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HIV and Cardiovascular Disease

June 2015

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Predicting CVD Risk in HIV Positive People

To further investigate the issue of CVD risk prediction in HIV, investigators in Boston calculated the Framingham risk scores and ACC/AHA risk scores in the Partner's Cohort (n=2270 patients) in a 3 year interval ending in 2009.9 Risk scores were discordant in 17% of individuals with the ACC/AHA risk calculator predicting risk in 10% of patients and FRS predicting high risk in 7% of individuals. Both the ACC/AHA risk score and the FRS underestimated CVD risk in HIV patients, comparing 5-year observed to predicted event rates.

Four different risk calculators were compared in the HIV Outpatient Study which represents 2,392 individuals receiving care at 10 US clinic sites as of September 2013 and had a year of follow up, one assessment of cholesterol and two measurements of blood pressure.10

The Framingham point score, pooled cohort equation, systematic coronary risk evaluation and DAD equations were compared as shown in Table 2.

Table 2. Comparison of Four Risk Calculators in HIV Positive People
HOPS Participants (n=2,392) 10 Years CVD Risk Estimation
Framingham point score (FPS) Pooled cohort equations (PCE) Systemeic coronary risk evaluation (SCORE) D:A:D equation
Harrell's C-statistic * 0.71 0.71 0.57 0.72
Expected events (E) 126 147 19 193
Observed events (O) 149 178 19 256
Ration E/O 0.85 0.83 0.83 0.75
p-value 0.002   0.02  

* Harrell's C-statistic assessed the ability of each prediction model to discriminate patients who did or did not experience incident CVD events.

Overall all four risk prediction equations underestimated the 10 year risk of CVD in this HOPS cohort of HIV positive adults in the U.S. The FPS, PCE, and D:A:D equations had moderate discrimination with a c-statistic ranging from 0.68 to 0.72 and SCORE had poor discrimination (c-statistic = 0.57).

The Veterans Aging Cohort Study Virtual Cohort (VACS VC) was used to evaluate the role of copy years of viraemia, CD4 years, and VACS index years (age, HIV-1 RNA, CD4, LFTs, Hg, platelet, creatinine, and known HCV infection).11


Among 12,131 individuals included in the analysis, three cumulative measures provided added information about risk of acute myocardial infarction: HIV viral load copy years (VCY), CD4 count years (CD4Y), and the VACS index years (VISI).

While all three cumulative measures predicted the studied outcome, VCY ≥63,000 copy years/mL (HR=4.17; 95%CI=3.59-4.85) and CD4Y3 (HR=5.61; 95%CI=4.56-6.90); patients with higher VACS Index score-years had the highest risk of AMI (VISY ≥250; HR=40.56; 95%CI=33.25-49.47).

The authors concluded that participants with the highest cumulative viraemia (in the upper quartile of viraemia copy-years) ran a 2.6-fold increased risk of MIs. Cumulative CD4 counts were not statistically significantly associated with an increase of MI incidence.

Participants in the highest quartile of VACS index score years ran a 4 times higher risk of MI incidence during the study.

These results showing that risk predictor algorithms developed in non-HIV populations do not apply to HIV infected individuals is not surprising. They do not take into account HIV-related features that likely contribute including ART, chronic inflammation, and immune activation. Interestingly, even the D:A:D calculator which was developed in HIV performed similarly to the other calculators demonstrating that even in HIV, one size does not fit all -- suggesting perhaps differences in the HOPS patient populations as compared to the DAD individuals. Validation of HIV-specific risk calculators in different HIV cohorts will be needed in the future.

Further Support for Abacavir Link to MI

Two studies from NA-ACCORD were also featured. Frank Palella and colleagues looked at recent abacavir use and incident MIs using MESA criteria in the North American Cohort (NA-ACCORD).12

There were a total of 301 incident MIs in 16,733 adults and 64,607 person-years of follow up. Recent abacavir use (defined as prescription within 6 months) was associated with an increased risk of MI (aHR 1.71; 95%CI 1.11 to 2.64) in an adjusted models that were analogous to ones used in DAD, and the results linking current abacavir use to MI risk is similar to the original DAD result reported in 2009. In the full study population in the adjusted analysis, the significance was lost. However, in the restricted population, the finding remained significant even after adjustment. Of note, this is the first study to show risk of ABC present among ART naive individuals initiating ART, which is a new contribution to the field. The controversy over abacavir seems to ebb and tide but has not gone away.

Daniel Drozd and colleagues from NA-ACCORD determined the incidence of adjudicated primary MIs distinct from secondary MIs and examined baseline risk factors for primary MIs. The Universal Definition of MI, includes primary (type 1) MIs due to atherothrombotic plaque, and secondary (type 2) MIs due to a mismatch in supply/demand -- for example, troponin leak in the setting of sepsis. Seven NA-ACCORD cohorts were included in the study between 1996-2010, resulting in 24,919 individuals with 262 type 1 MIs and 205 type 2 MIs. Traditional risk factors, along with lower CD4 counts were associated with type 1 MIs. In contrast, sepsis, cocaine, respiratory failure, and hypertensive emergency were responsible for 50% of type 2 MIs.

This study is an important contribution as it is the first to acknowledge the differences in MI definitions which impact treatment and conclusions drawn from studies. For example, type 2 MIs are not usually treated with aspirin, beta blockers, statins etc but typically by addressing the primary issue -- i.e. drug use, sepsis which is in contrast to type 1 MIs. The distinction between type 1 and type 2 MIs in HIV cohorts thus is a critical one and may underlie some of the contrasting data that has been previously reported in different cohort studies.

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This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.

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