Risk of cardiovascular disease grew somewhat faster with age in men with HIV than would be expected in the general population, according to results of a 24,000-man analysis.1 But risk of myocardial infarction (heart attack) did not rise faster with age in men with HIV than would be expected in men in the general population.
In the past several years much research has assessed rates of cardiovascular disease in people with HIV infection. For example, two other studies discussed in this issue of HIV Treatment Alerts found that US veterans with HIV and without major heart risk factors had a twice higher heart attack risk than veterans without HIV2 (see "Heart Attack Rate Twice Higher With HIV Among Veterans at Low Risk" in this issue of HIV Treatment Alerts) and that young adults infected with HIV early in life had significantly thicker coronary artery walls -- a possible signal of future heart disease -- than healthy HIV-negative adults3 (see "Heart Artery Walls Thicker in Young Adults With HIV Than in HIV-Negatives" in this issue of HIV Treatment Alerts).
Older age is a major heart disease risk factor in people with and without HIV. Concern about the impact of aging on heart disease in HIV-positive people is growing because people with HIV are now living much longer than they did a few decades ago. But studies comparing cardiovascular disease rates in people with and without HIV can be difficult to interpret if the HIV-positive and negative groups are not similar in age and other key factors. And research has not determined whether the heart disease increase with age is more rapid in people with HIV than in the general population.
Besides traditional cardiovascular risk factors like aging and smoking, people with HIV face two other risk factors -- antiretroviral therapy and the inflammation and immune-system activation caused by HIV itself.
To sort through these cardiovascular risk factors and get a better understanding of how older age adds to heart disease risk in people with HIV, researchers working with the DAD Study group of people receiving treatment for HIV infection conducted this study.1 Their main goal was to calculate the increased risk of cardiovascular disease with each additional year of age in men with HIV and to compare that increase with the age-related rate in men in the general population.
Researchers focused on men in the DAD group, which is an ongoing study of HIV-positive people taking antiretroviral therapy in Europe, the United States, Argentina, and Australia. Medical findings recorded during regular office visits are sent to the central DAD database. DAD researchers also collect basic data like age, gender, and smoking status -- plus HIV-related data like CD4 count, viral load, and antiretrovirals taken.
The research team determined how many cases of cardiovascular disease developed during the study period. They classified each case into one of three groups:
The researchers limited their analysis to HIV-positive men because the low number of cardiovascular diseases that developed in these DAD women during the study period would not support reliable statistical analysis. All of the men had cardiovascular risk data available, and none of the men already had cardiovascular disease before the observation period began. The observation time for each man began when their cardiovascular risk data first got recorded and continued until that man had cardiovascular disease or died, until that man's last study visit plus 6 months, or until February 2011, whichever came first.
The investigators measured age in several ways and used a standard statistical method to pick the measurement that would work best with this group of HIV-positive men. They compared this age-effect measure for HIV-positive men with several cardiovascular risk formulas used for the general population:
Studies like this can measure two types of risk -- absolute risk and relative risk. Absolute risk in a heart disease study is a group's risk of getting heart disease in a given period. Relative risk is the risk of getting heart disease in one group (for example, men with HIV) compared with another group (for example, men without HIV). Because the absolute risk of cardiovascular disease differs by the population studied, the DAD researchers compared the relative increased risk of cardiovascular disease per year of age in DAD men versus the risk per year of age in the three general-population formulas. Specifically, the research team compared the DAD men with the general-population men by measuring the relative risk increase from the age of 40 to the age of 65.
Finally, the researchers calculated how the impact of age on relative risk of cardiovascular disease might be reduced by changing three other risk factors: (1) stopping smoking, (2) lowering cholesterol 18 mg/dL (1 mmol/mL), and (3) lowering systolic blood pressure by 10 mm Hg.
The study included 24,323 men, 59% of them white, 6% nonwhite, and the rest with an unknown race or ethnic background. Median age of the study group stood at 41. Most of these men, 60%, became infected with HIV during sex with another man, 20% became infected during sex with a woman, and 15% became infected when injecting drugs. While 55% of these men smoked at the time of the study, 18% smoked in the past. As a group, these men had taken antiretroviral therapy for a median of 1.9 years. During a median observation time of 6 years, the researchers counted 474 myocardial infarctions (heart attacks), 683 cases of coronary heart disease, and 884 cases of cardiovascular disease (as defined in the bullet list above). The myocardial infarction rate rose from 2.3 per 1000 person-years in 40- to 45-year-old men to 6.5 per 1000 person-years in 60- to 65-year-old men. (A rate of 2.3 per 1000 person-years means about 2 of every 1000 men had a myocardial infarction every year). Coronary heart disease rates climbed from 3.1 per 1000 in 40- to 45-year-olds to 11.9 per 1000 in 60- to 65-year-olds, while cardiovascular disease rates rose from 3.7 per 1000 in 40- to 45-year-olds to 15.9 per 1000 in 60- to 65-year-olds.
The five best age-calculating methods all showed a similar impact of age on risk of heart disease in men with HIV. Compared with a 40-year-old man, a 50-year-old had about a doubled risk of cardiovascular disease (as defined in the bullet list above), a 55-year-old had about a tripled risk, and a 65-year-old had about a 5 times higher risk.
When the researchers compared the age-related increasing risk of myocardial infarction in HIV-positive DAD men with the increasing relative risk in the general population formulas, they found no difference.
But compared with the general population, men with HIV had somewhat faster age-related increases in risk of coronary heart disease and cardiovascular disease. Compared with a 40-year-old HIV-positive man, a 65-year-old man with HIV had a 5.8 times higher relative risk of coronary heart disease (Figure 1). Compared with a 40-year-old man in the general population, a 65-year-old in the general population has a 3.3 to a 4.9 times higher risk of coronary heart disease, depending on the general population formula used. Compared with a 40-year-old HIV-positive man, a 65-year-old man with HIV had a 5.8 times higher relative risk of cardiovascular disease. Compared with a 40-year-old man in the general population, a 65-year-old in the general population has a 4.2 to 4.7 times higher risk of cardiovascular disease, depending on the general population formula used.
Figure 1. Compared with the general population, men with HIV had a somewhat greater increase in risk of coronary heart disease or cardiovascular disease at age 65 compared with age 40.
In men with HIV, stopping smoking, lowering cholesterol, and lowering blood pressure at age 50 would each have a large impact on cardiovascular disease risk by age 65 (Figure 2). Compared with a 40-year-old HIV-positive man, a 65-year-old had a 5.8 times higher cardiovascular disease risk. That age-related increase dropped to 3.0 times if a man stopped smoking at age 50, dropped to 4.8 times if a man lowered his cholesterol 18 mg/dL at age 50, and dropped to 5.2 times if a man lowered his systolic blood pressure 10 mm Hg at age 50.
Figure 2. An HIV-positive man had a 5.8 times higher cardiovascular disease risk at age 65 than at age 40 (cone at far left). But if that man stopped smoking, lowered his cholesterol 18 mg/dL, or lowered his blood pressure 10 mm Hg at age 50, his cardiovascular disease risk increases at age 65 versus 40 were less than 5.8 times.
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