Individuals with HIV have a significantly higher risk of cardiovascular disease (CVD), but clinicians haven’t always understood this connection. In a new scientific statement, the American Heart Association (AHA) offers some causal explanations for the HIV/CVD relationship and proposes a pragmatic approach to assessing risk for and preventing atherosclerotic CVD (ASCVD) in patients with treated HIV infection.

The global burden of HIV-associated CVD has tripled over the last 20 years, accounting for 2.6 million disability-adjusted life-years annually, according to the statement. Compared with uninfected individuals, the risk of developing CVD-related ailments for people living with HIV is 1.5 to 2 times more likely. Some clinical factors such as smoking and viral load are more relevant for assessing risk than other variables such as triglycerides or certain biomarkers.

The statement outlines a risk assessment algorithm for adults who have treated, virally suppressed HIV based on whether they have clinical ASCVD, low-density lipoprotein cholesterol levels ≥190 mg/dL, are between the ages of 45-75, and have diabetes. Individuals at low risk for these factors would then undergo an ASCVD risk assessment using the American College of Cardiology/AHA ASCVD risk estimation tool or other similar methods. The algorithm also considers whether a patient has HIV-related risk-enhancing factors such as a CD4 count <350 cells/mm.

HIV-related factors such as advanced immunosuppression and detectable HIV viral load appear to contribute to CVD risk, Matthew J. Feinstein, MD, MSc, chair of the writing group for the statement, and an assistant professor of medicine, cardiology, and preventive medicine at the Northwestern University Feinberg School of Medicine in Chicago, told CLN Stat. “Chronic inflammation and immune activation, even when HIV is under good control, can cause buildup of plaque in the body’s arteries (including in the heart) and also may cause dysfunction of the heart muscle,” resulting in heart attack, heart failure, and stroke, he explained.

The AHA statement cited as additional contributors other common heart disease risk factors such as smoking and hypertension.

All of these factors underscore how important it is for individuals living with HIV to continue taking their antiretroviral (ART) therapies regularly, Feinstein emphasized. Some have questioned the impact of certain HIV medications on heart disease risk, particularly their effects on blood cholesterol. However, the common thought now is they are not a primary driver of risk, considering that ART therapies have become less toxic over time. These drugs are essential to treating HIV and reducing non-AIDS events like CVD, Feinstein said.

With the exception of simvastatin and lovastatin, “stains appear to be generally safe in HIV although more data are needed to fully understand the risks and benefits of these and other CVD-preventive therapies in HIV,” he added. “What is clear is that treating HIV with medications is far superior from an overall health as well as heart health standpoint compared with not treating HIV.”

Deviating from 2018 guidelines AHA issued jointly with the American College of Cardiology, the writing group did not count triglycerides as a significant risk enhancer for atherosclerotic cardiovascular disease (ASCVD). “Studies in large HIV cohorts demonstrated that triglyceride levels, which are often labile and sensitive to ART changes in HIV, either were not predictive of CVD end points independently of other traditional CVD risk factors or were associated with marginally elevated ASCVD risk,” the authors explained.

Feinstein clarified that the risk calculators in the statement (such as the ACC/AHA ASCVD risk estimator) actually do incorporate triglycerides into the risk assessment/score, “albeit somewhat indirectly.” As he explained, “triglycerides are strongly associated with total cholesterol, as they are a major part of the total cholesterol calculation, and inversely associated with high-density lipoprotein (HDL) cholesterol. Both total cholesterol and HDL cholesterol are factored into the ASCVD risk assessment.”

Although their approaches to triglycerides differ, the two AHA statements address different populations, Feinstein noted. The 2018 guidelines jointly issued with ACC were for the general population and not HIV-specific. The 2019 statement is the first to address HIV.

The writing group also decided not to recommend routine measurement of subclinical atherosclerosis via imaging or inflammatory biomarkers. “The reason we don’t outright recommend doing this for particular groups of patients is we don’t have enough data for people with HIV to support routine use of these measurements,” Feinstein explained. Such measurements are most appropriate at intermediate risk levels (7.5% to 20% 10-year ASCVD risk in the general population and probably lower predicted ASCVD risk levels in HIV, given higher unmeasured risk factors), “when a positive or negative may significantly reclassify someone’s predicted risk for ASCVD and therefore change the apparent risk/benefit of starting lipid-lowering therapy, for instance,” according to Feinstein.

In its statement, the working group mentions that findings of subclinical atherosclerosis via imaging or elevated levels of certain biomarkers (such as C-reactive protein) may be used to reclassify risk, leading someone to be considered higher risk and therefore more likely to benefit from lipid-lowering therapy. Bottom line: The measurement of these markers is essentially up to individual patients and clinicians, with the understanding that intermediate risk levels “are where we tend to learn the most in terms of risk reclassification from these complementary studies,” Feinstein summarized.