Genetics make a large contribution to cardiovascular risk for people with HIV

Genetic background has a major impact on the risk of coronary artery disease for people with HIV, results of a large study published in the online edition of Clinical Infectious Diseases show. An unfavourable genetic background increased the risk of coronary artery disease more than some traditional risk factors such as high cholesterol. Treatment with certain antiretroviral drugs including abacavir (Ziagen, also in Kivexa) and lopinavir/ritonavir (Kaletra) also increased the risk.

“Genetic background explained a larger proportion of CAD [coronary artery disease] variability than did diabetes, hypertension or dyslipidemia,” comment the authors. “An unfavorable genetic background had an effect on CAD comparable to certain antiretroviral agents known to increase cardiovascular risk.”

The investigators believe their findings are of clinical significance, and that genetic screening could help identify HIV-positive people with an especially high risk of heart disease.

There is now convincing evidence that HIV infection is associated with an increased risk of coronary artery disease. The precise reasons for this are uncertain. However, traditional risk factors, the inflammatory effects of untreated HIV, immune suppression and the side-effects of some antiretroviral drugs all seem to be significant.

The importance of genetic background to the risk of coronary artery disease in the context of HIV infection is, however, unknown.

An international team of investigators therefore designed a study involving 1875 HIV-positive people enrolled in 24 separate observational studies in Europe, the US, Australia and Argentina. Participants were screened for 23 common single nucleotide polymorphisms (SNPs) known to be associated with an increased risk of coronary artery disease in the general population. The impact of genetic factors on the risk of coronary heart disease was assessed and compared to the contribution of other known risk factors.

The investigators believe their study “represents the most comprehensive genetics-CAD study undertaken in HIV-positive persons”.

The participants received care between 2000 and 2009 and a total of 571 individuals experienced a coronary artery disease event. These people provided cases and the remaining participants were classified as controls.

The patients experiencing cardiovascular events were older than the controls (50 vs 45), and more likely to be current or past smokers (77 vs 69%), to have elevated cholesterol (46 vs 32%), to have diabetes (19 vs 14%), to have a family history of coronary artery disease (28 vs 15%) and to be taking antiretroviral therapy that included abacavir (26 vs 18%).

The investigators divided the participants into four groups (quartiles) according to their number of SNPs associated with coronary artery disease risk. Individuals experiencing a cardiovascular event were significantly more likely to be in the third and fourth quartiles (i.e., greater number of SNPs) than the controls (p = 0.01).

Individuals with the highest number of high-risk SNPs (quartile four) were approximately 50% more likely (p = 0.02) to have experienced a coronary artery event than participants with the fewest high-risk SNPs (quartile one).

The risk of coronary artery disease associated with genetic factors exceeded that associated with hypertension and therapy with abacavir or lopinavir.

The investigators then conducted an analysis to determine the precise contribution of specific factors to the risk of coronary artery disease among their patients.

Age made the single biggest contribution, accounting for 7.5% of risk, followed by current smoking (3.1%), family history (1.9%) and genetic score (0.9%).

However, genetic score made a larger contribution to overall risk of coronary disease than some traditional and HIV-related risk factors, including elevated cholesterol (0.7%), diabetes (0.5%), hypertension (0.5%), current therapy with abacavir (0.5%) and long-term treatment with lopinavir (0.5%).

Adjustment for family history did not affect the association between genetic profile and risk of coronary artery disease.

“Our findings suggest that genetic testing may provide prognostic information complementary to that afforded by family history, traditional risk factors, and antiretroviral regimen,” comment the investigators. “Particularly in high risk patients, knowledge of a deleterious genetic CAD predisposition might further emphasize the rationale for aggressive risk factor modulation and selection of a CAD-neutral antiretroviral regimen to achieve HIV control.”