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ORLANDO – , according to a “big data” registry study from the United Kingdom.
“Our data show infection was just as much a risk factor or more compared with the traditional atherosclerotic cardiovascular disease risk factors,” Paul Carter, MD, said at the annual meeting of the American College of Cardiology.
Dr. Carter of Aston Medical School in Birmingham, England, presented a retrospective analysis from the ACALM (Algorithm for Comorbidities Associated with Length of stay and Mortality) study of administrative data on all of the more than 1.22 million patients admitted to seven U.K. hospitals in 2000-2013. His analysis included all 34,027 adults aged 40 years or older admitted with a urinary tract or respiratory infection on their index hospitalization who had no history of ischemic heart disease or ischemic stroke.
These patients, with a mean age of 73 years, 59% of whom were women, were compared with an equal number of age- and gender-matched adults whose index hospitalization was for reasons other than ischemic heart disease, stroke, urinary tract infection (UTI), or respiratory infection – the two most common infections resulting in hospitalization in the United Kingdom.
Patients with a respiratory infection or UTI had a 9.9% incidence of new-onset ischemic heart disease and a 4.1% rate of ischemic stroke during follow-up starting upon discharge from their index hospitalization, significantly higher than the 5.9% and 1.5% rates in controls. In a multivariate logistic regression analysis adjusted for demographics, standard cardiovascular risk factors, and the top 10 causes of mortality in the United Kingdom, patients with respiratory infection or UTI as their admitting diagnosis had a 1.36-fold increased likelihood of developing ischemic heart disease post discharge and a 2.5-fold greater risk of ischemic stroke than matched controls.
Moreover, mortality following diagnosis of ischemic heart disease was 75.2% in patients whose index hospitalization was for infection, compared with 51.1% in controls who developed ischemic heart disease without a history of hospitalization for infection, for an adjusted 2.98-fold increased likelihood of death. Similarly, mortality after an ischemic stroke was 59.8% in patients with a prior severe infection, compared with 30.8% in controls, which translated to an adjusted 3.1-fold increased risk of death post stroke in patients with a prior hospitalization for infection.
In the multivariate analysis, hospitalization for infection was a stronger risk factor for subsequent ischemic stroke than was atrial fibrillation, heart failure, type 1 or type 2 diabetes, hypertension, or hyperlipidemia. The risk of ischemic heart disease in patients with an infectious disease hospitalization was similar to the risks associated with most of those recognized risk factors.
Two possible mechanisms by which infection might predispose to subsequent ischemic heart disease and stroke are via a direct effect whereby pathogens such as Chlamydia pneumoniae are taken up into arterial plaques, where they cause a local inflammatory response, or an indirect effect in which systemic inflammation primes the atherosclerotic plaque through distribution of inflammatory cytokines, according to Dr. Carter.
He said the ACALM findings are particularly intriguing when considered in the context of the 2017 results of the landmark CANTOS trial, in which canakinumab (Ilaris), a targeted anti-inflammatory agent that inhibits the interleukin-1 beta innate immunity pathway, reduced recurrent ischemic events in post-MI patients who had high systemic inflammation as evidenced by their elevated C-reactive protein level but a normal-range LDL cholesterol (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
“If atherosclerosis is an inflammatory condition, this begs the question of whether other inflammatory conditions, like infection, which induces a large systemic inflammatory response, might drive atherosclerosis,” Dr. Carter commented.
“It’s now very well understood that inflammatory mediators, cells, and processes are involved in every step from the initial endothelial dysfunction that leads to uptake of LDL, inflammatory cells, and monocytes all the way through to plaque progression and rupture, where Th1 cytokines have been implicated in causing that rupture, and ultimately in patient presentation at the hospital,” he added.
He sees the ACALM findings as hypothesis generating, serving to help lay the groundwork for future clinical trials of vaccine or anti-inflammatory antibiotic therapies.
Dr. Carter reported having no financial conflicts related to his presentation.
SOURCE: Carter P. ACC 2018, Abstract 1325M-0.
ORLANDO – , according to a “big data” registry study from the United Kingdom.
“Our data show infection was just as much a risk factor or more compared with the traditional atherosclerotic cardiovascular disease risk factors,” Paul Carter, MD, said at the annual meeting of the American College of Cardiology.
Dr. Carter of Aston Medical School in Birmingham, England, presented a retrospective analysis from the ACALM (Algorithm for Comorbidities Associated with Length of stay and Mortality) study of administrative data on all of the more than 1.22 million patients admitted to seven U.K. hospitals in 2000-2013. His analysis included all 34,027 adults aged 40 years or older admitted with a urinary tract or respiratory infection on their index hospitalization who had no history of ischemic heart disease or ischemic stroke.
These patients, with a mean age of 73 years, 59% of whom were women, were compared with an equal number of age- and gender-matched adults whose index hospitalization was for reasons other than ischemic heart disease, stroke, urinary tract infection (UTI), or respiratory infection – the two most common infections resulting in hospitalization in the United Kingdom.
Patients with a respiratory infection or UTI had a 9.9% incidence of new-onset ischemic heart disease and a 4.1% rate of ischemic stroke during follow-up starting upon discharge from their index hospitalization, significantly higher than the 5.9% and 1.5% rates in controls. In a multivariate logistic regression analysis adjusted for demographics, standard cardiovascular risk factors, and the top 10 causes of mortality in the United Kingdom, patients with respiratory infection or UTI as their admitting diagnosis had a 1.36-fold increased likelihood of developing ischemic heart disease post discharge and a 2.5-fold greater risk of ischemic stroke than matched controls.
Moreover, mortality following diagnosis of ischemic heart disease was 75.2% in patients whose index hospitalization was for infection, compared with 51.1% in controls who developed ischemic heart disease without a history of hospitalization for infection, for an adjusted 2.98-fold increased likelihood of death. Similarly, mortality after an ischemic stroke was 59.8% in patients with a prior severe infection, compared with 30.8% in controls, which translated to an adjusted 3.1-fold increased risk of death post stroke in patients with a prior hospitalization for infection.
In the multivariate analysis, hospitalization for infection was a stronger risk factor for subsequent ischemic stroke than was atrial fibrillation, heart failure, type 1 or type 2 diabetes, hypertension, or hyperlipidemia. The risk of ischemic heart disease in patients with an infectious disease hospitalization was similar to the risks associated with most of those recognized risk factors.
Two possible mechanisms by which infection might predispose to subsequent ischemic heart disease and stroke are via a direct effect whereby pathogens such as Chlamydia pneumoniae are taken up into arterial plaques, where they cause a local inflammatory response, or an indirect effect in which systemic inflammation primes the atherosclerotic plaque through distribution of inflammatory cytokines, according to Dr. Carter.
He said the ACALM findings are particularly intriguing when considered in the context of the 2017 results of the landmark CANTOS trial, in which canakinumab (Ilaris), a targeted anti-inflammatory agent that inhibits the interleukin-1 beta innate immunity pathway, reduced recurrent ischemic events in post-MI patients who had high systemic inflammation as evidenced by their elevated C-reactive protein level but a normal-range LDL cholesterol (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
“If atherosclerosis is an inflammatory condition, this begs the question of whether other inflammatory conditions, like infection, which induces a large systemic inflammatory response, might drive atherosclerosis,” Dr. Carter commented.
“It’s now very well understood that inflammatory mediators, cells, and processes are involved in every step from the initial endothelial dysfunction that leads to uptake of LDL, inflammatory cells, and monocytes all the way through to plaque progression and rupture, where Th1 cytokines have been implicated in causing that rupture, and ultimately in patient presentation at the hospital,” he added.
He sees the ACALM findings as hypothesis generating, serving to help lay the groundwork for future clinical trials of vaccine or anti-inflammatory antibiotic therapies.
Dr. Carter reported having no financial conflicts related to his presentation.
SOURCE: Carter P. ACC 2018, Abstract 1325M-0.
ORLANDO – , according to a “big data” registry study from the United Kingdom.
“Our data show infection was just as much a risk factor or more compared with the traditional atherosclerotic cardiovascular disease risk factors,” Paul Carter, MD, said at the annual meeting of the American College of Cardiology.
Dr. Carter of Aston Medical School in Birmingham, England, presented a retrospective analysis from the ACALM (Algorithm for Comorbidities Associated with Length of stay and Mortality) study of administrative data on all of the more than 1.22 million patients admitted to seven U.K. hospitals in 2000-2013. His analysis included all 34,027 adults aged 40 years or older admitted with a urinary tract or respiratory infection on their index hospitalization who had no history of ischemic heart disease or ischemic stroke.
These patients, with a mean age of 73 years, 59% of whom were women, were compared with an equal number of age- and gender-matched adults whose index hospitalization was for reasons other than ischemic heart disease, stroke, urinary tract infection (UTI), or respiratory infection – the two most common infections resulting in hospitalization in the United Kingdom.
Patients with a respiratory infection or UTI had a 9.9% incidence of new-onset ischemic heart disease and a 4.1% rate of ischemic stroke during follow-up starting upon discharge from their index hospitalization, significantly higher than the 5.9% and 1.5% rates in controls. In a multivariate logistic regression analysis adjusted for demographics, standard cardiovascular risk factors, and the top 10 causes of mortality in the United Kingdom, patients with respiratory infection or UTI as their admitting diagnosis had a 1.36-fold increased likelihood of developing ischemic heart disease post discharge and a 2.5-fold greater risk of ischemic stroke than matched controls.
Moreover, mortality following diagnosis of ischemic heart disease was 75.2% in patients whose index hospitalization was for infection, compared with 51.1% in controls who developed ischemic heart disease without a history of hospitalization for infection, for an adjusted 2.98-fold increased likelihood of death. Similarly, mortality after an ischemic stroke was 59.8% in patients with a prior severe infection, compared with 30.8% in controls, which translated to an adjusted 3.1-fold increased risk of death post stroke in patients with a prior hospitalization for infection.
In the multivariate analysis, hospitalization for infection was a stronger risk factor for subsequent ischemic stroke than was atrial fibrillation, heart failure, type 1 or type 2 diabetes, hypertension, or hyperlipidemia. The risk of ischemic heart disease in patients with an infectious disease hospitalization was similar to the risks associated with most of those recognized risk factors.
Two possible mechanisms by which infection might predispose to subsequent ischemic heart disease and stroke are via a direct effect whereby pathogens such as Chlamydia pneumoniae are taken up into arterial plaques, where they cause a local inflammatory response, or an indirect effect in which systemic inflammation primes the atherosclerotic plaque through distribution of inflammatory cytokines, according to Dr. Carter.
He said the ACALM findings are particularly intriguing when considered in the context of the 2017 results of the landmark CANTOS trial, in which canakinumab (Ilaris), a targeted anti-inflammatory agent that inhibits the interleukin-1 beta innate immunity pathway, reduced recurrent ischemic events in post-MI patients who had high systemic inflammation as evidenced by their elevated C-reactive protein level but a normal-range LDL cholesterol (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
“If atherosclerosis is an inflammatory condition, this begs the question of whether other inflammatory conditions, like infection, which induces a large systemic inflammatory response, might drive atherosclerosis,” Dr. Carter commented.
“It’s now very well understood that inflammatory mediators, cells, and processes are involved in every step from the initial endothelial dysfunction that leads to uptake of LDL, inflammatory cells, and monocytes all the way through to plaque progression and rupture, where Th1 cytokines have been implicated in causing that rupture, and ultimately in patient presentation at the hospital,” he added.
He sees the ACALM findings as hypothesis generating, serving to help lay the groundwork for future clinical trials of vaccine or anti-inflammatory antibiotic therapies.
Dr. Carter reported having no financial conflicts related to his presentation.
SOURCE: Carter P. ACC 2018, Abstract 1325M-0.
REPORTING FROM ACC 2018
Key clinical point: Once patients have been hospitalized for a respiratory infection or UTI, their postdischarge risk of ischemic stroke is 2.5-fold greater than in those without such a history.
Major finding: Patients with a history of hospitalization for UTI or a respiratory infection who later develop ischemic heart disease or stroke have a threefold higher mortality risk than those without such a hospitalization.
Study details: This was a retrospective study of more than 68,000 subjects in the U.K. ACALM registry study.
Disclosures: The study presenter reported having no financial conflicts of interest.
Source: Carter P. ACC 2018, Abstract 1325M-0.