Heart Disease in RA Has Complex Etiology

When it comes to heart disease in rheumatoid arthritis, the classic risk factors like body mass index and abnormal lipid profiles play a role, but a very different one than among the general population, according to Dr. George D. Kitas and Dr. Sherine E. Gabriel.

Moreover, systemic inflammation is likely just as important for the development of cardiovascular disease in this cohort. Therefore, “effective, even optimal control of traditional risk factors is imperative, but may be insufficient to reduce CV risk for people with RA,” the investigators wrote (Ann. Rheum. Dis. 2010 Nov. 24 [doi:10.1136/ard.2010.142133]). Rather, “tight control of systemic inflammation is likely to be required for optimal results.”

According to Dr. Kitas of the Arthritis Research U.K. Epidemiology Unit at Manchester (England) University, and Dr. Gabriel of the division of rheumatology at the Mayo Clinic, Rochester, Minn., one of the commonest and simplest risk factors for heart disease among the general population – increased body mass index – may, paradoxically, be associated with increased survival among RA patients.

They point to one study showing that even after the presence of diabetes mellitus, cardiac history, smoking, and hypertension were controlled for, lower BMI carried a threefold risk of death, compared with patients without RA (Arthritis Rheum. 2004;50:3450-7).

“RA appears to be associated with profound alterations in body composition, which are not reflected in the BMI thresholds used in the general population,” the authors wrote.

These alterations include what the authors call “rheumatoid cachexia,” characterized by low muscle mass combined with a high fat mass, which may represent “from the CV perspective, the 'worst of both worlds.'”

A similar paradoxical relationship appears to exist concerning lipids in RA. “Serum levels of total cholesterol and LDL cholesterol decline precipitously during the 3- to 5-year period before RA incidence,” they wrote, citing a study by other investigators (Ann. Rheum. Dis. 2009;68[suppl. 3]:78).

On the other hand, dyslipidemia has been documented to affect “up to half” of hospitalized RA patients (Ann. Rheum. Dis. 2010;69:683-8).

Meanwhile, the landmark JUPITER study (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) excluded RA patients, because of C-reactive protein levels in excess of the “arbitrarily chosen threshold of 2 mg/L used in that trial, as well as a significant classical CV risk factor load, unlike the participants in JUPITER, who had no other risk factors.” They reported that a trial of statins specifically in RA, enrolling 4,000 patients, is underway in the United Kingdom, but will not report results until 2016 (www.dgoh.nhs.uk/tracera

Another area where research is lacking is concerning the effects of inflammation on CV risk. The authors pointed, for example, to the theory of “accelerated atherosclerosis,” first postulated in the 1990s.

“The cell types, cytokine signaling, adhesion interactions, and tissue-damaging processes involved in the generation, progression, instability, and rupture of atheromatous plaques are reminiscent of those seen in chronic rheumatoid synovitis,” they wrote.

Moreover, “effective RA treatment appears to be associated with some, often transient, improvements in vascular function,” they added, although “there are no clear, consistent relationships between this and contemporary disease activity.”

Another theory, that “high-grade systemic inflammation in RA does not necessarily imply accelerated atherosclerosis but rather an increased propensity to plaque instability and rupture,” was confirmed in an autopsy analysis in one study (J. Rheumatol. 2007;34:937-42).

The work was funded by Arthritis Research U.K., the British Heart Foundation, the Medical Research Council, and the U.S. National Institute of Arthritis and Musculoskeletal Diseases. Dr. Kitas and Dr. Gabriel said they had no relevant financial disclosures.

When it comes to heart disease in rheumatoid arthritis, the classic risk factors like body mass index and abnormal lipid profiles play a role, but a very different one than among the general population, according to Dr. George D. Kitas and Dr. Sherine E. Gabriel.

Moreover, systemic inflammation is likely just as important for the development of cardiovascular disease in this cohort. Therefore, “effective, even optimal control of traditional risk factors is imperative, but may be insufficient to reduce CV risk for people with RA,” the investigators wrote (Ann. Rheum. Dis. 2010 Nov. 24 [doi:10.1136/ard.2010.142133]). Rather, “tight control of systemic inflammation is likely to be required for optimal results.”

According to Dr. Kitas of the Arthritis Research U.K. Epidemiology Unit at Manchester (England) University, and Dr. Gabriel of the division of rheumatology at the Mayo Clinic, Rochester, Minn., one of the commonest and simplest risk factors for heart disease among the general population – increased body mass index – may, paradoxically, be associated with increased survival among RA patients.

They point to one study showing that even after the presence of diabetes mellitus, cardiac history, smoking, and hypertension were controlled for, lower BMI carried a threefold risk of death, compared with patients without RA (Arthritis Rheum. 2004;50:3450-7).

“RA appears to be associated with profound alterations in body composition, which are not reflected in the BMI thresholds used in the general population,” the authors wrote.

These alterations include what the authors call “rheumatoid cachexia,” characterized by low muscle mass combined with a high fat mass, which may represent “from the CV perspective, the 'worst of both worlds.'”

A similar paradoxical relationship appears to exist concerning lipids in RA. “Serum levels of total cholesterol and LDL cholesterol decline precipitously during the 3- to 5-year period before RA incidence,” they wrote, citing a study by other investigators (Ann. Rheum. Dis. 2009;68[suppl. 3]:78).

On the other hand, dyslipidemia has been documented to affect “up to half” of hospitalized RA patients (Ann. Rheum. Dis. 2010;69:683-8).

Meanwhile, the landmark JUPITER study (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) excluded RA patients, because of C-reactive protein levels in excess of the “arbitrarily chosen threshold of 2 mg/L used in that trial, as well as a significant classical CV risk factor load, unlike the participants in JUPITER, who had no other risk factors.” They reported that a trial of statins specifically in RA, enrolling 4,000 patients, is underway in the United Kingdom, but will not report results until 2016 (www.dgoh.nhs.uk/tracera

Another area where research is lacking is concerning the effects of inflammation on CV risk. The authors pointed, for example, to the theory of “accelerated atherosclerosis,” first postulated in the 1990s.

“The cell types, cytokine signaling, adhesion interactions, and tissue-damaging processes involved in the generation, progression, instability, and rupture of atheromatous plaques are reminiscent of those seen in chronic rheumatoid synovitis,” they wrote.

Moreover, “effective RA treatment appears to be associated with some, often transient, improvements in vascular function,” they added, although “there are no clear, consistent relationships between this and contemporary disease activity.”

Another theory, that “high-grade systemic inflammation in RA does not necessarily imply accelerated atherosclerosis but rather an increased propensity to plaque instability and rupture,” was confirmed in an autopsy analysis in one study (J. Rheumatol. 2007;34:937-42).

The work was funded by Arthritis Research U.K., the British Heart Foundation, the Medical Research Council, and the U.S. National Institute of Arthritis and Musculoskeletal Diseases. Dr. Kitas and Dr. Gabriel said they had no relevant financial disclosures.

When it comes to heart disease in rheumatoid arthritis, the classic risk factors like body mass index and abnormal lipid profiles play a role, but a very different one than among the general population, according to Dr. George D. Kitas and Dr. Sherine E. Gabriel.

Moreover, systemic inflammation is likely just as important for the development of cardiovascular disease in this cohort. Therefore, “effective, even optimal control of traditional risk factors is imperative, but may be insufficient to reduce CV risk for people with RA,” the investigators wrote (Ann. Rheum. Dis. 2010 Nov. 24 [doi:10.1136/ard.2010.142133]). Rather, “tight control of systemic inflammation is likely to be required for optimal results.”

According to Dr. Kitas of the Arthritis Research U.K. Epidemiology Unit at Manchester (England) University, and Dr. Gabriel of the division of rheumatology at the Mayo Clinic, Rochester, Minn., one of the commonest and simplest risk factors for heart disease among the general population – increased body mass index – may, paradoxically, be associated with increased survival among RA patients.

They point to one study showing that even after the presence of diabetes mellitus, cardiac history, smoking, and hypertension were controlled for, lower BMI carried a threefold risk of death, compared with patients without RA (Arthritis Rheum. 2004;50:3450-7).

“RA appears to be associated with profound alterations in body composition, which are not reflected in the BMI thresholds used in the general population,” the authors wrote.

These alterations include what the authors call “rheumatoid cachexia,” characterized by low muscle mass combined with a high fat mass, which may represent “from the CV perspective, the 'worst of both worlds.'”

A similar paradoxical relationship appears to exist concerning lipids in RA. “Serum levels of total cholesterol and LDL cholesterol decline precipitously during the 3- to 5-year period before RA incidence,” they wrote, citing a study by other investigators (Ann. Rheum. Dis. 2009;68[suppl. 3]:78).

On the other hand, dyslipidemia has been documented to affect “up to half” of hospitalized RA patients (Ann. Rheum. Dis. 2010;69:683-8).

Meanwhile, the landmark JUPITER study (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) excluded RA patients, because of C-reactive protein levels in excess of the “arbitrarily chosen threshold of 2 mg/L used in that trial, as well as a significant classical CV risk factor load, unlike the participants in JUPITER, who had no other risk factors.” They reported that a trial of statins specifically in RA, enrolling 4,000 patients, is underway in the United Kingdom, but will not report results until 2016 (www.dgoh.nhs.uk/tracera

Another area where research is lacking is concerning the effects of inflammation on CV risk. The authors pointed, for example, to the theory of “accelerated atherosclerosis,” first postulated in the 1990s.

“The cell types, cytokine signaling, adhesion interactions, and tissue-damaging processes involved in the generation, progression, instability, and rupture of atheromatous plaques are reminiscent of those seen in chronic rheumatoid synovitis,” they wrote.

Moreover, “effective RA treatment appears to be associated with some, often transient, improvements in vascular function,” they added, although “there are no clear, consistent relationships between this and contemporary disease activity.”

Another theory, that “high-grade systemic inflammation in RA does not necessarily imply accelerated atherosclerosis but rather an increased propensity to plaque instability and rupture,” was confirmed in an autopsy analysis in one study (J. Rheumatol. 2007;34:937-42).

The work was funded by Arthritis Research U.K., the British Heart Foundation, the Medical Research Council, and the U.S. National Institute of Arthritis and Musculoskeletal Diseases. Dr. Kitas and Dr. Gabriel said they had no relevant financial disclosures.