite interesting but not surprising, Dr. Forfia said. “The World Symposia diagnostic groupings for pulmonary hypertension are a very important and necessary form of categorization and differentiation amongst forms of PH [pulmonary hypertension], and these groupings make a best attempt based on available evidence to separate patients of varying PH pathophysiology, both in terms of diagnosis and in how PH patients are treated,” he explained.

“However, clinical experts in PH have known that subphenotypes of PH pathophysiology exist within group I PAH, as well as in PH related to left heart disease (group 2), chronic respiratory disease (group 3), and chronic thromboembolic disease (group 4),” he said.

Findings from the current study reinforce the importance of clinical and physiological phenotyping of each patient, which can help in terms of therapy selection and in managing expectations in response to therapy, Dr. Forfia added.

“Perhaps the most evident and important clinical implication from the current study is to remind clinicians treating patients with PH that heterogeneity exists within the vascular phenotype and clinical makeup of patients even within the same type of PAH,” Dr. Forfia said. “With this insight, clinicians are more informed and thus more apt to consider nuances in the diagnosis, treatment, and expectations for treatment response within PAH,” he said.

Dr. Forfia also highlighted the potential implications of the association between cigarette smoking and the nonplexiform vascular phenotype. “This association was present in the absence of radiographic evidence of emphysema and raises the provocative notion that cigarette smoking may lead to pulmonary vascular abnormalities, perhaps even PAH, in patients without a diagnosis of emphysema,” he said.

“An important limitation from the current study is that the vascular phenotypes observed within their cohort of IPAH patients were obtained from histopathology specimens at the time of autopsy, explant at the time of lung transplantation, and surgical lung biopsy spanning over a 22-year period,” Dr. Forfia noted. Additional research is needed to explore how vascular phenotypic differences can be appreciated in the absence of histopathology and how these differences could impact therapy selection and patient outcomes, he said.

The study received no outside funding. Dr. Nossent disclosed receiving speaker fees from Janssen, MSD, and United Therapeutics/Ferrer and consulting fees from Janssen and United Therapeutics/Ferrer. Dr. Forfia had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Approximately half of adults with idiopathic pulmonary arterial hypertension (IPAH) had nonplexiform vasculopathy characterized in part by severe pulmonary microvascular remodeling, based on data from 50 individuals.

The clinical phenotype of IPAH was historically described as a rapidly progressive rare disease in young women and characterized by plexiform lesions, wrote Esther J. Nossent, MD, of Amsterdam University Medical Centers, Amsterdam, the Netherlands, and colleagues. However, the patient population with IPAH has become older and predominantly men, and the nature of vascular phenotypes and histologic patterns in patients with contemporary IPAH has not been well studied, the researchers said.

In a cross-sectional study published in CHEST, the researchers reviewed lung histology data from 50 adults with IPAH that had been assessed by two experienced pathologists. The mean age of the patients was 52 years and 58% were women. Based on a histopathologic evaluation, 24 patients had nonplexiform vasculopathy (48%) and 26 had plexiform vasculopathy (52%). Notably, microvascular remodeling involving arterioles and venules was substantial in patients with nonplexiform vasculopathy but mild or absent in those with plexiform vasculopathy, the researchers wrote.

The researchers also compared the clinical characteristics of patients with plexiform vs nonplexiform vasculopathy. Hemodynamic parameters were similar in both patient groups. However, those with nonplexiform vasculopathy were significantly older than those with plexiform vasculopathy (60 years vs 44 years), were more likely to be men (67% vs 20%), and had a lower diffusing capacity of the lungs for carbon monoxide (DLCO) at diagnosis (all P < .001). Patients with nonplexiform vasculopathy also were significantly more likely than those with plexiform vasculopathy to have a history of smoking (P = .03). Genetic testing revealed no mutations in established PAH genes in the nonplexiform group.

Low DLCO has been associated with worse outcomes regardless of hemodynamic response, the researchers noted. In the current study, “a DLCO of < 45% almost perfectly identified patients with nonplexiform vasculopathy with prominent pulmonary microvascular disease,” they said.

The findings were limited by several factors, including the small study population and the higher frequency of surgical lung biopsies in the nonplexiform group vs the plexiform group, which is not part of the general workup of patients with IPAH, the researchers noted.

More research is needed to better define the subgroup of patients with IPAH with nonplexiform vasculopathy and to identify the causes, biological features, and treatment approaches for these patients, they said. However, the results suggest that differences between patients with IPAH with plexiform vasculopathy and those with nonplexiform vasculopathy could ultimately inform targeted treatment strategies.

“Recognizing these clinical phenotypes allows revisiting current datasets to understand better the potential future clinical consequences of the vascular phenotypes for treatment response and clinical outcome,” the researchers concluded.
 

Findings May Inform More Targeted Therapy

“Any investigation that adds substantive insight into a complex disease that can translate into a better understanding of clinical patient phenotypes and eventually into improved treatments and patient outcomes has relevance at any time,” Paul Forfia, MD, professor of medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, said in an interview.

“There is focus on the antiproliferative forms of pulmonary arterial hypertension–specific therapy, and the results of the current study may have implications to these therapies,” said Dr. Forfia, who was not involved in the current study.

“In the current study, the investigators show that 48% of patients that were traditionally categorized as IPAH had a vascular phenotype that is not considered ‘typical’ or classic for IPAH,” Dr. Forfia told this news organization. “These findings highlight a significant heterogeneity of the pulmonary vascular phenotype within IPAH, which raises the question of whether the nonplexiform patient would be less responsive to the novel, antiproliferative forms of therapy,” he said.

The new findings are quite interesting but not surprising, Dr. Forfia said. “The World Symposia diagnostic groupings for pulmonary hypertension are a very important and necessary form of categorization and differentiation amongst forms of PH [pulmonary hypertension], and these groupings make a best attempt based on available evidence to separate patients of varying PH pathophysiology, both in terms of diagnosis and in how PH patients are treated,” he explained.

“However, clinical experts in PH have known that subphenotypes of PH pathophysiology exist within group I PAH, as well as in PH related to left heart disease (group 2), chronic respiratory disease (group 3), and chronic thromboembolic disease (group 4),” he said.

Findings from the current study reinforce the importance of clinical and physiological phenotyping of each patient, which can help in terms of therapy selection and in managing expectations in response to therapy, Dr. Forfia added.

“Perhaps the most evident and important clinical implication from the current study is to remind clinicians treating patients with PH that heterogeneity exists within the vascular phenotype and clinical makeup of patients even within the same type of PAH,” Dr. Forfia said. “With this insight, clinicians are more informed and thus more apt to consider nuances in the diagnosis, treatment, and expectations for treatment response within PAH,” he said.

Dr. Forfia also highlighted the potential implications of the association between cigarette smoking and the nonplexiform vascular phenotype. “This association was present in the absence of radiographic evidence of emphysema and raises the provocative notion that cigarette smoking may lead to pulmonary vascular abnormalities, perhaps even PAH, in patients without a diagnosis of emphysema,” he said.

“An important limitation from the current study is that the vascular phenotypes observed within their cohort of IPAH patients were obtained from histopathology specimens at the time of autopsy, explant at the time of lung transplantation, and surgical lung biopsy spanning over a 22-year period,” Dr. Forfia noted. Additional research is needed to explore how vascular phenotypic differences can be appreciated in the absence of histopathology and how these differences could impact therapy selection and patient outcomes, he said.

The study received no outside funding. Dr. Nossent disclosed receiving speaker fees from Janssen, MSD, and United Therapeutics/Ferrer and consulting fees from Janssen and United Therapeutics/Ferrer. Dr. Forfia had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Approximately half of adults with idiopathic pulmonary arterial hypertension (IPAH) had nonplexiform vasculopathy characterized in part by severe pulmonary microvascular remodeling, based on data from 50 individuals.

The clinical phenotype of IPAH was historically described as a rapidly progressive rare disease in young women and characterized by plexiform lesions, wrote Esther J. Nossent, MD, of Amsterdam University Medical Centers, Amsterdam, the Netherlands, and colleagues. However, the patient population with IPAH has become older and predominantly men, and the nature of vascular phenotypes and histologic patterns in patients with contemporary IPAH has not been well studied, the researchers said.

In a cross-sectional study published in CHEST, the researchers reviewed lung histology data from 50 adults with IPAH that had been assessed by two experienced pathologists. The mean age of the patients was 52 years and 58% were women. Based on a histopathologic evaluation, 24 patients had nonplexiform vasculopathy (48%) and 26 had plexiform vasculopathy (52%). Notably, microvascular remodeling involving arterioles and venules was substantial in patients with nonplexiform vasculopathy but mild or absent in those with plexiform vasculopathy, the researchers wrote.

The researchers also compared the clinical characteristics of patients with plexiform vs nonplexiform vasculopathy. Hemodynamic parameters were similar in both patient groups. However, those with nonplexiform vasculopathy were significantly older than those with plexiform vasculopathy (60 years vs 44 years), were more likely to be men (67% vs 20%), and had a lower diffusing capacity of the lungs for carbon monoxide (DLCO) at diagnosis (all P < .001). Patients with nonplexiform vasculopathy also were significantly more likely than those with plexiform vasculopathy to have a history of smoking (P = .03). Genetic testing revealed no mutations in established PAH genes in the nonplexiform group.

Low DLCO has been associated with worse outcomes regardless of hemodynamic response, the researchers noted. In the current study, “a DLCO of < 45% almost perfectly identified patients with nonplexiform vasculopathy with prominent pulmonary microvascular disease,” they said.

The findings were limited by several factors, including the small study population and the higher frequency of surgical lung biopsies in the nonplexiform group vs the plexiform group, which is not part of the general workup of patients with IPAH, the researchers noted.

More research is needed to better define the subgroup of patients with IPAH with nonplexiform vasculopathy and to identify the causes, biological features, and treatment approaches for these patients, they said. However, the results suggest that differences between patients with IPAH with plexiform vasculopathy and those with nonplexiform vasculopathy could ultimately inform targeted treatment strategies.

“Recognizing these clinical phenotypes allows revisiting current datasets to understand better the potential future clinical consequences of the vascular phenotypes for treatment response and clinical outcome,” the researchers concluded.
 

Findings May Inform More Targeted Therapy

“Any investigation that adds substantive insight into a complex disease that can translate into a better understanding of clinical patient phenotypes and eventually into improved treatments and patient outcomes has relevance at any time,” Paul Forfia, MD, professor of medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, said in an interview.

“There is focus on the antiproliferative forms of pulmonary arterial hypertension–specific therapy, and the results of the current study may have implications to these therapies,” said Dr. Forfia, who was not involved in the current study.

“In the current study, the investigators show that 48% of patients that were traditionally categorized as IPAH had a vascular phenotype that is not considered ‘typical’ or classic for IPAH,” Dr. Forfia told this news organization. “These findings highlight a significant heterogeneity of the pulmonary vascular phenotype within IPAH, which raises the question of whether the nonplexiform patient would be less responsive to the novel, antiproliferative forms of therapy,” he said.

The new findings are quite interesting but not surprising, Dr. Forfia said. “The World Symposia diagnostic groupings for pulmonary hypertension are a very important and necessary form of categorization and differentiation amongst forms of PH [pulmonary hypertension], and these groupings make a best attempt based on available evidence to separate patients of varying PH pathophysiology, both in terms of diagnosis and in how PH patients are treated,” he explained.

“However, clinical experts in PH have known that subphenotypes of PH pathophysiology exist within group I PAH, as well as in PH related to left heart disease (group 2), chronic respiratory disease (group 3), and chronic thromboembolic disease (group 4),” he said.

Findings from the current study reinforce the importance of clinical and physiological phenotyping of each patient, which can help in terms of therapy selection and in managing expectations in response to therapy, Dr. Forfia added.

“Perhaps the most evident and important clinical implication from the current study is to remind clinicians treating patients with PH that heterogeneity exists within the vascular phenotype and clinical makeup of patients even within the same type of PAH,” Dr. Forfia said. “With this insight, clinicians are more informed and thus more apt to consider nuances in the diagnosis, treatment, and expectations for treatment response within PAH,” he said.

Dr. Forfia also highlighted the potential implications of the association between cigarette smoking and the nonplexiform vascular phenotype. “This association was present in the absence of radiographic evidence of emphysema and raises the provocative notion that cigarette smoking may lead to pulmonary vascular abnormalities, perhaps even PAH, in patients without a diagnosis of emphysema,” he said.

“An important limitation from the current study is that the vascular phenotypes observed within their cohort of IPAH patients were obtained from histopathology specimens at the time of autopsy, explant at the time of lung transplantation, and surgical lung biopsy spanning over a 22-year period,” Dr. Forfia noted. Additional research is needed to explore how vascular phenotypic differences can be appreciated in the absence of histopathology and how these differences could impact therapy selection and patient outcomes, he said.

The study received no outside funding. Dr. Nossent disclosed receiving speaker fees from Janssen, MSD, and United Therapeutics/Ferrer and consulting fees from Janssen and United Therapeutics/Ferrer. Dr. Forfia had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Increased levels of the cytokine resistin were significantly associated with an increased risk for death in adults with pulmonary arterial hypertension (PAH), based on data from more than 1000 individuals.

Resistin, a cytokine expressed in adipocytes, has been associated with poor clinical outcomes in heart failure and cardiovascular disease, Li Gao, MD, of Johns Hopkins University, Baltimore, Maryland, and colleagues wrote. While mouse studies have shown that human resistin drives pulmonary vascular remodeling and the development of PAH, the role of resistin as a biomarker for PAH remains unclear.

In a study published in Respiratory Research, the researchers reviewed biospecimens and clinical and genetic data from 1121 adults with PAH, 808 with idiopathic PAH (IPAH), and 313 with scleroderma-associated PAH (SSc-PAH). They examined the associations between serum resistin levels and PAH outcomes in multivariate regression models, using machine-learning algorithms to develop models to predict mortality.

Resistin levels were significantly higher in all patients with PAH and patients with the two subtypes than in control participants (all P < .0001). Resistin was also associated with significant discriminative properties, with area under the curve (AUC) measures of 0.84, 0.82, and 0.91 for PAH overall, IPAH, and SSc-PAH, respectively.

Elevated resistin levels (defined as > 4.54 ng/mL) were significantly associated with an increased risk for death (hazard ratio, 2.6; P < .0087) as well as with older age and shorter distance on the 6-minute walk test (P = .001 for both) and reduced cardiac capacity based on the New York Heart Association functional class (P < .014).

Survival models derived from machine learning confirmed the prognostic value of resistin for mortality in PAH as seen in the random forest model, with an AUC of 0.70. “When we used the AUC values of the ROC curve as criteria to evaluate how well resistin levels discerned the presence of PAH, all three tests had excellent discriminative ability (AUCs were 0.84, 0.82, and 0.91 for all PAH, IPAH, and SSc-PAH, respectively),” the researchers wrote.

The researchers also evaluated three RETN genetic variants (rs7408174, rs3219175, and rs3745367) for a specific association with serum resistin levels and measures of PAH severity. Resistin levels were highest among individuals who were carriers of either the rs3219175 or rs3745367 mutation, the researchers noted.

The findings were limited by several factors, including missing data on the 6-minute walk test from several centers, which led to the elimination of that item from the survival analysis. Other limitations included the inability to control for PAH therapy at the time of assessment and the collection of serum at a different time from other clinical variables.

However, “our study provides evidence to support the use of circulating biomarkers as objective and accessible tools for noninvasive PAH risk stratification,” the researchers said. Additional research is needed to strengthen the association, but the findings suggest that resistin represents a novel biomarker for PAH prognostication and risk stratification and may have implications for the development of new treatments.
 

Biomarker Research Expands Diagnosis and Treatment Horizons

“It is a dynamic time in PAH research and clinical management, given the recent approval and use of the BMP/TGF beta balancing agent sotatercept (Winrevair) as an effective agent to target the molecular origins of this disease,” Stephen Chan, MD, professor of medicine and director of the Vascular Medicine Institute at the University of Pittsburgh, Pittsburgh, Pennsylvania, said in an interview.

The growing number of medications that can be used to treat patients with PAH will likely be more effective if patients are identified and treated early, said Dr. Chan, who was not involved in the study.

However, the time to diagnosis for patients with PAH is still more than 3 years from the start of symptoms, he said. Factors contributing to the delay include the requirement of an invasive cardiac catheterization procedure to make the final diagnosis, the status of PAH as a borderline orphan disease, and the often nonspecific nature of the initial symptoms of PAH.

Consequently, “there is an unmet need to develop effective and preferably noninvasive tools to aid in early diagnosis of PAH,” Dr. Chan added.

The power of the study is in the number of patients included, as much of previous PAH research has involved small studies of patients that could not be replicated or did not generalize to the larger patient population, Dr. Chan said.

The use of the PAH Biobank allows researchers to access a larger population of patients with PAH. “With that in mind, it is not surprising that some markers would emerge as potentially powerful and clinically meaningful,” he said.

“Currently, we do not have a reliable blood-based biomarker that we use in clinical PAH practice, although there are emerging studies that suggest other markers such as metabolites, RNA molecules, and proteins that may serve in the same capacity. If these studies turn out to be reproducible, generalizable, and specific to PAH in larger populations, measuring resistin could be helpful in making early diagnosis, particularly in areas that do not have invasive catheterization facilities (and globally) and for nonspecialists who are puzzled about the nonspecificity of initial symptoms of PAH,” Dr. Chan said.

Resistin could also be incorporated into existing risk stratification scores, such as the REVEAL risk score, that are already used in PAH clinical practice as guidance for when and how to use currently approved medications, he added.

Limitations of the study included the focus only on resistin alone, not in combination with other molecules that might perform better. Also, no independent validation cohort was used, he noted. “While PAH Biobank certainly offered larger numbers than we typically see, we would have to see validation in large independent cohorts for us to be convinced that measurements of resistin should be used in clinical practice.”

Resistin is not specific to PAH, which makes interpretation of the results more complicated, said Dr. Chan. “In this study, the authors used a smaller healthy control cohort of 50 patients as a comparison to their PAH cohort. However, they did not compare their PAH cohort with other cohorts that represent these other ‘resistin-relevant diseases’ and thus do not know whether they can distinguish PAH from any of these other diseases based on simply the resistin levels.” The frequency of comorbidities in patients with PAH, such as obesity, other inflammatory diseases, and cardiovascular disease, could confound the resistin levels.

The study was supported by the National Institutes of Health. Neither the researchers nor Dr. Chan had financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Increased levels of the cytokine resistin were significantly associated with an increased risk for death in adults with pulmonary arterial hypertension (PAH), based on data from more than 1000 individuals.

Resistin, a cytokine expressed in adipocytes, has been associated with poor clinical outcomes in heart failure and cardiovascular disease, Li Gao, MD, of Johns Hopkins University, Baltimore, Maryland, and colleagues wrote. While mouse studies have shown that human resistin drives pulmonary vascular remodeling and the development of PAH, the role of resistin as a biomarker for PAH remains unclear.

In a study published in Respiratory Research, the researchers reviewed biospecimens and clinical and genetic data from 1121 adults with PAH, 808 with idiopathic PAH (IPAH), and 313 with scleroderma-associated PAH (SSc-PAH). They examined the associations between serum resistin levels and PAH outcomes in multivariate regression models, using machine-learning algorithms to develop models to predict mortality.

Resistin levels were significantly higher in all patients with PAH and patients with the two subtypes than in control participants (all P < .0001). Resistin was also associated with significant discriminative properties, with area under the curve (AUC) measures of 0.84, 0.82, and 0.91 for PAH overall, IPAH, and SSc-PAH, respectively.

Elevated resistin levels (defined as > 4.54 ng/mL) were significantly associated with an increased risk for death (hazard ratio, 2.6; P < .0087) as well as with older age and shorter distance on the 6-minute walk test (P = .001 for both) and reduced cardiac capacity based on the New York Heart Association functional class (P < .014).

Survival models derived from machine learning confirmed the prognostic value of resistin for mortality in PAH as seen in the random forest model, with an AUC of 0.70. “When we used the AUC values of the ROC curve as criteria to evaluate how well resistin levels discerned the presence of PAH, all three tests had excellent discriminative ability (AUCs were 0.84, 0.82, and 0.91 for all PAH, IPAH, and SSc-PAH, respectively),” the researchers wrote.

The researchers also evaluated three RETN genetic variants (rs7408174, rs3219175, and rs3745367) for a specific association with serum resistin levels and measures of PAH severity. Resistin levels were highest among individuals who were carriers of either the rs3219175 or rs3745367 mutation, the researchers noted.

The findings were limited by several factors, including missing data on the 6-minute walk test from several centers, which led to the elimination of that item from the survival analysis. Other limitations included the inability to control for PAH therapy at the time of assessment and the collection of serum at a different time from other clinical variables.

However, “our study provides evidence to support the use of circulating biomarkers as objective and accessible tools for noninvasive PAH risk stratification,” the researchers said. Additional research is needed to strengthen the association, but the findings suggest that resistin represents a novel biomarker for PAH prognostication and risk stratification and may have implications for the development of new treatments.
 

Biomarker Research Expands Diagnosis and Treatment Horizons

“It is a dynamic time in PAH research and clinical management, given the recent approval and use of the BMP/TGF beta balancing agent sotatercept (Winrevair) as an effective agent to target the molecular origins of this disease,” Stephen Chan, MD, professor of medicine and director of the Vascular Medicine Institute at the University of Pittsburgh, Pittsburgh, Pennsylvania, said in an interview.

The growing number of medications that can be used to treat patients with PAH will likely be more effective if patients are identified and treated early, said Dr. Chan, who was not involved in the study.

However, the time to diagnosis for patients with PAH is still more than 3 years from the start of symptoms, he said. Factors contributing to the delay include the requirement of an invasive cardiac catheterization procedure to make the final diagnosis, the status of PAH as a borderline orphan disease, and the often nonspecific nature of the initial symptoms of PAH.

Consequently, “there is an unmet need to develop effective and preferably noninvasive tools to aid in early diagnosis of PAH,” Dr. Chan added.

The power of the study is in the number of patients included, as much of previous PAH research has involved small studies of patients that could not be replicated or did not generalize to the larger patient population, Dr. Chan said.

The use of the PAH Biobank allows researchers to access a larger population of patients with PAH. “With that in mind, it is not surprising that some markers would emerge as potentially powerful and clinically meaningful,” he said.

“Currently, we do not have a reliable blood-based biomarker that we use in clinical PAH practice, although there are emerging studies that suggest other markers such as metabolites, RNA molecules, and proteins that may serve in the same capacity. If these studies turn out to be reproducible, generalizable, and specific to PAH in larger populations, measuring resistin could be helpful in making early diagnosis, particularly in areas that do not have invasive catheterization facilities (and globally) and for nonspecialists who are puzzled about the nonspecificity of initial symptoms of PAH,” Dr. Chan said.

Resistin could also be incorporated into existing risk stratification scores, such as the REVEAL risk score, that are already used in PAH clinical practice as guidance for when and how to use currently approved medications, he added.

Limitations of the study included the focus only on resistin alone, not in combination with other molecules that might perform better. Also, no independent validation cohort was used, he noted. “While PAH Biobank certainly offered larger numbers than we typically see, we would have to see validation in large independent cohorts for us to be convinced that measurements of resistin should be used in clinical practice.”

Resistin is not specific to PAH, which makes interpretation of the results more complicated, said Dr. Chan. “In this study, the authors used a smaller healthy control cohort of 50 patients as a comparison to their PAH cohort. However, they did not compare their PAH cohort with other cohorts that represent these other ‘resistin-relevant diseases’ and thus do not know whether they can distinguish PAH from any of these other diseases based on simply the resistin levels.” The frequency of comorbidities in patients with PAH, such as obesity, other inflammatory diseases, and cardiovascular disease, could confound the resistin levels.

The study was supported by the National Institutes of Health. Neither the researchers nor Dr. Chan had financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Increased levels of the cytokine resistin were significantly associated with an increased risk for death in adults with pulmonary arterial hypertension (PAH), based on data from more than 1000 individuals.

Resistin, a cytokine expressed in adipocytes, has been associated with poor clinical outcomes in heart failure and cardiovascular disease, Li Gao, MD, of Johns Hopkins University, Baltimore, Maryland, and colleagues wrote. While mouse studies have shown that human resistin drives pulmonary vascular remodeling and the development of PAH, the role of resistin as a biomarker for PAH remains unclear.

In a study published in Respiratory Research, the researchers reviewed biospecimens and clinical and genetic data from 1121 adults with PAH, 808 with idiopathic PAH (IPAH), and 313 with scleroderma-associated PAH (SSc-PAH). They examined the associations between serum resistin levels and PAH outcomes in multivariate regression models, using machine-learning algorithms to develop models to predict mortality.

Resistin levels were significantly higher in all patients with PAH and patients with the two subtypes than in control participants (all P < .0001). Resistin was also associated with significant discriminative properties, with area under the curve (AUC) measures of 0.84, 0.82, and 0.91 for PAH overall, IPAH, and SSc-PAH, respectively.

Elevated resistin levels (defined as > 4.54 ng/mL) were significantly associated with an increased risk for death (hazard ratio, 2.6; P < .0087) as well as with older age and shorter distance on the 6-minute walk test (P = .001 for both) and reduced cardiac capacity based on the New York Heart Association functional class (P < .014).

Survival models derived from machine learning confirmed the prognostic value of resistin for mortality in PAH as seen in the random forest model, with an AUC of 0.70. “When we used the AUC values of the ROC curve as criteria to evaluate how well resistin levels discerned the presence of PAH, all three tests had excellent discriminative ability (AUCs were 0.84, 0.82, and 0.91 for all PAH, IPAH, and SSc-PAH, respectively),” the researchers wrote.

The researchers also evaluated three RETN genetic variants (rs7408174, rs3219175, and rs3745367) for a specific association with serum resistin levels and measures of PAH severity. Resistin levels were highest among individuals who were carriers of either the rs3219175 or rs3745367 mutation, the researchers noted.

The findings were limited by several factors, including missing data on the 6-minute walk test from several centers, which led to the elimination of that item from the survival analysis. Other limitations included the inability to control for PAH therapy at the time of assessment and the collection of serum at a different time from other clinical variables.

However, “our study provides evidence to support the use of circulating biomarkers as objective and accessible tools for noninvasive PAH risk stratification,” the researchers said. Additional research is needed to strengthen the association, but the findings suggest that resistin represents a novel biomarker for PAH prognostication and risk stratification and may have implications for the development of new treatments.
 

Biomarker Research Expands Diagnosis and Treatment Horizons

“It is a dynamic time in PAH research and clinical management, given the recent approval and use of the BMP/TGF beta balancing agent sotatercept (Winrevair) as an effective agent to target the molecular origins of this disease,” Stephen Chan, MD, professor of medicine and director of the Vascular Medicine Institute at the University of Pittsburgh, Pittsburgh, Pennsylvania, said in an interview.

The growing number of medications that can be used to treat patients with PAH will likely be more effective if patients are identified and treated early, said Dr. Chan, who was not involved in the study.

However, the time to diagnosis for patients with PAH is still more than 3 years from the start of symptoms, he said. Factors contributing to the delay include the requirement of an invasive cardiac catheterization procedure to make the final diagnosis, the status of PAH as a borderline orphan disease, and the often nonspecific nature of the initial symptoms of PAH.

Consequently, “there is an unmet need to develop effective and preferably noninvasive tools to aid in early diagnosis of PAH,” Dr. Chan added.

The power of the study is in the number of patients included, as much of previous PAH research has involved small studies of patients that could not be replicated or did not generalize to the larger patient population, Dr. Chan said.

The use of the PAH Biobank allows researchers to access a larger population of patients with PAH. “With that in mind, it is not surprising that some markers would emerge as potentially powerful and clinically meaningful,” he said.

“Currently, we do not have a reliable blood-based biomarker that we use in clinical PAH practice, although there are emerging studies that suggest other markers such as metabolites, RNA molecules, and proteins that may serve in the same capacity. If these studies turn out to be reproducible, generalizable, and specific to PAH in larger populations, measuring resistin could be helpful in making early diagnosis, particularly in areas that do not have invasive catheterization facilities (and globally) and for nonspecialists who are puzzled about the nonspecificity of initial symptoms of PAH,” Dr. Chan said.

Resistin could also be incorporated into existing risk stratification scores, such as the REVEAL risk score, that are already used in PAH clinical practice as guidance for when and how to use currently approved medications, he added.

Limitations of the study included the focus only on resistin alone, not in combination with other molecules that might perform better. Also, no independent validation cohort was used, he noted. “While PAH Biobank certainly offered larger numbers than we typically see, we would have to see validation in large independent cohorts for us to be convinced that measurements of resistin should be used in clinical practice.”

Resistin is not specific to PAH, which makes interpretation of the results more complicated, said Dr. Chan. “In this study, the authors used a smaller healthy control cohort of 50 patients as a comparison to their PAH cohort. However, they did not compare their PAH cohort with other cohorts that represent these other ‘resistin-relevant diseases’ and thus do not know whether they can distinguish PAH from any of these other diseases based on simply the resistin levels.” The frequency of comorbidities in patients with PAH, such as obesity, other inflammatory diseases, and cardiovascular disease, could confound the resistin levels.

The study was supported by the National Institutes of Health. Neither the researchers nor Dr. Chan had financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

A less favorable balance between physical activity (PA) and sitting time (ST) is associated with a higher risk for all-cause mortality.

METHODOLOGY:

• Researchers evaluated the association between PA and ST with the risk for mortality in 5836 middle-aged and older Australian adults (mean age, 56.4 years; 45% men) from the Australian Diabetes, Obesity and Lifestyle Study.
• The Physical Activity and Sitting Time Balance Index (PASTBI) was calculated by dividing the total duration of daily PA by the duration of daily ST.
• Participants were categorized into quartiles on the basis of their PASTBI score, ranging from low PA/high ST to high PA/low ST.
• The primary outcome was all-cause mortality.

TAKEAWAY:

• During a median follow-up time of 14.3 years, 885 (15%) all-cause deaths were reported.
• The risk for all-cause mortality was 47% higher in participants with lower engagement in PA and higher ST (low PASTBI) than those with higher engagement in PA and lower ST (high PASTBI; adjusted hazard ratio, 1.47; 95% confidence interval, 1.21-1.79).

IN PRACTICE:

“The utility of the PASTBI in identifying relationships with mortality risk further highlights the importance of achieving a healthier balance in the dual health behaviors of PA [physical activity] and ST [sitting time],” the authors wrote.

SOURCE:

The study was led by Roslin Botlero, MBBS, MPH, PhD, of the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia. It was published online in the American Journal of Preventive Medicine.

LIMITATIONS:

The study relied on self-reported data for PA and ST, which may have introduced recall or reporting bias. The generalizability of the findings is restricted to a specific set of self-reported questionnaires. Even after adjustment for several potential confounders, other unmeasured or unknown confounders may have influenced the association between PASTBI and all-cause mortality.
 

DISCLOSURES:

The Australian Diabetes, Obesity and Lifestyle Study was sponsored by the National Health and Medical Research Council, the Australian Government Department of Health and Aged Care, and others. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A less favorable balance between physical activity (PA) and sitting time (ST) is associated with a higher risk for all-cause mortality.

METHODOLOGY:

• Researchers evaluated the association between PA and ST with the risk for mortality in 5836 middle-aged and older Australian adults (mean age, 56.4 years; 45% men) from the Australian Diabetes, Obesity and Lifestyle Study.
• The Physical Activity and Sitting Time Balance Index (PASTBI) was calculated by dividing the total duration of daily PA by the duration of daily ST.
• Participants were categorized into quartiles on the basis of their PASTBI score, ranging from low PA/high ST to high PA/low ST.
• The primary outcome was all-cause mortality.

TAKEAWAY:

• During a median follow-up time of 14.3 years, 885 (15%) all-cause deaths were reported.
• The risk for all-cause mortality was 47% higher in participants with lower engagement in PA and higher ST (low PASTBI) than those with higher engagement in PA and lower ST (high PASTBI; adjusted hazard ratio, 1.47; 95% confidence interval, 1.21-1.79).

IN PRACTICE:

“The utility of the PASTBI in identifying relationships with mortality risk further highlights the importance of achieving a healthier balance in the dual health behaviors of PA [physical activity] and ST [sitting time],” the authors wrote.

SOURCE:

The study was led by Roslin Botlero, MBBS, MPH, PhD, of the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia. It was published online in the American Journal of Preventive Medicine.

LIMITATIONS:

The study relied on self-reported data for PA and ST, which may have introduced recall or reporting bias. The generalizability of the findings is restricted to a specific set of self-reported questionnaires. Even after adjustment for several potential confounders, other unmeasured or unknown confounders may have influenced the association between PASTBI and all-cause mortality.
 

DISCLOSURES:

The Australian Diabetes, Obesity and Lifestyle Study was sponsored by the National Health and Medical Research Council, the Australian Government Department of Health and Aged Care, and others. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A less favorable balance between physical activity (PA) and sitting time (ST) is associated with a higher risk for all-cause mortality.

METHODOLOGY:

• Researchers evaluated the association between PA and ST with the risk for mortality in 5836 middle-aged and older Australian adults (mean age, 56.4 years; 45% men) from the Australian Diabetes, Obesity and Lifestyle Study.
• The Physical Activity and Sitting Time Balance Index (PASTBI) was calculated by dividing the total duration of daily PA by the duration of daily ST.
• Participants were categorized into quartiles on the basis of their PASTBI score, ranging from low PA/high ST to high PA/low ST.
• The primary outcome was all-cause mortality.

TAKEAWAY:

• During a median follow-up time of 14.3 years, 885 (15%) all-cause deaths were reported.
• The risk for all-cause mortality was 47% higher in participants with lower engagement in PA and higher ST (low PASTBI) than those with higher engagement in PA and lower ST (high PASTBI; adjusted hazard ratio, 1.47; 95% confidence interval, 1.21-1.79).

IN PRACTICE:

“The utility of the PASTBI in identifying relationships with mortality risk further highlights the importance of achieving a healthier balance in the dual health behaviors of PA [physical activity] and ST [sitting time],” the authors wrote.

SOURCE:

The study was led by Roslin Botlero, MBBS, MPH, PhD, of the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia. It was published online in the American Journal of Preventive Medicine.

LIMITATIONS:

The study relied on self-reported data for PA and ST, which may have introduced recall or reporting bias. The generalizability of the findings is restricted to a specific set of self-reported questionnaires. Even after adjustment for several potential confounders, other unmeasured or unknown confounders may have influenced the association between PASTBI and all-cause mortality.
 

DISCLOSURES:

The Australian Diabetes, Obesity and Lifestyle Study was sponsored by the National Health and Medical Research Council, the Australian Government Department of Health and Aged Care, and others. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Very high and very low levels of high-density lipoprotein cholesterol (HDL-C) are linked to a higher risk for kidney disease in women with type 2 diabetes (T2D), but not in men.

METHODOLOGY:

• Studies have reported a strong association between low HDL-C levels and the risk for diabetic kidney disease, but whether higher HDL-C levels can influence the risk for diabetic kidney disease remains unclear.
• Researchers conducted a cross-sectional observational study of 936 patients with T2D (mean age, about 60 years; 41% women; 33% with diabetic kidney disease) from the Endocrinology Department at the Jinhua Hospital between September 2020 and July 2021.
• To examine the relationship between HDL-C levels and the risk for diabetic kidney disease, researchers used logistic regression to assess the continuous and categorical associations and a restricted cubic spline curve to assess the nonlinear association.
• HDL-C levels were categorized into four groups, with 0.40-0.96 mmol/L corresponding to the lowest quartile and 1.32-6.27 mmol/L corresponding to the highest quartile.
• The researchers observed a U-shaped association between HDL-C levels and the risk for diabetic kidney disease (P_nonlinear = .010) and selected two threshold values of 0.95 and 1.54 mmol/L.

TAKEAWAY:

• The risk for diabetic kidney disease was higher when the HDL-C levels were < 0.95 mmol/L or > 1.54 mmol/L.
• Compared with patients with HDL-C levels in the range of 0.95-1.54 mmol/L, those with very high and very low HDL-C levels had a 128% and 77% increased risk for diabetic kidney disease, respectively.
• The association was significant in women (P = .006) and not in men (P = .054), after adjusting for confounding factors.
• HDL-C level as a continuous variable was not associated with the risk for kidney disease (P = .902).

IN PRACTICE:

“Although HDL-C is generally considered a cardiovascular protective factor, at very high levels, this protective effect does not seem to hold true and may be associated with an increased DKD [diabetic kidney disease] risk,” the authors wrote.

SOURCE:

This study was led by Huabin Wang, from the Department of Clinical Laboratory, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China, and was published online in Scientific Reports.

LIMITATIONS:

The cross-sectional nature of the study limited the ability to establish a causal relationship between high HDL-C levels and the risk for diabetic kidney disease. The sample size of the study was relatively small at the higher end of the HDL-C concentration spectrum. Moreover, the study did not consider other potential confounding factors such as diet, sedentary lifestyle, obesity, genetic diseases, drug effects on HDL-C levels, and fluctuating estrogen levels, which could affect the overall findings.

DISCLOSURES:

The study was funded by the Department of Science and Technology of Zhejiang Province, China, and The Science and Technology Bureau of Jinhua City. The authors declared no competing interests.

A version of this article first appeared on Medscape.com.

TOPLINE:

Very high and very low levels of high-density lipoprotein cholesterol (HDL-C) are linked to a higher risk for kidney disease in women with type 2 diabetes (T2D), but not in men.

METHODOLOGY:

• Studies have reported a strong association between low HDL-C levels and the risk for diabetic kidney disease, but whether higher HDL-C levels can influence the risk for diabetic kidney disease remains unclear.
• Researchers conducted a cross-sectional observational study of 936 patients with T2D (mean age, about 60 years; 41% women; 33% with diabetic kidney disease) from the Endocrinology Department at the Jinhua Hospital between September 2020 and July 2021.
• To examine the relationship between HDL-C levels and the risk for diabetic kidney disease, researchers used logistic regression to assess the continuous and categorical associations and a restricted cubic spline curve to assess the nonlinear association.
• HDL-C levels were categorized into four groups, with 0.40-0.96 mmol/L corresponding to the lowest quartile and 1.32-6.27 mmol/L corresponding to the highest quartile.
• The researchers observed a U-shaped association between HDL-C levels and the risk for diabetic kidney disease (P_nonlinear = .010) and selected two threshold values of 0.95 and 1.54 mmol/L.

TAKEAWAY:

• The risk for diabetic kidney disease was higher when the HDL-C levels were < 0.95 mmol/L or > 1.54 mmol/L.
• Compared with patients with HDL-C levels in the range of 0.95-1.54 mmol/L, those with very high and very low HDL-C levels had a 128% and 77% increased risk for diabetic kidney disease, respectively.
• The association was significant in women (P = .006) and not in men (P = .054), after adjusting for confounding factors.
• HDL-C level as a continuous variable was not associated with the risk for kidney disease (P = .902).

IN PRACTICE:

“Although HDL-C is generally considered a cardiovascular protective factor, at very high levels, this protective effect does not seem to hold true and may be associated with an increased DKD [diabetic kidney disease] risk,” the authors wrote.

SOURCE:

This study was led by Huabin Wang, from the Department of Clinical Laboratory, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China, and was published online in Scientific Reports.

LIMITATIONS:

The cross-sectional nature of the study limited the ability to establish a causal relationship between high HDL-C levels and the risk for diabetic kidney disease. The sample size of the study was relatively small at the higher end of the HDL-C concentration spectrum. Moreover, the study did not consider other potential confounding factors such as diet, sedentary lifestyle, obesity, genetic diseases, drug effects on HDL-C levels, and fluctuating estrogen levels, which could affect the overall findings.

DISCLOSURES:

The study was funded by the Department of Science and Technology of Zhejiang Province, China, and The Science and Technology Bureau of Jinhua City. The authors declared no competing interests.

A version of this article first appeared on Medscape.com.

TOPLINE:

Very high and very low levels of high-density lipoprotein cholesterol (HDL-C) are linked to a higher risk for kidney disease in women with type 2 diabetes (T2D), but not in men.

METHODOLOGY:

• Studies have reported a strong association between low HDL-C levels and the risk for diabetic kidney disease, but whether higher HDL-C levels can influence the risk for diabetic kidney disease remains unclear.
• Researchers conducted a cross-sectional observational study of 936 patients with T2D (mean age, about 60 years; 41% women; 33% with diabetic kidney disease) from the Endocrinology Department at the Jinhua Hospital between September 2020 and July 2021.
• To examine the relationship between HDL-C levels and the risk for diabetic kidney disease, researchers used logistic regression to assess the continuous and categorical associations and a restricted cubic spline curve to assess the nonlinear association.
• HDL-C levels were categorized into four groups, with 0.40-0.96 mmol/L corresponding to the lowest quartile and 1.32-6.27 mmol/L corresponding to the highest quartile.
• The researchers observed a U-shaped association between HDL-C levels and the risk for diabetic kidney disease (P_nonlinear = .010) and selected two threshold values of 0.95 and 1.54 mmol/L.

TAKEAWAY:

• The risk for diabetic kidney disease was higher when the HDL-C levels were < 0.95 mmol/L or > 1.54 mmol/L.
• Compared with patients with HDL-C levels in the range of 0.95-1.54 mmol/L, those with very high and very low HDL-C levels had a 128% and 77% increased risk for diabetic kidney disease, respectively.
• The association was significant in women (P = .006) and not in men (P = .054), after adjusting for confounding factors.
• HDL-C level as a continuous variable was not associated with the risk for kidney disease (P = .902).

IN PRACTICE:

“Although HDL-C is generally considered a cardiovascular protective factor, at very high levels, this protective effect does not seem to hold true and may be associated with an increased DKD [diabetic kidney disease] risk,” the authors wrote.

SOURCE:

This study was led by Huabin Wang, from the Department of Clinical Laboratory, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China, and was published online in Scientific Reports.

LIMITATIONS:

The cross-sectional nature of the study limited the ability to establish a causal relationship between high HDL-C levels and the risk for diabetic kidney disease. The sample size of the study was relatively small at the higher end of the HDL-C concentration spectrum. Moreover, the study did not consider other potential confounding factors such as diet, sedentary lifestyle, obesity, genetic diseases, drug effects on HDL-C levels, and fluctuating estrogen levels, which could affect the overall findings.

DISCLOSURES:

The study was funded by the Department of Science and Technology of Zhejiang Province, China, and The Science and Technology Bureau of Jinhua City. The authors declared no competing interests.

A version of this article first appeared on Medscape.com.

Recently, a patient of mine was hospitalized with chest pain. She was diagnosed with an acute coronary syndrome and started on a statin in addition to a beta-blocker, aspirin, and clopidogrel. After discharge, she had symptoms of dizziness and recurrent chest pain and her first thought was to stop the statin because she believed that her symptoms were statin-related side effects. I will cover a few areas where I think that there are some misunderstandings about statins.

Statins Are Not Bad For the Liver

When lovastatin first became available for prescription in the 1980s, frequent monitoring of transaminases was recommended. Patients and healthcare professionals became accustomed to frequent liver tests to monitor for statin toxicity, and to this day, some healthcare professionals still obtain liver function tests for this purpose.

But is there a reason to do this? Pfeffer and colleagues reported on the results of over 112,000 people enrolled in the West of Scotland Coronary Protection trial and found that the percentage of patients with any abnormal liver function test was similar (> 3 times the upper limit of normal for ALT) for patients taking pravastatin (1.4%) and for patients taking placebo (1.4%).¹ A panel of liver experts concurred that statin-associated transaminase elevations were not indicative of liver damage or dysfunction.² Furthermore, they noted that chronic liver disease and compensated cirrhosis were not contraindications to statin use.

In a small study, use of low-dose atorvastatin in patients with nonalcoholic steatohepatitis improved transaminase values in 75% of patients and liver steatosis and nonalcoholic fatty liver disease activity scores were significantly improved on biopsy in most of the patients.³ The US Food and Drug Administration (FDA) removed the recommendation for routine regular monitoring of liver function for patients on statins in 2012.⁴

Statins Do Not Cause Muscle Pain in Most Patients

Most muscle pain occurring in patients on statins is not due to the statin although patient concerns about muscle pain are common. In a meta-analysis of 19 large statin trials, 27.1% of participants treated with a statin reported at least one episode of muscle pain or weakness during a median of 4.3 years, compared with 26.6% of participants treated with placebo.⁵ Muscle pain for any reason is common, and patients on statins may stop therapy because of the symptoms.

Cohen and colleagues performed a survey of past and current statin users, asking about muscle symptoms.⁶ Muscle-related side effects were reported by 60% of former statin users and 25% of current users.

Herrett and colleagues performed an extensive series of n-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.⁷ Participants received either 2-month blocks of atorvastatin 20 mg or 2-month blocks of placebo, six times. They rated their muscle symptoms on a visual analogue scale at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further when they planned an n-of-1 trial that included statin, placebo, and no treatment.⁸ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on a random sequence and reported daily symptom scores. The mean symptom intensity score was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).
 

Statins Are Likely Helpful In the Very Elderly

Should we be using statins for primary prevention in our very old patients? For many years the answer was generally “no” on the basis of a lack of evidence. Patients in their 80s often were not included in clinical trials. The much used American Heart Association risk calculator stops at age 79. Given the prevalence of coronary artery disease in patients as they reach their 80s, wouldn’t primary prevention really be secondary prevention? Xu and colleagues in a recent study compared outcomes for patients who were treated with statins for primary prevention with a group who were not. In the patients aged 75-84 there was a risk reduction for major cardiovascular events of 1.2% over 5 years, and for those 85 and older the risk reduction was 4.4%. Importantly, there were no significantly increased risks for myopathies and liver dysfunction in either age group.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Pfeffer MA et al. Circulation. 2002;105(20):2341-6.

2. Cohen DE et al. Am J Cardiol. 2006;97(8A):77C-81C.

3. Hyogo H et al. Metabolism. 2008;57(12):1711-8.

4. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012 Feb 28.

5. Cholesterol Treatment Trialists’ Collaboration. Lancet. 2022;400(10355):832-45.

6. Cohen JD et al. J Clin Lipidol. 2012;6(3):208-15.

7. Herrett E et al. BMJ. 2021 Feb 24;372:n1355.

8. Wood FA et al. N Engl J Med. 2020;383(22):2182-4.

9. Xu W et al. Ann Intern Med. 2024;177(6):701-10.

Recently, a patient of mine was hospitalized with chest pain. She was diagnosed with an acute coronary syndrome and started on a statin in addition to a beta-blocker, aspirin, and clopidogrel. After discharge, she had symptoms of dizziness and recurrent chest pain and her first thought was to stop the statin because she believed that her symptoms were statin-related side effects. I will cover a few areas where I think that there are some misunderstandings about statins.

Statins Are Not Bad For the Liver

When lovastatin first became available for prescription in the 1980s, frequent monitoring of transaminases was recommended. Patients and healthcare professionals became accustomed to frequent liver tests to monitor for statin toxicity, and to this day, some healthcare professionals still obtain liver function tests for this purpose.

But is there a reason to do this? Pfeffer and colleagues reported on the results of over 112,000 people enrolled in the West of Scotland Coronary Protection trial and found that the percentage of patients with any abnormal liver function test was similar (> 3 times the upper limit of normal for ALT) for patients taking pravastatin (1.4%) and for patients taking placebo (1.4%).¹ A panel of liver experts concurred that statin-associated transaminase elevations were not indicative of liver damage or dysfunction.² Furthermore, they noted that chronic liver disease and compensated cirrhosis were not contraindications to statin use.

In a small study, use of low-dose atorvastatin in patients with nonalcoholic steatohepatitis improved transaminase values in 75% of patients and liver steatosis and nonalcoholic fatty liver disease activity scores were significantly improved on biopsy in most of the patients.³ The US Food and Drug Administration (FDA) removed the recommendation for routine regular monitoring of liver function for patients on statins in 2012.⁴

Statins Do Not Cause Muscle Pain in Most Patients

Most muscle pain occurring in patients on statins is not due to the statin although patient concerns about muscle pain are common. In a meta-analysis of 19 large statin trials, 27.1% of participants treated with a statin reported at least one episode of muscle pain or weakness during a median of 4.3 years, compared with 26.6% of participants treated with placebo.⁵ Muscle pain for any reason is common, and patients on statins may stop therapy because of the symptoms.

Cohen and colleagues performed a survey of past and current statin users, asking about muscle symptoms.⁶ Muscle-related side effects were reported by 60% of former statin users and 25% of current users.

Herrett and colleagues performed an extensive series of n-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.⁷ Participants received either 2-month blocks of atorvastatin 20 mg or 2-month blocks of placebo, six times. They rated their muscle symptoms on a visual analogue scale at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further when they planned an n-of-1 trial that included statin, placebo, and no treatment.⁸ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on a random sequence and reported daily symptom scores. The mean symptom intensity score was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).
 

Statins Are Likely Helpful In the Very Elderly

Should we be using statins for primary prevention in our very old patients? For many years the answer was generally “no” on the basis of a lack of evidence. Patients in their 80s often were not included in clinical trials. The much used American Heart Association risk calculator stops at age 79. Given the prevalence of coronary artery disease in patients as they reach their 80s, wouldn’t primary prevention really be secondary prevention? Xu and colleagues in a recent study compared outcomes for patients who were treated with statins for primary prevention with a group who were not. In the patients aged 75-84 there was a risk reduction for major cardiovascular events of 1.2% over 5 years, and for those 85 and older the risk reduction was 4.4%. Importantly, there were no significantly increased risks for myopathies and liver dysfunction in either age group.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Pfeffer MA et al. Circulation. 2002;105(20):2341-6.

2. Cohen DE et al. Am J Cardiol. 2006;97(8A):77C-81C.

3. Hyogo H et al. Metabolism. 2008;57(12):1711-8.

4. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012 Feb 28.

5. Cholesterol Treatment Trialists’ Collaboration. Lancet. 2022;400(10355):832-45.

6. Cohen JD et al. J Clin Lipidol. 2012;6(3):208-15.

7. Herrett E et al. BMJ. 2021 Feb 24;372:n1355.

8. Wood FA et al. N Engl J Med. 2020;383(22):2182-4.

9. Xu W et al. Ann Intern Med. 2024;177(6):701-10.

Recently, a patient of mine was hospitalized with chest pain. She was diagnosed with an acute coronary syndrome and started on a statin in addition to a beta-blocker, aspirin, and clopidogrel. After discharge, she had symptoms of dizziness and recurrent chest pain and her first thought was to stop the statin because she believed that her symptoms were statin-related side effects. I will cover a few areas where I think that there are some misunderstandings about statins.

Statins Are Not Bad For the Liver

When lovastatin first became available for prescription in the 1980s, frequent monitoring of transaminases was recommended. Patients and healthcare professionals became accustomed to frequent liver tests to monitor for statin toxicity, and to this day, some healthcare professionals still obtain liver function tests for this purpose.

But is there a reason to do this? Pfeffer and colleagues reported on the results of over 112,000 people enrolled in the West of Scotland Coronary Protection trial and found that the percentage of patients with any abnormal liver function test was similar (> 3 times the upper limit of normal for ALT) for patients taking pravastatin (1.4%) and for patients taking placebo (1.4%).¹ A panel of liver experts concurred that statin-associated transaminase elevations were not indicative of liver damage or dysfunction.² Furthermore, they noted that chronic liver disease and compensated cirrhosis were not contraindications to statin use.

In a small study, use of low-dose atorvastatin in patients with nonalcoholic steatohepatitis improved transaminase values in 75% of patients and liver steatosis and nonalcoholic fatty liver disease activity scores were significantly improved on biopsy in most of the patients.³ The US Food and Drug Administration (FDA) removed the recommendation for routine regular monitoring of liver function for patients on statins in 2012.⁴

Statins Do Not Cause Muscle Pain in Most Patients

Most muscle pain occurring in patients on statins is not due to the statin although patient concerns about muscle pain are common. In a meta-analysis of 19 large statin trials, 27.1% of participants treated with a statin reported at least one episode of muscle pain or weakness during a median of 4.3 years, compared with 26.6% of participants treated with placebo.⁵ Muscle pain for any reason is common, and patients on statins may stop therapy because of the symptoms.

Cohen and colleagues performed a survey of past and current statin users, asking about muscle symptoms.⁶ Muscle-related side effects were reported by 60% of former statin users and 25% of current users.

Herrett and colleagues performed an extensive series of n-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.⁷ Participants received either 2-month blocks of atorvastatin 20 mg or 2-month blocks of placebo, six times. They rated their muscle symptoms on a visual analogue scale at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further when they planned an n-of-1 trial that included statin, placebo, and no treatment.⁸ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on a random sequence and reported daily symptom scores. The mean symptom intensity score was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).
 

Statins Are Likely Helpful In the Very Elderly

Should we be using statins for primary prevention in our very old patients? For many years the answer was generally “no” on the basis of a lack of evidence. Patients in their 80s often were not included in clinical trials. The much used American Heart Association risk calculator stops at age 79. Given the prevalence of coronary artery disease in patients as they reach their 80s, wouldn’t primary prevention really be secondary prevention? Xu and colleagues in a recent study compared outcomes for patients who were treated with statins for primary prevention with a group who were not. In the patients aged 75-84 there was a risk reduction for major cardiovascular events of 1.2% over 5 years, and for those 85 and older the risk reduction was 4.4%. Importantly, there were no significantly increased risks for myopathies and liver dysfunction in either age group.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Pfeffer MA et al. Circulation. 2002;105(20):2341-6.

2. Cohen DE et al. Am J Cardiol. 2006;97(8A):77C-81C.

3. Hyogo H et al. Metabolism. 2008;57(12):1711-8.

4. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012 Feb 28.

5. Cholesterol Treatment Trialists’ Collaboration. Lancet. 2022;400(10355):832-45.

6. Cohen JD et al. J Clin Lipidol. 2012;6(3):208-15.

7. Herrett E et al. BMJ. 2021 Feb 24;372:n1355.

8. Wood FA et al. N Engl J Med. 2020;383(22):2182-4.

9. Xu W et al. Ann Intern Med. 2024;177(6):701-10.

Jordan Stohler, a 42-year-old nurse in Knoxville, Tennessee, was readmitted to Fort Sanders Medical Center in June 2023 with sepsis after a double mastectomy. 

She spent 5 days in the hospital after surgery to clear up the infection. Then she was offered a choice: She could either stay in the hospital while she received IV antibiotics, or she could go home and have the antibiotics given to her there under the Advanced Care at Home program of Covenant Health, the nine-hospital system to which Fort Sanders belongs.

She opted to go home, where she knew she’d be more comfortable and would be close to her beloved dog. In the end, she was very glad she did. 

“I received great care in the hospital, but to be allowed to be in the comfort of your own home, to be around my dog, who I think is therapeutic, to be able to cook my own meals, and to have the same one-on-one nursing care that I would have gotten in the hospital was great,” Ms. Stohler said. “

Being cared for at home helped her heal, she said. “I probably would have gotten a little stir crazy if I’d stayed in the hospital any longer. I received excellent care at home.”

Covenant’s Advanced Care at Home program is an example of the hospital-at-home trend that has been growing rapidly since Medicare began reimbursing hospitals for this approach during the COVID pandemic. Currently, 322 hospitals in 37 states have Medicare waivers for these kinds of programs, although not all of them are currently functioning.

A recent survey published in JAMA found that nearly half of consumers would accept hospital-at-home, and more than a third were neutral on it. Only 17% said they’d rather be cared for in a brick-and-mortar hospital. 

The findings of the JAMA survey confirm those of earlier studies, said Bruce Leff, MD, a professor at Johns Hopkins Medical School in Baltimore, who has researched hospital-at-home since the 1990s. Like the new study, those trials found that the results had no relationship to individual traits, such as socioeconomic status, medical conditions, age, gender, or race. 

Whether a person felt comfortable with the idea of hospital-at-home boiled down “to a preference for receiving care at home or in the hospital,” he said. Some people distrust hospitals, and others feel insecure about receiving care at home, even if it is provided by qualified health care professionals.
 

How Patients Are Selected 

While the details of hospital-at-home vary from program to program, the basic scenario is that patients who need certain kinds of acute care can be sent home from hospitals, emergency departments, or clinics to receive that care at home. Among the kinds of conditions that make stable patients eligible are heart failure, COPD, pneumonia, cellulitis, and COVID-19, said John Busigin, MD, a hospitalist and medical director of Covenant Advanced Care at Home. 

When a patient is admitted to hospital-at-home, the hospital will send along whatever equipment and medications that person needs. In some cases, this may include a hospital bed, although Ms. Stohler used her own. An IV line was put into her arm, and the IV stand was placed next to the bed. 

Ms. Stohler received a computer tablet that she used to communicate with doctors and nurses in Covenant’s “command center” in Knoxville. She also wore a watch with a button she could push in case of an emergency. And she had a telephone line that went directly to her medical team, in case she had an issue and the tablet didn’t work.

Twice a day, or as needed, specially trained paramedics came to Ms. Stohler’s home. They checked on the IV line, changed the IV bag, performed tests, and uploaded vital signs from monitoring equipment to Ms. Stohler’s tablet so it could be transmitted to the command center. A physician assistant came in on the second and fourth days of her weeklong stay in the program, and she saw a hospitalist remotely every day.

While some hospital-at-home programs have registered nurses visit patients at home, RNs are in short supply. To fill this gap, Covenant’s program uses community paramedics who have been in the field for at least 5 years, doing everything from intubating patients and placing them on ventilators to providing advanced cardiac life support, Dr. Busigin said. To get certified as community paramedics, they go through a 3-month training program.

Shortly after Ms. Stohler went into hospital-at-home, she had another crisis. Excess fluid had built up in her body because of all the IV fluids she’d received in the hospital while fighting the sepsis. As a result, she became short of breath. If she had been discharged to home rather than hospital-at-home, she said, she would have had to go to the emergency room. Instead, she sent out a distress call. One of the paramedics rushed to her house and gave her an IV diuretic medication, which helped her urinate to get rid of the excess fluid.

A small number of the estimated 300 people who have gone through the program had to be admitted to the hospital, Dr. Busigin said. Nationally, he said, about 5%-10% are admitted. But readmissions among the patients in the Covenant program have been 25% lower than for patients who received conventional hospital care and had the same conditions as those in hospital-at-home.

Studies have shown that these programs not only reduce readmissions, but also cost less, on average, and create a better patient experience than traditional hospital care does. And, according to the JAMA survey, most consumers like the idea. Fifty-six percent of people who took the survey agreed with the statement that people recover faster at home than in the hospital. Fifty-nine percent agreed they’d feel safe being treated at home, and 49% said they’d be more comfortable if treated at home. 

The 1134 people who took the survey were also asked about their comfort level with providing various kinds of care to their loved ones during a hospital-at-home episode. The results varied with the type of task: For example, 82% of the respondents agreed or strongly agreed they could manage a patient’s medications, while just 41% said they’d be willing to change a feeding tube. Smaller percentages were willing to change an IV bag or a catheter or do wound care.

However, hospital-at-home programs don’t allow caregivers to take part in clinical care, which is prohibited by Medicare waivers and state licensing regulations. None of the 22 health systems that use the hospital-at-home services of Medically Home, including Covenant, ask caregivers to do anything along this line, said Pippa Shulman, DO, medical director of the company, which provides equipment, technology, and protocols for hospital programs

The only exception at Covenant, Dr. Busigin said, is that the hospital may train family members to do wound care when a patient is discharged from the hospital to Advanced Care at Home. They may also prepare meals for their loved ones, although the program provides balanced meals to patients if they want them. Ms. Stohler had some of these meals, which just had to be heated up, for the first few days of hospital-at-home, and later her relatives brought meals to her house.
 

Challenges for the Future

The number of Medicare hospital-at-home waivers has nearly doubled since 2021. A year earlier, when Medicare began reimbursing hospitals for acute care at home to help them cope with the overflow of COVID patients, there were only about 15-20 programs in the United States, said Dr. Leff of Johns Hopkins.

A big reason for the lack of use before the pandemic, Dr. Leff said, is that there was no payment system for hospitals that offered hospital-at-home. Now, they can get paid by Medicare and 10 state Medicaid programs, and a number of private payers are also coming on board. Ms. Stohler’s private insurer covered her hospital-at-home stay, and Dr. Busigin said several plans that contract with Covenant will pay for it.

Dr. Leff said he’s cautiously optimistic Congress will extend the Medicare waiver program, which is scheduled to end in December, for another 5 years. A couple of key House committees have signed off on a bill to do that, he said, and a Congressional Budget Office report found that the program did not cost Medicare more money. 

But even if the waiver is renewed, some health systems may find it tough to deliver the service. The current version of this model depends a lot on technology, because telemedicine is used and reliable communication is needed for patients in hospital-at-home. That’s why many of the hospitals hire outside vendors like Medically Home to provide the infrastructure they need.

Medically Home manages the tablets given to patients and all connection and networking services, including internet and cellphone connections. It also provides technical services in the command centers that hospitals set up for the doctors and nurses who provide care remotely. 

And the firm figures out how to deliver the standard care for each condition in each hospital-at-home. “We need to make sure that the patient is going to get what they need in the time frame it needs to be delivered in, and that it’s safe and effective for the patient,” Dr. Shulman said. “So we’ve developed logistical protocols for a multitude of disease states that allow us to provide high-acuity care in the home to a variety of complex patients.”

The health care workers use the hospital electronic health record for hospital-at-home patients, and vital signs uploaded from patient tablets flow directly into the electronic health record, she said.
 

Rural Areas Need Help

The use of hospital-at-home in rural areas holds a lot of promise, Dr. Leff said. 

“A lot of rural hospitals have been closing, and hospital-at-home could be a mechanism to create hospital-level care where facilities have closed down. It’s easier to do this in urban areas, but it can be done in rural environments as well.”

Rami Karjian, CEO of Medically Home, agreed. The firm services hospital-at-home programs in rural areas of Oklahoma and California, using cellphones and paramedics in areas that lack broadband connections and nurses, he pointed out. 

“Hospital-at-home can’t just be available to people who live in big cities,” he said. “The access problems in health care are pervasive, and this is part of how we solve access problems in rural areas.”
 

A version of this article first appeared on WebMD.com.

Jordan Stohler, a 42-year-old nurse in Knoxville, Tennessee, was readmitted to Fort Sanders Medical Center in June 2023 with sepsis after a double mastectomy. 

She spent 5 days in the hospital after surgery to clear up the infection. Then she was offered a choice: She could either stay in the hospital while she received IV antibiotics, or she could go home and have the antibiotics given to her there under the Advanced Care at Home program of Covenant Health, the nine-hospital system to which Fort Sanders belongs.

She opted to go home, where she knew she’d be more comfortable and would be close to her beloved dog. In the end, she was very glad she did. 

“I received great care in the hospital, but to be allowed to be in the comfort of your own home, to be around my dog, who I think is therapeutic, to be able to cook my own meals, and to have the same one-on-one nursing care that I would have gotten in the hospital was great,” Ms. Stohler said. “

Being cared for at home helped her heal, she said. “I probably would have gotten a little stir crazy if I’d stayed in the hospital any longer. I received excellent care at home.”

Covenant’s Advanced Care at Home program is an example of the hospital-at-home trend that has been growing rapidly since Medicare began reimbursing hospitals for this approach during the COVID pandemic. Currently, 322 hospitals in 37 states have Medicare waivers for these kinds of programs, although not all of them are currently functioning.

A recent survey published in JAMA found that nearly half of consumers would accept hospital-at-home, and more than a third were neutral on it. Only 17% said they’d rather be cared for in a brick-and-mortar hospital. 

The findings of the JAMA survey confirm those of earlier studies, said Bruce Leff, MD, a professor at Johns Hopkins Medical School in Baltimore, who has researched hospital-at-home since the 1990s. Like the new study, those trials found that the results had no relationship to individual traits, such as socioeconomic status, medical conditions, age, gender, or race. 

Whether a person felt comfortable with the idea of hospital-at-home boiled down “to a preference for receiving care at home or in the hospital,” he said. Some people distrust hospitals, and others feel insecure about receiving care at home, even if it is provided by qualified health care professionals.
 

How Patients Are Selected 

While the details of hospital-at-home vary from program to program, the basic scenario is that patients who need certain kinds of acute care can be sent home from hospitals, emergency departments, or clinics to receive that care at home. Among the kinds of conditions that make stable patients eligible are heart failure, COPD, pneumonia, cellulitis, and COVID-19, said John Busigin, MD, a hospitalist and medical director of Covenant Advanced Care at Home. 

When a patient is admitted to hospital-at-home, the hospital will send along whatever equipment and medications that person needs. In some cases, this may include a hospital bed, although Ms. Stohler used her own. An IV line was put into her arm, and the IV stand was placed next to the bed. 

Ms. Stohler received a computer tablet that she used to communicate with doctors and nurses in Covenant’s “command center” in Knoxville. She also wore a watch with a button she could push in case of an emergency. And she had a telephone line that went directly to her medical team, in case she had an issue and the tablet didn’t work.

Twice a day, or as needed, specially trained paramedics came to Ms. Stohler’s home. They checked on the IV line, changed the IV bag, performed tests, and uploaded vital signs from monitoring equipment to Ms. Stohler’s tablet so it could be transmitted to the command center. A physician assistant came in on the second and fourth days of her weeklong stay in the program, and she saw a hospitalist remotely every day.

While some hospital-at-home programs have registered nurses visit patients at home, RNs are in short supply. To fill this gap, Covenant’s program uses community paramedics who have been in the field for at least 5 years, doing everything from intubating patients and placing them on ventilators to providing advanced cardiac life support, Dr. Busigin said. To get certified as community paramedics, they go through a 3-month training program.

Shortly after Ms. Stohler went into hospital-at-home, she had another crisis. Excess fluid had built up in her body because of all the IV fluids she’d received in the hospital while fighting the sepsis. As a result, she became short of breath. If she had been discharged to home rather than hospital-at-home, she said, she would have had to go to the emergency room. Instead, she sent out a distress call. One of the paramedics rushed to her house and gave her an IV diuretic medication, which helped her urinate to get rid of the excess fluid.

A small number of the estimated 300 people who have gone through the program had to be admitted to the hospital, Dr. Busigin said. Nationally, he said, about 5%-10% are admitted. But readmissions among the patients in the Covenant program have been 25% lower than for patients who received conventional hospital care and had the same conditions as those in hospital-at-home.

Studies have shown that these programs not only reduce readmissions, but also cost less, on average, and create a better patient experience than traditional hospital care does. And, according to the JAMA survey, most consumers like the idea. Fifty-six percent of people who took the survey agreed with the statement that people recover faster at home than in the hospital. Fifty-nine percent agreed they’d feel safe being treated at home, and 49% said they’d be more comfortable if treated at home. 

The 1134 people who took the survey were also asked about their comfort level with providing various kinds of care to their loved ones during a hospital-at-home episode. The results varied with the type of task: For example, 82% of the respondents agreed or strongly agreed they could manage a patient’s medications, while just 41% said they’d be willing to change a feeding tube. Smaller percentages were willing to change an IV bag or a catheter or do wound care.

However, hospital-at-home programs don’t allow caregivers to take part in clinical care, which is prohibited by Medicare waivers and state licensing regulations. None of the 22 health systems that use the hospital-at-home services of Medically Home, including Covenant, ask caregivers to do anything along this line, said Pippa Shulman, DO, medical director of the company, which provides equipment, technology, and protocols for hospital programs

The only exception at Covenant, Dr. Busigin said, is that the hospital may train family members to do wound care when a patient is discharged from the hospital to Advanced Care at Home. They may also prepare meals for their loved ones, although the program provides balanced meals to patients if they want them. Ms. Stohler had some of these meals, which just had to be heated up, for the first few days of hospital-at-home, and later her relatives brought meals to her house.
 

Challenges for the Future

The number of Medicare hospital-at-home waivers has nearly doubled since 2021. A year earlier, when Medicare began reimbursing hospitals for acute care at home to help them cope with the overflow of COVID patients, there were only about 15-20 programs in the United States, said Dr. Leff of Johns Hopkins.

A big reason for the lack of use before the pandemic, Dr. Leff said, is that there was no payment system for hospitals that offered hospital-at-home. Now, they can get paid by Medicare and 10 state Medicaid programs, and a number of private payers are also coming on board. Ms. Stohler’s private insurer covered her hospital-at-home stay, and Dr. Busigin said several plans that contract with Covenant will pay for it.

Dr. Leff said he’s cautiously optimistic Congress will extend the Medicare waiver program, which is scheduled to end in December, for another 5 years. A couple of key House committees have signed off on a bill to do that, he said, and a Congressional Budget Office report found that the program did not cost Medicare more money. 

But even if the waiver is renewed, some health systems may find it tough to deliver the service. The current version of this model depends a lot on technology, because telemedicine is used and reliable communication is needed for patients in hospital-at-home. That’s why many of the hospitals hire outside vendors like Medically Home to provide the infrastructure they need.

Medically Home manages the tablets given to patients and all connection and networking services, including internet and cellphone connections. It also provides technical services in the command centers that hospitals set up for the doctors and nurses who provide care remotely. 

And the firm figures out how to deliver the standard care for each condition in each hospital-at-home. “We need to make sure that the patient is going to get what they need in the time frame it needs to be delivered in, and that it’s safe and effective for the patient,” Dr. Shulman said. “So we’ve developed logistical protocols for a multitude of disease states that allow us to provide high-acuity care in the home to a variety of complex patients.”

The health care workers use the hospital electronic health record for hospital-at-home patients, and vital signs uploaded from patient tablets flow directly into the electronic health record, she said.
 

Rural Areas Need Help

The use of hospital-at-home in rural areas holds a lot of promise, Dr. Leff said. 

“A lot of rural hospitals have been closing, and hospital-at-home could be a mechanism to create hospital-level care where facilities have closed down. It’s easier to do this in urban areas, but it can be done in rural environments as well.”

Rami Karjian, CEO of Medically Home, agreed. The firm services hospital-at-home programs in rural areas of Oklahoma and California, using cellphones and paramedics in areas that lack broadband connections and nurses, he pointed out. 

“Hospital-at-home can’t just be available to people who live in big cities,” he said. “The access problems in health care are pervasive, and this is part of how we solve access problems in rural areas.”
 

A version of this article first appeared on WebMD.com.

Jordan Stohler, a 42-year-old nurse in Knoxville, Tennessee, was readmitted to Fort Sanders Medical Center in June 2023 with sepsis after a double mastectomy. 

She spent 5 days in the hospital after surgery to clear up the infection. Then she was offered a choice: She could either stay in the hospital while she received IV antibiotics, or she could go home and have the antibiotics given to her there under the Advanced Care at Home program of Covenant Health, the nine-hospital system to which Fort Sanders belongs.

She opted to go home, where she knew she’d be more comfortable and would be close to her beloved dog. In the end, she was very glad she did. 

“I received great care in the hospital, but to be allowed to be in the comfort of your own home, to be around my dog, who I think is therapeutic, to be able to cook my own meals, and to have the same one-on-one nursing care that I would have gotten in the hospital was great,” Ms. Stohler said. “

Being cared for at home helped her heal, she said. “I probably would have gotten a little stir crazy if I’d stayed in the hospital any longer. I received excellent care at home.”

Covenant’s Advanced Care at Home program is an example of the hospital-at-home trend that has been growing rapidly since Medicare began reimbursing hospitals for this approach during the COVID pandemic. Currently, 322 hospitals in 37 states have Medicare waivers for these kinds of programs, although not all of them are currently functioning.

A recent survey published in JAMA found that nearly half of consumers would accept hospital-at-home, and more than a third were neutral on it. Only 17% said they’d rather be cared for in a brick-and-mortar hospital. 

The findings of the JAMA survey confirm those of earlier studies, said Bruce Leff, MD, a professor at Johns Hopkins Medical School in Baltimore, who has researched hospital-at-home since the 1990s. Like the new study, those trials found that the results had no relationship to individual traits, such as socioeconomic status, medical conditions, age, gender, or race. 

Whether a person felt comfortable with the idea of hospital-at-home boiled down “to a preference for receiving care at home or in the hospital,” he said. Some people distrust hospitals, and others feel insecure about receiving care at home, even if it is provided by qualified health care professionals.
 

How Patients Are Selected 

While the details of hospital-at-home vary from program to program, the basic scenario is that patients who need certain kinds of acute care can be sent home from hospitals, emergency departments, or clinics to receive that care at home. Among the kinds of conditions that make stable patients eligible are heart failure, COPD, pneumonia, cellulitis, and COVID-19, said John Busigin, MD, a hospitalist and medical director of Covenant Advanced Care at Home. 

When a patient is admitted to hospital-at-home, the hospital will send along whatever equipment and medications that person needs. In some cases, this may include a hospital bed, although Ms. Stohler used her own. An IV line was put into her arm, and the IV stand was placed next to the bed. 

Ms. Stohler received a computer tablet that she used to communicate with doctors and nurses in Covenant’s “command center” in Knoxville. She also wore a watch with a button she could push in case of an emergency. And she had a telephone line that went directly to her medical team, in case she had an issue and the tablet didn’t work.

Twice a day, or as needed, specially trained paramedics came to Ms. Stohler’s home. They checked on the IV line, changed the IV bag, performed tests, and uploaded vital signs from monitoring equipment to Ms. Stohler’s tablet so it could be transmitted to the command center. A physician assistant came in on the second and fourth days of her weeklong stay in the program, and she saw a hospitalist remotely every day.

While some hospital-at-home programs have registered nurses visit patients at home, RNs are in short supply. To fill this gap, Covenant’s program uses community paramedics who have been in the field for at least 5 years, doing everything from intubating patients and placing them on ventilators to providing advanced cardiac life support, Dr. Busigin said. To get certified as community paramedics, they go through a 3-month training program.

Shortly after Ms. Stohler went into hospital-at-home, she had another crisis. Excess fluid had built up in her body because of all the IV fluids she’d received in the hospital while fighting the sepsis. As a result, she became short of breath. If she had been discharged to home rather than hospital-at-home, she said, she would have had to go to the emergency room. Instead, she sent out a distress call. One of the paramedics rushed to her house and gave her an IV diuretic medication, which helped her urinate to get rid of the excess fluid.

A small number of the estimated 300 people who have gone through the program had to be admitted to the hospital, Dr. Busigin said. Nationally, he said, about 5%-10% are admitted. But readmissions among the patients in the Covenant program have been 25% lower than for patients who received conventional hospital care and had the same conditions as those in hospital-at-home.

Studies have shown that these programs not only reduce readmissions, but also cost less, on average, and create a better patient experience than traditional hospital care does. And, according to the JAMA survey, most consumers like the idea. Fifty-six percent of people who took the survey agreed with the statement that people recover faster at home than in the hospital. Fifty-nine percent agreed they’d feel safe being treated at home, and 49% said they’d be more comfortable if treated at home. 

The 1134 people who took the survey were also asked about their comfort level with providing various kinds of care to their loved ones during a hospital-at-home episode. The results varied with the type of task: For example, 82% of the respondents agreed or strongly agreed they could manage a patient’s medications, while just 41% said they’d be willing to change a feeding tube. Smaller percentages were willing to change an IV bag or a catheter or do wound care.

However, hospital-at-home programs don’t allow caregivers to take part in clinical care, which is prohibited by Medicare waivers and state licensing regulations. None of the 22 health systems that use the hospital-at-home services of Medically Home, including Covenant, ask caregivers to do anything along this line, said Pippa Shulman, DO, medical director of the company, which provides equipment, technology, and protocols for hospital programs

The only exception at Covenant, Dr. Busigin said, is that the hospital may train family members to do wound care when a patient is discharged from the hospital to Advanced Care at Home. They may also prepare meals for their loved ones, although the program provides balanced meals to patients if they want them. Ms. Stohler had some of these meals, which just had to be heated up, for the first few days of hospital-at-home, and later her relatives brought meals to her house.
 

Challenges for the Future

The number of Medicare hospital-at-home waivers has nearly doubled since 2021. A year earlier, when Medicare began reimbursing hospitals for acute care at home to help them cope with the overflow of COVID patients, there were only about 15-20 programs in the United States, said Dr. Leff of Johns Hopkins.

A big reason for the lack of use before the pandemic, Dr. Leff said, is that there was no payment system for hospitals that offered hospital-at-home. Now, they can get paid by Medicare and 10 state Medicaid programs, and a number of private payers are also coming on board. Ms. Stohler’s private insurer covered her hospital-at-home stay, and Dr. Busigin said several plans that contract with Covenant will pay for it.

Dr. Leff said he’s cautiously optimistic Congress will extend the Medicare waiver program, which is scheduled to end in December, for another 5 years. A couple of key House committees have signed off on a bill to do that, he said, and a Congressional Budget Office report found that the program did not cost Medicare more money. 

But even if the waiver is renewed, some health systems may find it tough to deliver the service. The current version of this model depends a lot on technology, because telemedicine is used and reliable communication is needed for patients in hospital-at-home. That’s why many of the hospitals hire outside vendors like Medically Home to provide the infrastructure they need.

Medically Home manages the tablets given to patients and all connection and networking services, including internet and cellphone connections. It also provides technical services in the command centers that hospitals set up for the doctors and nurses who provide care remotely. 

And the firm figures out how to deliver the standard care for each condition in each hospital-at-home. “We need to make sure that the patient is going to get what they need in the time frame it needs to be delivered in, and that it’s safe and effective for the patient,” Dr. Shulman said. “So we’ve developed logistical protocols for a multitude of disease states that allow us to provide high-acuity care in the home to a variety of complex patients.”

The health care workers use the hospital electronic health record for hospital-at-home patients, and vital signs uploaded from patient tablets flow directly into the electronic health record, she said.
 

Rural Areas Need Help

The use of hospital-at-home in rural areas holds a lot of promise, Dr. Leff said. 

“A lot of rural hospitals have been closing, and hospital-at-home could be a mechanism to create hospital-level care where facilities have closed down. It’s easier to do this in urban areas, but it can be done in rural environments as well.”

Rami Karjian, CEO of Medically Home, agreed. The firm services hospital-at-home programs in rural areas of Oklahoma and California, using cellphones and paramedics in areas that lack broadband connections and nurses, he pointed out. 

“Hospital-at-home can’t just be available to people who live in big cities,” he said. “The access problems in health care are pervasive, and this is part of how we solve access problems in rural areas.”
 

A version of this article first appeared on WebMD.com.

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

A version of this article first appeared on Medscape.com.

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

A version of this article first appeared on Medscape.com.

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

A version of this article first appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

A version of this article first appeared on Medscape.com.

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

A version of this article first appeared on Medscape.com.

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

A version of this article first appeared on Medscape.com.

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.