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Framingham Score May Underestimate CHD Risk With HIV, HCV, and HIV/HCV
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20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
Risk of coronary heart disease (CHD) calculated by the Framingham Risk Score (FRS) was lower in HIV-positive men in a US veterans cohort than in veterans without HIV, a finding suggesting FRS underestimates CHD risk in people with HIV [1]. Results of this analysis also suggested that FRS underestimates CHD risk in people with hepatitis C virus (HCV) infection.
Clinicians and researchers routinely use FRS to predict 10-year risk of CHD, but some work suggests it underestimates CHD risk in people with HIV, who have risk factors not included in the score. US investigators hypothesized that FRS may also underestimate CHD risk in people with HCV infection, because two of its components--total cholesterol and systolic blood pressure--tend to be reduced in HCV-infected people. (The score includes age, gender, total cholesterol, HDL cholesterol, smoking, systolic blood pressure, and antihypertensive therapy.) The researchers planned this analysis to evaluate FRS performance in four mutually exclusive groups: people with HCV only, people with HIV only, people with HIV and HCV, and people with neither infection.
This retrospective study relied on data from the national Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES) from 2001 through 2009. The investigators matched HCV-infected veterans 1-to-1 with HCV-uninfected veterans by age, sex, race, and year of HCV diagnosis. They defined HIV coinfection as an HIV diagnosis recorded in the year of HCV diagnosis. They limited the analysis to men from 20 to 79 years old, without baseline cardiovascular disease or diabetes, and with data allowing calculation of FRS.
After those exclusions the researchers had 115,639 HCV-only men, 1798 HIV-only men, 3058 men with HCV/HIV, and 122,397 with neither virus. Age across the four groups (HCV, HIV, HCV/HIV, uninfected) averaged 52.6, 49.1, 49.9, and 52.4 (P = 0.0001). More than half of men with HCV alone (56.2%) or neither virus (55%) were white, while more than half with HIV alone (51.5%) or HCV/HIV (58.6%) were black.
Compared with uninfected men, the groups with HCV, HIV, and HCV/HIV included higher proportions with a drug abuse history (P = 0.000), and men with HCV or HCV/HIV had a higher proportion of alcohol abusers (P = 0.000) (see poster linked below for data). Total cholesterol was significantly lower in all three infected groups than in uninfected controls (P = 0.0001). Current smoking rates were highest in the HCV/HIV group (68.8%) and the HCV group (66.4%), lower in the HIV group (55.1%), and lowest in the uninfected group (49.8%) (P = 0.000).
Overall, veterans with HCV (with or without HIV) had two favorable CHD risk characteristics (lower total cholesterol and "bad" LDL cholesterol) and three unfavorable traits (higher alanine aminotransferase and higher proportions of alcohol and drug abusers); they also had lower proportions on lipid-lowering therapy. Compared with the control group, veterans with HIV were slightly younger and had lower body mass index and lower systolic blood pressure, but they also lower "good" HDL cholesterol.
Median FRS in points and in risk percent were higher and equivalent in uninfected men and HCV-infected men, and lower and equivalent in men with HIV and HCV/HIV (P = 0.0001 for both comparisons).
Median FRS score and FRS risk percent:
-- Uninfected men: 13 and 12%
-- HCV only: 13 and 12%
-- HIV only: 11 and 8%
-- HCV/HIV: 11% and 8%
When the researchers divided FRS-predicted CHD risk into high (greater than 20% heart attack risk in 10 years), medium (10% to 20% risk), and low (less than 10% risk), the uninfected group virtually matched the HCV-only group (about 15% high risk and 50% medium risk) (see figure in poster linked below). In the same analysis, CHD risk in the HIV-only group mirrored risk in the HCV/HIV Group (about 9% high risk and 40% medium risk).
Because 10-year CHD risk scores were similar in the uninfected and HCV group, and in the HIV and HCV/HIV group, the researchers proposed that "routine clinical assessment with the FRS would thus suggest CHD risk is unaffected by HCV status." But that seems unlikely because research indicates that HCV infection boosts the risk of cardiovascular disease.
Why does FRS appear to miscalculate cardiovascular risk in people with HCV and HCV/HIV? The researchers suggested that (1) low total cholesterol in these groups may be offset by higher smoking rates and (2) high prevalence of drug abuse (a CHD risk factor) in HCV-infected people is not factored into the FRS equation. "Given the higher prevalence of CHD risk factors and potential independent contribution of HCV infection to CHD risk," the researched concluded, "the FRS may underestimate risk in HCV-infected persons."
FRS indicated a lower risk of CHD in HIV-positive veterans than in veterans with neither HIV nor HCV, even though people with HIV typically run a higher heart disease risk than the general population. That questionable FRS prediction may reflect the younger age of HIV-positive people, the investigators suggested, but it may also mean FRS underestimates CHD risk in HIV-positive people.
The population studied and the comparison method influence this kind of analysis. A much smaller study of US patients (239 with HIV, 167 with HCV, and 182 with HCV/HIV) compared FRS in those groups with the general-population NHANES cohort [2]. In this study people with HIV/HCV or HCV had a higher FRS-predicted CHD risk than the general population. On the other hand, a 2006 D:A:D analysis found higher myocardial infarction rates in this HIV cohort than FRS would predict in five subgroups reflecting different lengths of antiretroviral use [3].
References
1. Chew K, Bhattacharya D, McGinnis K, et al. Coronary heart disease risk by Framingham risk score in hepatitis C virus and HIV/hepatitis C virus. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 716. http://www.retroconference.org/2013b/PDFs/716.pdf
2. Kakinami L, Block RC, Adams MJ, Cohn SE, Maliakkal B, Fisher SG. Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population. Int J Clin Pract. 2013;67:6-13.
3. Law MG, Friis-Moller N, El-Sadr WM, et al. The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study. HIV Med. 2006;7:218-230.
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