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Heart Marker (hsCRP) Tied to Lipids and Weight in People With Tight HIV Control
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XVII International AIDS Conference
August 3-8, 2008
Mexico City
Mark Mascolini
Highly sensitive C-reactive protein (hsCRP) may offer a more reliable estimate of cardiovascular disease (CVD) risk in people with well-controlled HIV infection than standard risk markers, according to results of a 94-person analysis in the Lipoatrophy and Neuropathy Cohort (LINC) Study [1]. M. Sean Boger (Vanderbilt University, Nashville, Tennessee) and LINC colleagues traced significant correlations between hsCRP and cholesterol, triglycerides, and body mass index (BMI).
LINC investigators planned this study because many HIV heart experts suspect that traditional CVD risk calculators, such as the Framingham score [2,3], underestimate heart disease risk in people taking potent antiretrovirals. In the general population hsCRP below 1 signals low CVD risk, hsCRP from 1 to 3 suggests average risk, and hsCRP above 3 signals high risk.
The study objective was to assess relationships between hsCRP and metabolic parameters in HIV-infected patients on ART.
Because uncontrolled HIV replication boosts hsCRP, Boger and coworkers believe poorly controlled HIV infection limits the value of hsCRP as a risk predictor. So they decided to track potential links between hsCRP and other CVD variables in 94 cohort members with an undetectable HIV load while taking antiretrovirals between June 2006 and July 2007.
Boger enrolled adults infected with HIV for at least a year and taking antiretrovirals for at least 24 consecutive weeks. Everyone had a viral load under 10,000 copies within 180 days of starting treatment, and all had clinical evidence of lipoatrophy, or peripheral neuropathy, or both. No cohort member had an active opportunistic infection, lactic acidosis, a history of myocardial infarction, or active cancer or chemotherapy within 12 months.
The study population included 69 men (73%) and 25 women; 54 cohort members were white (57%). Median CD4 count stood at 515 (interquartile range [IQR] 336 to 748) and median viral load at 50 copies (IQR 50 to 9285). Sixty-three people (67%) had a viral load below 50 copies, and 51 (54%) were taking a protease inhibitor (PI)--atazanavir/ritonavir in 24%, lopinavir/ritonavir in 27%, and nelfinavir in 3%. Forty-nine people (52%) smoked, and 23 (25%) were rated heavy smokers. Thirty-two cohort members (34%) had lipoatrophy, determined subjectively on a grading scale for fat loss in the face, arms, legs, or buttocks. Only 16 people (17%) were taking lipid-lowering drugs.
Over a median of 230 days, 65 of 94 study participants (69%) had two follow-up LINC visits, 41 (44%) had three, and 19 (20%) had four. Nearly half of study participants had a high-risk hsCRP reading:
- hsCRP >3 (high risk): 47 (49%)
- hsCRP 1-3 (average risk): 24 (26%)
- hsCRP <1 (low risk): 23 (25%)
Despite this preponderance of hsCRP-determined high CVD risk, median Framingham score stood only at 3 (IQR 2 to 5), which means a 10-year risk of 6% for men and 3% for women [2,3]. The Framingham score factors in age, gender, total cholesterol, "good" high-density lipoprotein (HDL) cholesterol, smoking, diabetes, and systolic blood pressure.
In an analysis factoring in age, race, gender, smoking, fasting state at lipid measurement, CD4 count, viral load, use of PIs, and use of lipid-lowering therapy, hsCRP correlated positively with body mass index, ("bad") non-HDL cholesterol, and triglycerides, while correlating negatively with ("good") HDL cholesterol:
- Body mass index: r = 1.43, 95% confidence interval [CI] 1.15 to 1.75, P = 0.001
- Non-HDL cholesterol: r = 1.49, 95% CI 1.09 to 2.03, P = 0.013
- Triglycerides: r = 1.31, 95% CI 1.05 to 1.60, P = 0.017
- HDL cholesterol: r = 0.77, 95% CI 0.62 to 0.95, P = 0.015
Boger and colleagues listed several limitations to this analysis--lack of fasting lipid measures for all study participants, use of non-HDL cholesterol instead of low-density lipoprotein (LDL) cholesterol, subjective lipoatrophy assessments, and failure to factor in other CVD risk predictors. Still, results do buttress the investigators' hypothesis that traditional CVD markers, like those in the Framingham score, can underestimate heart disease risk in people with well-controlled viremia. The findings also suggest that hsCRP tracks closely with critical lipid quotients and weight.
References
1. Boger M, Shintani A, Mitchell V, et al. Highly-sensitive C-reactive protein (hsCRP) is associated with body mass index and serum lipids in HIV-infected patients with low cardiovascular disease risk and virologic suppression on antiretroviral therapy. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract THPE0160.
2. National Heart, Lung, and Blood Institute. Coronary disease risk prediction score sheet for men based on LDL cholesterol level.
http://www.nhlbi.nih.gov/about/framingham/riskmen.pdf
3. National Heart, Lung, and Blood Institute. Coronary disease risk prediction score sheet for women based on LDL cholesterol level. http://www.nhlbi.nih.gov/about/framingham/riskwom.pdf
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