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Viral Load Over 50 and Low CD4/CD8 Ratio Hoist MI Risk in French Cohort
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12th European AIDS Conference, November 11-13, 2009, Cologne, Germany
Mark Mascolini
A viral load above 50 copies independently raised the risk of myocardial infarction (MI) as much as 60% in a French case-control comparison headed by Dominique Costagliola [1]. And every 1-unit higher CD4/CD8 ratio independently halved the MI risk. Several traditional cardiovascular risk factors were also at play in this study of people with heart attacks from 2000 to 2006.
Costagliola picked cases and controls from 74,958 HIV-infected people followed in the French Hospital Database on HIV. MI incidence in that database stands at 1.24 per 1000 person-years. The 289 cases were people with a first definite or probable MI during prospective follow-up from January 2000 through December 2006. The 884 controls were HIV-infected people without an MI matched to cases for age, gender, and care at the same center as the case when the MI occurred. The investigators divided cases and controls into three groups:
· HDL population: 151 cases and 316 controls with complete data--used to figure the best way to build models to assess the impact of different risk factors
· Overall population: 278 case and 873 controls, all of whom had a CD4/CD8 ratio
· Complete data population: 252 cases and 744 controls without missing data (except family history) among the variables identified through the HDL population: smoking status, family history, hypertension, high cholesterol, cocaine and/or injecting drug use, high glucose, viral load, and CD4/CD8 ratio
After the variable-defining analysis in the HDL population, Costagliola and coworkers devised two models to study the complete data population and the overall population. The first model included the number of traditional cardiovascular risk factors, cocaine and/or injecting drug use, viral load below or above 50 copies, and the CD4/CD8 ratio. The second model considered all these risk factors one by one. The investigators adjusted all analyses for exposure to every antiretroviral.
In the first model, four factors independently predicted MI in the overall population and/or the complete population:
· Every additional traditional risk factor: odds ratio [OR] 2.3, P < 0.001 in the overall population; OR 1.6, P < 0.001 in the complete population
· Cocaine and/or injecting drug use (versus no use): OR 1.6, P = 0.088 in the overall population; OR 1.5, P = 0.040 in the complete population
· Viral load above 50 copies (versus at or below 50): OR 1.3, P = 0.092 in the overall population; OR 1.4, P = 0.015 in the complete population
· CD4/CD8 ratio per unit: OR 0.5, P = 0.005 in the overall population; OR 0.6, P = 0.014 in the complete population
An AIDS diagnosis, CD4 count, and CD4 nadir had no impact on MI risk in this model.
In the second model, eight factors independently predicted MI in the overall population and/or the complete population:
· Smoking (versus no smoking): OR 4.1, P < 0.001 in the overall population; OR 4.8, P < 0.001 in the complete population
· High cholesterol: OR 2.5, P < 0.001 in the overall population; OR 2.5, P < 0.001 in the complete population
· Cocaine and/or injecting drug use: OR 1.8, P = 0.043 in the overall population; OR 1.7, P = 0.100 in the complete population
· Hypertension: OR 1.7, P = 0.024 in the overall population; OR 1.7, P = 0.042 in the complete population
· Glucose at or above 5.45 mmol/L: OR 1.6, P = 0.042 in the overall population; OR 1.6, P = 0.058 in the complete population
· Viral load above 50 copies: OR 1.4, P = 0.068 in the overall population; OR 1.6, P = 0.025 in the complete population
· CD4/CD8 ratio per unit: OR 0.5, P = 0.012 in the overall population; OR 0.6, P = 0.060 in the complete population
· Missing family history of premature coronary artery disease: OR 0.3, P < 0.001 in the overall population; OR 0.3, P < 0.001 in the complete population
The CD4/CD8 ratio and viral load results support previous findings that a good and consistent response to antiretroviral therapy lowers the risk of heart disease [2-5], even though individual antiretrovirals may heighten cardiovascular risk. The CD4/CD8 ratio, often used to reckon immune system strength, is above 1 in healthy people. In this analysis, every 1-unit increase in the CD4/CD8 ratio (a doubling of CD4 cells per the same number of CD8 cells) halved the risk of an MI. Costagliola noted that the correlation between this ratio and MI was not the most robust predictor in this analysis, "but it's available for everyone, and it's cheap, so use it," she counseled.
Several traditional risk factors, especially smoking and lofty cholesterol, proved the most potent predictors of MI in the French cohort. The finding that a missing family history cuts the MI risk does not mean physicians should hope patients don't mention their fathers' heart attacks. Rather, Costagliola suggested, it indicates that family heart disease history was not routinely collected by HIV clinicians--an oversight that should be remedied.
References
1. Lang S, Mary-Krause M, Cotte L, et al. Impact of traditional cardiovascular risk factors and HIV parameters on the risk of myocardial infarction: a case-control study nested within NHDH ANRS CO4. 12th European AIDS Conference. November 11-13, 2009. Cologne, Germany. Abstract PS11/2.
2. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283-2296.
3. Data Collection on Adverse Events of Anti-HIV Drugs Study Group, Sabin CA, d'Arminio Monforte A, Friis-Moller N, et al. Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction. Clin Infect Dis. 2008;46:1101-1110.
4. Lichtenstein KA, Buckner K, Armon C, et al. CD4+ T-cell counts <350 cells/mm3 are a risk factor for cardiovascular disease in the HIV Outpatient Study. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract THPE0236.
5. Baker JV, Peng G, Rapkin J, et al. CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS. 2008;22:841-848.
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