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Lower CD4 count, higher viral load tied to primary MIs in NA-ACCORD
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CROI 2015, February 23-26, 2015, Seattle, Washington
Mark Mascolini
Lower current CD4 count, detectable viral load, a history of clinical AIDS, and traditional cardiovascular risk factors all predicted primary atherosclerotic myocardial infarction (MI) in a large North American cohort, NA-ACCORD [1]. A high rate of secondary MIs, the researchers noted, "emphasizes the need for greater clarity in outcome ascertainment in studies seeking to study the pathogenic role of HIV in atherosclerotic cardiovascular disease."
Although recent research indicates increased risk of atherosclerosis and MI in people with HIV, the precise role of HIV infection in the pathogenesis of atherosclerosis remains unclear, the NA-ACCORD team observed. One reason for the lack of clarity on MI risk with HIV, the researchers speculated, may be failure to classify MIs by type. Type 1 or primary MIs result from atherothrombotic plaque rupture, while type 2 or secondary MIs can be traced a supply-demand mismatch. Some evidence indicates that type 2 MIs are more common in HIV populations [2].
To address these issues, NA-ACCORD investigators determined the incidence of MI by type in an analysis stratified by age. They aimed to calculate frequency and causes of secondary MIs and to examine traditional and HIV-related risk factors for primary MIs. To begin, a physician panel classified potential MIs that occurred in 7 NA-ACCORD cohorts in 1995-2010 as definite, probable, or nonevents. Then they classified definite and probable MIs as primary or secondary. Follow-up ran from baseline (entry to care, cohort inception, or cohort MI observation start date, whichever was latest) until MI diagnosis, death, or administrative censoring. The researchers used Poisson regression to determine adjusted incidence rate ratios for primary MIs with adjustment for relevant baseline and time-updated variables.
The MI search uncovered 271 primary MIs (55%), 219 secondary MIs (45%), and 24,604 cohort members without an MI. Crude incidence rates were 2.68 per 1000 person-years (95% confidence interval [CI] 2.38 to 3.02) for primary MIs and 2.17 per 1000 person-years (95% CI 1.90 to 2.48) for secondary MIs. Primary MI incidence rose with age, from 0.59 per 1000 person-years in people under 40, to 2.5 per 1000 in the 40-to-49 group, to 4.27 per 1000 in the 50-to-59 group, and to 10.12 per 1000 in the 60-to-69 group. Respective rates for secondary MI were 1.15, 2.04, 2.95, and 4.34.
Cohort members under 40 years old accounted for higher proportion of people with a secondary MI than with a primary MI (27% versus 17%). While 87% of the primary MI group were men, 73% of the secondary MI group were men. Proportions of whites in the primary and secondary groups were 59% and 31%, and proportions of blacks 32% and 61%. Men who have sex with men (MSM) accounted for 54% of primary MIs, while MSM made up only 31% of the secondary MI group. Respective proportions of heterosexuals were 22% and 30% and injection drug users 15% and 32%.
Sepsis caused 38% of secondary MIs, followed by illicit drug-induced vasospasm (11%), noncoronary cardiac causes (11%), respiratory failure (9%), hypertensive emergency (5%), procedure-related causes (5%), and anemia (5%).
Numerous classic cardiovascular risk factors predicted primary MI: older age, cigarette smoking, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol, stage 4 or 5 chronic kidney disease, and statin use. After adjustment for traditional risk factors, lower CD4 count, higher viral load, and a history of clinical AIDS independently predicted primary MI, as indicated by the following adjusted incidence rate ratios (aIRR) (and 95% confidence intervals):
-- CD4 count 200-349 vs 500+: aIRR 1.32 (1.01 to 1.73)
-- CD4 count 100-199 vs 500+: aIRR 1.90 (1.40 to 2.58)
-- CD4 count under 100 vs 500+: aIRR 3.03 (2.23 to 4.13)
-- Viral load 400+ copies versus under 400: aIRR 1.56 (1.27 to 1.93)
-- History of clinical AIDS: aIRR 1.26 (1.03 to 1.53)
The NA-ACCORD team believes these HIV-related associations "point to the importance of managing HIV-related risk factors for MI including optimizing ART-mediated viral suppression to prevent progression to lower CD4 nadir and clinical AIDS, as well as to maximize CD4 immune reconstitution."
References
1. Drozd DR, Kitahata MM, Althoff KN, et al. Incidence and risk of myocardial infarction (MI) by type in the NA-ACCORD. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 748.
2. Crane HM, Heckbert SR, Drozd DR, et al. Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts. Am J Epidemiol. 2014;179:996-1005.
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