Cholesterol Guidelines Applied to HIV-infected Patients
Cholesterol Guidelines Applied to HIV-infected Patients
In November 2013, the American College of Cardiology/American Heart Association (ACC/AHA) released a Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. This guideline replaced the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III – or ATP III – guideline), last updated in 2004. Cholesterol treatment guidelines such as these, designed for the general population, are typically extrapolated to HIV-infected patients. However, among HIV-infected patients, unique factors relating to infection, treatment, and the body's immune response may contribute to cardiovascular disease (CVD) risk. In addition, studies show that HIV-infected patients have more high-risk coronary plaque that may potentially increase risk for CVD events. Nontraditional CVD risk factors and noninvasive cardiac imaging data are not included in traditional CVD risk assessment algorithms. Thus, a critical question arises as to how well current guidelines identify HIV-infected patients at highest CVD risk who would benefit most from statin therapy.
Relative to 2004 guidelines, 2013 ACC/AHA guidelines introduce major changes for identifying those for whom statins would be recommended, and the implications for HIV-infected patients remain unclear. The 2004 guidelines relied on low-density lipoprotein (LDL) cholesterol level thresholds tied to an individual's CVD risk categorization. Categorizations were, in turn, based on number of coronary heart disease (CHD) risk factors/risk equivalents and 10-year Framingham risk score (FRS) for hard CHD – that is percentage risk of myocardial infarction (MI) or coronary death in the next 10 years. The 2004 guidelines further defined non-high-density lipoprotein (non-HDL) cholesterol thresholds for drug therapy upon achievement of LDL goals. In contrast, the 2013 ACC/AHA guidelines abandoned LDL and non-HDL thresholds and goals and instead identified four groups likely to benefit from statin therapy. Benefit groups included individuals: age 21 or older with clinical atherosclerotic cardiovascular disease (ASCVD); age 21 or older with LDL 190 mg/dl or higher; age 40–75 with diabetes and LDL 70–189 mg/dl; and age 40–75 with a 10-year ASCVD risk score – that is, percentage risk of nonfatal MI, coronary death, nonfatal/fatal stroke within the next 10 years – 7.5% or higher by the Pooled Cohort Equations calculator. Analysis of data from 3773 participants in the National Health and Nutrition Examination Surveys (NHANES) database has suggested that application of 2013 ACC/AHA guidelines (versus 2004 guidelines) would markedly increase the percentage of individuals for whom statins would be recommended, but specific data in the HIV population have not been obtained.
Since the release of the 2013 ACC/AHA guidelines, use of the 10-year ASCVD risk score to determine recommendations for statin therapy has come under scrutiny. When applied to selected primary prevention cohorts, the calculator appears to overestimate observed CVD events by 75–150%. However, the 2013 ASCVD risk calculator may underestimate risk among groups of patients – including HIV-infected patients – in whom atherosclerosis is driven, in part, by nontraditional CVD risk factors. Authors of the guidelines suggest that for individuals outside designated statin benefit groups who are nevertheless considered to be at high risk for CVD, noninvasive cardiac imaging studies may provide useful additional data to consider.
Our research group and others have employed noninvasive contrast-enhanced coronary computed-tomography angiography (CCTA) to characterize prevalence and morphology of subclinical coronary atherosclerosis among HIV-infected patients without clinical CVD. We and others have previously published that HIV-infected patients have more noncalcified coronary plaque and high-risk morphology (HRM) coronary plaque than matched non-HIV controls. HRM coronary plaque may be marked by low attenuation (low density compatible with a necrotic lipid core) and/or positive remodeling (dilation of vessel at plaque site), and these features suggest vulnerability to rupture. Importantly, noncalcified and HRM coronary plaque predict CVD events in the general population. Detailed information on coronary plaque morphology may be more useful than coronary artery calcium score for predicting plaque rupture and ensuing MI – particularly if accrued calcification stabilizes individual high-risk coronary plaques, as suggested by recent studies.
In the present study, we consider how 2013 ACC/AHA guidelines would apply to a cohort of well phenotyped HIV-infected patients without known CVD who have undergone CCTA. Specifically, employing 2013 ACC/AHA versus 2004 ATP III guidelines, we compare recommendations for statin therapy among HIV-infected patients with and without subclinical HRM coronary plaque. Further, we characterize differences among HIV-infected patients for whom statins would/would not be recommended and among HIV-infected patients with and without HRM coronary plaque. Finally, we determine the relationship between 2013 10-year ASCVD risk score and HRM coronary plaque burden. We hypothesize that 2013 ACC/AHA guidelines would not recommend statins for a sizeable proportion of those HIV-infected patients with subclinical high-risk coronary plaque, despite that these patients may potentially benefit from statin therapy.
Background
In November 2013, the American College of Cardiology/American Heart Association (ACC/AHA) released a Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. This guideline replaced the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III – or ATP III – guideline), last updated in 2004. Cholesterol treatment guidelines such as these, designed for the general population, are typically extrapolated to HIV-infected patients. However, among HIV-infected patients, unique factors relating to infection, treatment, and the body's immune response may contribute to cardiovascular disease (CVD) risk. In addition, studies show that HIV-infected patients have more high-risk coronary plaque that may potentially increase risk for CVD events. Nontraditional CVD risk factors and noninvasive cardiac imaging data are not included in traditional CVD risk assessment algorithms. Thus, a critical question arises as to how well current guidelines identify HIV-infected patients at highest CVD risk who would benefit most from statin therapy.
Relative to 2004 guidelines, 2013 ACC/AHA guidelines introduce major changes for identifying those for whom statins would be recommended, and the implications for HIV-infected patients remain unclear. The 2004 guidelines relied on low-density lipoprotein (LDL) cholesterol level thresholds tied to an individual's CVD risk categorization. Categorizations were, in turn, based on number of coronary heart disease (CHD) risk factors/risk equivalents and 10-year Framingham risk score (FRS) for hard CHD – that is percentage risk of myocardial infarction (MI) or coronary death in the next 10 years. The 2004 guidelines further defined non-high-density lipoprotein (non-HDL) cholesterol thresholds for drug therapy upon achievement of LDL goals. In contrast, the 2013 ACC/AHA guidelines abandoned LDL and non-HDL thresholds and goals and instead identified four groups likely to benefit from statin therapy. Benefit groups included individuals: age 21 or older with clinical atherosclerotic cardiovascular disease (ASCVD); age 21 or older with LDL 190 mg/dl or higher; age 40–75 with diabetes and LDL 70–189 mg/dl; and age 40–75 with a 10-year ASCVD risk score – that is, percentage risk of nonfatal MI, coronary death, nonfatal/fatal stroke within the next 10 years – 7.5% or higher by the Pooled Cohort Equations calculator. Analysis of data from 3773 participants in the National Health and Nutrition Examination Surveys (NHANES) database has suggested that application of 2013 ACC/AHA guidelines (versus 2004 guidelines) would markedly increase the percentage of individuals for whom statins would be recommended, but specific data in the HIV population have not been obtained.
Since the release of the 2013 ACC/AHA guidelines, use of the 10-year ASCVD risk score to determine recommendations for statin therapy has come under scrutiny. When applied to selected primary prevention cohorts, the calculator appears to overestimate observed CVD events by 75–150%. However, the 2013 ASCVD risk calculator may underestimate risk among groups of patients – including HIV-infected patients – in whom atherosclerosis is driven, in part, by nontraditional CVD risk factors. Authors of the guidelines suggest that for individuals outside designated statin benefit groups who are nevertheless considered to be at high risk for CVD, noninvasive cardiac imaging studies may provide useful additional data to consider.
Our research group and others have employed noninvasive contrast-enhanced coronary computed-tomography angiography (CCTA) to characterize prevalence and morphology of subclinical coronary atherosclerosis among HIV-infected patients without clinical CVD. We and others have previously published that HIV-infected patients have more noncalcified coronary plaque and high-risk morphology (HRM) coronary plaque than matched non-HIV controls. HRM coronary plaque may be marked by low attenuation (low density compatible with a necrotic lipid core) and/or positive remodeling (dilation of vessel at plaque site), and these features suggest vulnerability to rupture. Importantly, noncalcified and HRM coronary plaque predict CVD events in the general population. Detailed information on coronary plaque morphology may be more useful than coronary artery calcium score for predicting plaque rupture and ensuing MI – particularly if accrued calcification stabilizes individual high-risk coronary plaques, as suggested by recent studies.
In the present study, we consider how 2013 ACC/AHA guidelines would apply to a cohort of well phenotyped HIV-infected patients without known CVD who have undergone CCTA. Specifically, employing 2013 ACC/AHA versus 2004 ATP III guidelines, we compare recommendations for statin therapy among HIV-infected patients with and without subclinical HRM coronary plaque. Further, we characterize differences among HIV-infected patients for whom statins would/would not be recommended and among HIV-infected patients with and without HRM coronary plaque. Finally, we determine the relationship between 2013 10-year ASCVD risk score and HRM coronary plaque burden. We hypothesize that 2013 ACC/AHA guidelines would not recommend statins for a sizeable proportion of those HIV-infected patients with subclinical high-risk coronary plaque, despite that these patients may potentially benefit from statin therapy.