Correlation of Inflammatory Biomarkers with the Framingham Coronary Risk Score in Antiretroviral-naïve HIV-1 Infected Patients
Reported by Jules Levin
17th CROI Feb 16-19 2010 SF
Parul Patel1, Henry Zhao1, Lisa G Patel1, Amanda Peppercorn1, Paul Wannamaker1, Martin J Gartland2, and Mark Shaefer 2
1GlaxoSmithKline, Research Triangle Park, NC, USA; 2ViiV Healthcare, Research Triangle Park, NC, USA
HIV-infected patients appear to have higher rates of CVD (e.g. myocardial infarctions) than uninfected individuals that might be impacted by host factors
(ie; increased smoking rates), chronic viral infection, and metabolic changes.
FRS and all 3 biomarkers appeared to correlate in this virologically suppressed,
However, elevations in hs-CRP were non-specific and denoted average CV risk
even for subjects with FRS ≥ 10%.
Similarly, statistically significant elevations in IL-6 and Lp-PLA2 were also observed, however, the magnitude of the change was small between groups and are difficult to interpret or apply to clinical practice.
Framingham coronary risk scores and biomarker concentrations correlated well in this ART-naïve, virologically suppressed ARIES study population.
The clinical utility of assessing inflammatory biomarkers for CV risk beyond FRS requires further study.
Background: The presence of traditional risk factors for coronary heart disease
(CHD) strongly predicts the risk of cardiovascular (CV) disease in both the general and HIV-1 infected patient populations. Although the Framingham (FRAM) equation for CV risk prediction has performed reasonably well in HIV-1 infected patients, the incremental value of measuring inflammatory biomarkers remains unclear. We evaluated the correlation between biomarker concentrations and FRAM risk scores in antiretroviral (ART)-naïve subjects.
Methods: CV risk and inflammatory biomarker concentrations were evaluated in
363/419 (87%) ART-naïve subjects enrolled in the ongoing ARIES trial comparing ritonavir-boosted atazanavir (ATV) with unboosted ATV each with
abacavir/lamivudine. High CV risk was not exclusionary to participation. FRAM risk and concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were assessed at BL and week 84. Biomarker concentrations were compared between FRAM 10-year risk groups (< or ≥ 10%).
Results: FRAM risk scores were generally low and similar between arms at BL; <5% (79%), 5-<10% (11%), 10-<20% (8%), ≥ 20% (2%). Among subjects with smoking data at BL, 77% of smokers and 97% of non-smokers had a risk score <10%. At week 84, 93% of subjects with biomarker assessments had an HIV-1 RNA <50 copies/mL. Biomarker levels by FRAM risk score are presented below.
Conclusion: In this ART-naïve population, inflammatory biomarker levels
appeared to correlate with the Framingham risk score. Subjects with a risk score
≥10% had generally higher biomarker concentrations, including hsCRP, the only
clinically validated marker of CV risk. The clinical utility of inflammatory biomarker
data to augment traditional Framingham cardiovascular risk assessment requires
further study among subjects with virologic suppression receiving contemporary
HIV-1 infected patients are at increased risk of cardiovascular disease (CVD) attributable to the host, virus, and possibly antiretroviral therapy (ART).1
The risk for coronary heart disease (CHD) is strongly associated with the presence of modifiable and non-modifiable factors based on data from the Framingham Heart Study of a largely middle-aged Caucasian population.2
In the presence of one or more risk factors, the cumulative risk is multiplicative and not simply additive
A risk tool to calculate the 10-year risk of developing hard CHD (MI and coronary death) is readily available which incorporates the following factors:
- age, gender, total cholesterol, HDL-cholesterol, smoking status, systolic
blood pressure and anti-hypertensive medication use.3
- Patients with 0-1 risk factors are assumed to have <10% risk; 2+ risk factors
have ≤ 20% risk; those with CHD or CHD risk equivalents have a 10-year
CHD risk >20%.4
Inflammation is also an emerging risk factor for CVD due to its central role in
atherosclerosis development, thus the continued interest in evaluating inflammatory biomarkers.
10-year Framingham CV risk scores were calculated at baseline (BL) from available data and correlated with inflammatory biomarker levels in 363/419 (87%) ART-naïve subjects in the ongoing ARIES trial.
The 144-week ARIES trial enrolled 419 ART-naïve subjects to participate in an induction-simplification strategy and demonstrated the virologic non-inferiority of a simplified regimen of unboosted atazanavir (ATV) + abacavir/lamivudine (ABC/3TC) compared to ATV + ritonavir (ATV/r) + ABC/3TC over 84 weeks.5
Plasma samples were prospectively analyzed for hsCRP, IL-6, and Lp-PLA2 at BL and week 84.
lipoprotein associated phospholipase A2 (Lp-PLA2) is involved in the modification of lipids within the atheroma.
High cardiovascular risk was not exclusionary to participation.
Descriptive statistics, Spearman's rank order association, and p-values were
There were no significant differences among BL characteristics between arms,
except for CDC class C disease.
22% of men were >45 years while 17% of women were >55 years of age.
Figure 1. BL Framingham Coronary Risk Scores
The majority of subjects had low cardiovascular risk at baseline.
Among subjects with smoking data (363/419), 77% of smokers and 97% of
non-smokers had 10-year risk score <10% at baseline.
At week 84, 93% of subjects with biomarker assessments had a HIV-1 RNA
Statistically significant association between all 3 biomarkers and coronary risk was observed on chronic ART with virologic suppression.
Hs-crp (only validated marker of CV risk in non-HIV infected populations) did not change appreciably between low-moderate and moderate-high risk groups
(ie; clinical cutoff for hsCRP <3 mg/dL denotes average risk).
There was no difference in biomarker concentrations or FRS by treatment arm
(data not shown).
1. Currier JS. Update on cardiovascular complications in HIV infection. Top HIV Med 2009; 17:98-103.
2. Wilson P, D'Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97:1837-1847.
3. 10-Year CHD Risk Assessment Calculator.
http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof. Accessed January 19, 2010.
4. Third report of the expert panel on the detection, evaluation, and treatment of high blood Cholesterol in adults (Adult Treatment Panel III) executive summary. http://www.nhlbi.nih.gov/guidelines/cholesterol/atip iii.htm. Accessed January 19, 2010.
5. Squires K, Young B, DeJesus E, et al. Similar efficacy and tolerability of
atazanavir (ATV) compared to ATV/ritonavir (RTV, r), each in combination with abacavir/lamivudine (ABC/3TC), after initial suppression with ABC/3TC + ATV/r in HIV-1 infected patients: 84-week results of the ARIES trial. In: Program and abstracts of the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 19-22, 2009; Cape Town, South Africa. Abstract WELBB103.