icon-    folder.gif   Conference Reports for NATAP  
  17th CROI
Conference on Retroviruses
and Opportunistic Infections
San Francisco CA
February 16-19, 2010
Back grey_arrow_rt.gif
D-Dimer But Not hsCRP Predicts Impending Cardiovascular Disease in Case-Control Study
  17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
D-dimer, the coagulation marker that leapt to prominence when SMART researchers linked it to a high risk of non-AIDS death [1], predicted impending cardiovascular problems in a case-control study by Emily Ford and colleagues at the National Institute of Allergy and Infectious Diseases (NIAID) [2]. But a much-studied inflammation marker, hsCRP, did not predict heart disease in this analysis.
The NIAID team focused on 52 HIV-infected people who had a new cardiovascular diagnosis or procedure from among 1921 people enrolled in NIAID HIV protocols from 1995 through 2009. The biggest proportion of cases involved myocardial infarction (MI) (25), followed by coronary revascularization (14), and silent MI (4).
The investigators matched these cases with 104 controls who did not have new cardiovascular disease or procedure while in the NIAID cohorts. Cases and controls were similar in age (average 50.8 years in both groups), proportion of men (98% in both groups), proportion of African Americans (19.2% of cases and 14.4% of controls), years of follow-up (average 8.2 and 8.6), years of HIV infection (average 13.4 and 14.0), lowest-ever CD4 count (average 209 and 229), highest-ever viral load (average 4.3 and 5.4 log, P = 0.40), body mass index 4 months before the cardiovascular event (average 25.6 kg/m(2) in both groups), years of antiretroviral exposure (average 8.9 and 8.4), years of protease inhibitor exposure (average 3.7 and 4.0), proportion with HCV (13.5% in both groups), proportion with a smoking history (58.8% and 52.5%), and proportion with diabetes (15.4% and 12.7%).
The 52 people with a new cardiovascular problem differed from controls in several respects: proportion with dyslipidemia (87% versus 71.9%, P = 0.05), proportion of current smokers (49% versus 25%, P = 0.004), and proportion with a family history of MI (29.8% versus 10.9%, P = 0.003). There was a strong trend toward more frequent antihypertensive use in cases than controls (38.5%versus 24.0%, P = 0.06).
Four months before the cardiovascular event, cases had significantly higher total cholesterol (average 212 versus 188 mg/dL, P = 0.002) and dangerous low-density lipoprotein cholesterol (130 versus 116 mg/dL, P = 0.04). Viral load was lower in cases than controls 4 months before their cardiovascular complication (P = 0.04). Two years before the event, cases had significantly higher glucose (average 115 versus 102 mg/dL, P = 0.03).
D-dimer concentrations were significantly higher in cases than controls 4 months before their cardiovascular event (average 482 versus 315 ng/mL, P = 0.003) and 2 years before (average 505 versus 260 ng/mL, P = 0.04). Vascular cell adhesion molecule 1 (VCAM-1, which controls the adhesion of lymphocytes, monocytes, eosinophils, and basophils to artery walls) was significantly higher in cases than controls 4 months before their cardiovascular setback (P = 0.02). But hsCRP readings did not differ significantly between cases and controls 4 months or 2 years before the cardiovascular event. Nor did levels of IL-6 or other inflammation markers measured.
Statistical analysis considering multiple cardiovascular risk factors identified three that independently inflated that risk 2 years before the event--elevated D-dimer (P = 0.006), high glucose (P = 0.001), and family history of premature MI (P = 0.03). Independent predictors of cardiovascular disease measured 4 months before the event were elevated D-dimer (P = 0.02), family history of premature MI (P = 0.006), current smoking (P = 0.004), and high total cholesterol (P = 0.0005).
Ford and colleagues suggested their findings "support an aggressive approach in obtaining pertinent family history and targeting traditional cardiac risk factors for therapeutic interventions such as dyslipidemia and smoking cessation as well as the potential addition of biomarkers such as D-dimer in further stratification of high-risk patients."
1. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050203.
2. Ford E, Richterman A, Thompson W, et al. Elevated D-dimer but not CRP levels in HIV+ patients prior to incident myocardial infarction or other cardiovascular disease event. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 713. http://www.retroconference.org/2010/PDFs/713.pdf.