Both traditional risk factors and biomarkers associated with cardiovascular disease in patients with HIV

Family history and smoking are the strongest predictors of cardiovascular disease in patients with HIV, US investigators report in the online edition of AIDS. They also found that biomarkers associated with clotting and endothelial dysfunction – damage to the cells lining blood vessels – were significantly associated with an increased risk of outcomes such as heart attack and stroke.

“Our findings support an aggressive approach in identifying significant family history and targeting traditional cardiac risk factors for therapeutic intervention,” comment the investigators.

They also believe that their results have implications for the routine care of patients with HIV, and suggest that biomarkers that indicate an increased risk of cardiovascular disease should be monitored in high-risk patients.

There is now a large body of research showing that patients with HIV have an increased risk of cardiovascular disease. A number of factors are thought to contribute to this, including a high prevalence of traditional risk factors, and the side-effects of some antiretroviral drugs.

The SMART treatment-interruption study showed that individuals taking a break from their HIV therapy had an increased risk of non-HIV-related illnesses, including cardiovascular disease. Subsequent analysis of its findings showed that biomarkers D-dimer and interleukin-6 (IL-6) were elevated in those taking a break from therapy, suggesting that HIV replication was causing clotting and inflammation.

US investigators wished to further examine the contribution of these factors to the risk of cardiovascular disease in patients with HIV.

They therefore identified 52 HIV-positive patients who had experienced a cardiovascular event when enrolled in a National Institute of Allergy and Infectious Diseases study between 1995 and 2009.

On a two-to-one basis, patients who had experienced a cardiovascular event (cases) were matched with those who had not (controls).

The investigators then compared the prevalence of traditional risk factors for cardiovascular disease between these two groups, as well as levels of certain biomarkers.

Analyses were then undertaken to determine the factors associated with cardiovascular events after four months and two years of follow-up.

At baseline, there was a significantly higher prevalence of some traditional risk factors for cardiovascular disease in the cases than the controls. These included dyslipidaemia (87 vs 72%, p = 0.05), smoking (49% vs 25%, p = 0.004), and a family history of such diseases (30% vs 11%, p = 0.003).

After four months of follow-up, both total and LDL cholesterol were higher in cases than controls (p = 0.02 and p = 0.04 respectively), and after two years, the cases had significantly higher levels of glucose (p = 0.03).

Viral load at the four-month follow-up was significantly lower amongst the patients who experienced events than those who did not (2500 copies/ml vs 14000 copies/ml, p = 0.04). Neither the duration nor the type of antiretroviral therapy differed between the two groups.

CD14 cell counts, an indicator of inflammation, were higher in the cases than the controls at the four-month follow-up point (p = 0.04).

As regards biomarkers, levels of D-dimer (a marker for thrombosis, or clotting) were higher in the cases than the controls at both the four-month (p = 0.003) and two-year (p = 0.04) follow-ups. Similarly, VCAM (an indicator of endothelial activation) was higher in cases than controls at both these times (p = 0.02 and p = 0.03 respectively).

TIMP-1, another indicator of endothelial function, was elevated in cases after four months (p = 0.02).

The investigators then performed a series of statistical analyses to see which factors were independently associated with an increased risk of cardiovascular diseases.

After four months of follow-up, levels of D-dimer (p = 0.02), family history (p = 0.006), current smoking (p = 0.004), and total cholesterol (p = 0.0005) were all significant risk factors.

After two years, a family history of a premature heart attack (p = 0.03), D-dimer (p = 0.006), and glucose (p = 0.001) were all associated with an increased risk of a cardiovascular event.

The investigators comment, “although the strongest contributors were traditional cardiovascular disease risk factors such as smoking and high cholesterol (CVD), markers of innate immune activation, endothelial cell dysfunction, and thrombosis were also related to CVD events.”