HIV infection confers elevated risk for ASCVD, CV events
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Adults in the U.S. with HIV are still at an elevated risk for atherosclerotic CVD compared with individuals without HIV, regardless of changes in antiretroviral therapies and increased statin use.
According to research published in the Journal of the American Heart Association, during a mean follow-up of 1.6 years, researchers found that among Medicare beneficiaries, rates of ASCVD and CV events were as follows:
- ASCVD: HIV, 5.53 per 1,000 person-years; no HIV, 3.49 per 1,000 person-years;
- MI: HIV, 3.58 per 1,000 person-years; no HIV, 2.34 per 1,000 person-years;
- stroke: HIV, 1.49 per 1,000 person-years; no HIV, 0.94 per 1,000 person-years; and
- lower-extremity artery disease hospitalizations: HIV, 0.65 per 1,000 person-years; no HIV, 0.31 per 1,000 person-years.
Moreover, after multivariable adjustment, researchers observed increased HRs for patients with HIV compared with those without for ASCVD (HR = 1.29; 95% CI, 1.18-1.4), MI (HR = 1.26; 95% CI, 1.13-1.39), stroke (HR = 1.3; 95% CI, 1.11-1.52) and lower-extremity artery disease hospitalizations (HR = 1.46; 95% CI, 1.11-1.92).
“Due to the change in antiretroviral therapies and more widespread primary prevention strategies, it was unclear whether the risk of CV events remained elevated,” Robert S. Rosenson, MD, director of the cardiometabolics unit at Mount Sinai Hospital and professor of medicine at the Icahn School of Medicine at Mount Sinai, told Healio. “In this contemporary analysis, we report that persons living with HIV have higher risk of atherosclerotic CV events. Although this type of analysis precludes mechanistic insight, persons living with HIV harbor the virus in their tissues, resulting in ongoing chronic inflammation.”
Patients stratified by statin use
In other findings, the risk for stroke associated with HIV infection was greater among beneficiaries not taking statins (HR = 1.3; 95% CI, 1.07-1.58) than those receiving statin therapy (HR = 1.25; 95% CI, 0.95-1.64). In addition, risk for lower-extremity artery disease hospitalization associated with HIV infection was also greater among patients not receiving statin therapy (HR = 1.62; 95% CI, 1.13-2.32) compared with their counterparts taking statins (HR = 1.27; 95% CI, 0.83-1.94).
“The chronic inflammatory state warrants comprehensive preventive approaches that include a healthy diet, exercise, smoking cessation, control of blood pressure and diabetes and cholesterol lowering,” Rosenson said in an interview. “The effects of cholesterol lowering in persons living with HIV is the purpose of the ongoing National Institutes of Health REPRIEVE trial that is investigating the effects of pitavastatin (Livalo, Kowa) vs. placebo on major adverse cardiovascular events. Other cholesterol-lowering therapies such as PCSK9 inhibitors are being evaluated in persons living with HIV who have elevated LDL cholesterol levels on maximally tolerated statin therapy.”
Differing from previous work
Researchers frequency matched 1:4 based on age, sex and calendar year 82,426 Medicare beneficiaries with HIV to 329,704 beneficiaries without HIV (79% younger than 55 years; 84% men in both groups) to assess the risk for ASCVD events between these groups. All patients had commercial or supplemental Medicare health insurance between 2011 and 2019 and were followed up until Dec. 31, 2016.
“We conducted an analysis in a national database of commercially insured U.S. adults to evaluate the risk of ASCVD events among persons living in the United States with and without HIV,” Rosenson told Healio. “Previous studies have shown that persons living with HIV had higher risk of myocardial infarction and stroke, but these studies were performed when antiretroviral therapies with adverse metabolic effects were commonplace.”
“The higher risk of ASCVD among U.S. adults with vs. without HIV was present for those taking and not taking a statin,” the researchers wrote. “Clinicians should assess ASCVD risk for their patients with HIV and provide guideline-recommended treatment to lower this risk.” – by Scott Buzby
Disclosures: Rosenson reports he received honoraria from Kowa for nonpromotional speaking and received grants and advisory board fees from Amgen, which is the sponsor of the BEIJERNICK trial of evolocumab (Repatha). Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Chris T. Longenecker, MD
This large study of the MarketScan database suggests that people living with HIV in the modern treatment era remain at risk for ASCVD events. Prior studies, particularly one from the Kaiser Permanente system in California, suggested that the relative risk for MI for people living with HIV vs. controls declined from 2005 to 2011. In contrast, this study does not suggest a declining risk. Thus, clinicians must remain vigilant and focused on aggressive risk factor modification in this population.
Much is known about the epidemiology of ASCVD events in people living with HIV and even many of the mechanisms that lead to increased risk. Yet, relatively less is known about how to overcome unique barriers to appropriate risk factor management in this population. Why are people living with HIV still undertreated with statins and what can be done about it? What can be done to help people living with HIV achieve better BP control rates? Closing the “know-do” gap for CV prevention in HIV must be a top priority.
Implementation science to explore reasons behind disparities in care and how to overcome them should be a higher priority to improve clinical outcomes. Research on unique mechanisms of disease such as inflammation and immune activation could lead to novel therapies.
Protease inhibitors have been associated with increased risk for MI and their use is on the decline during the period of this study (2011-2016), as the authors point out. However, integrase inhibitors, which have replaced protease inhibitors in many antiretroviral therapy regimens, come with their own set of problems such as significant weight gain and potentially insulin resistance. Although integrase inhibitors appear to be safer in the short term, the long-term effects of these newer drugs on CV health is still to be determined.
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