Metabolic syndrome as common in HIV-negative as in HIV-positive individuals

New evidence suggests that metabolic syndrome is no more prevalent in HIV-positive patients than in HIV-negative individuals of similar sex, age and race in the midwest of the United States. The results were published in the March 1^st edition of Clinical Infectious Diseases.

“Metabolic syndrome” is defined as having three or more of the following characteristics:

• obesity (waist circumference ≥102cm for men, ≥88cm for women)
• high fasting triglyceride levels (≥150mg/dl)
• low HDL cholesterol levels (
• high fasting glucose levels (100-125mg/dl)
• high blood pressure (≥130/80mm Hg, or currently on blood pressure medication)

Many specific antiretroviral medications (particularly protease inhibitors) are known to lead to elevated triglycerides and/or LDL cholesterol, elevated blood glucose, and lowered HDL cholesterol. Many studies have shown that metabolic syndrome is more common in HIV-positive people on potent antiretroviral therapy than in HIV-positive people not on medication. Yet it has also been suggested that these rates may be no greater than those seen in the general population.

In this prospective, cross-sectional study, researchers from St. Louis, Missouri, compared 471 patients at a Midwestern US HIV outpatient clinic to 471 HIV-negative ‘controls’. Patient data were collected between January and July 2005. The controls were chosen randomly from the US National Health and Nutrition Examination Survey (NHANES; 2001-2002) cohort, but matched one-to-one with the study subjects by age (within three years – mean, 40.1 years), sex (65% male), race (61% black), and smoking status (42% smokers).

Metabolic syndrome – risk and risk factors

Of the 471 HIV-positive clinic patients, 381 (81%) had at least one of the criteria for metabolic syndrome; 120 (26%) had ‘full-fledged’ metabolic syndrome with three or more criteria met. This was extremely close to the rate of metabolic syndrome found in the matched HIV-negative cohort (27%).

Multivariate analysis found that the only statistically significant predictors of metabolic syndrome in the HIV-positive group were: older age (43.4 vs. 39.0 years), higher CD4 cell count (542 vs. 417 cells/mm³), white race (47% vs. 34% black), and a higher weight-to-height ratio (known as body mass index) (BMI – 31.3 vs. 25.8) (p

Although both groups had similar overall rates of metabolic syndrome, their characteristics were quite different. The HIV-positive group were more likely to have lower HDL cholesterol (44 % vs. 30%) and high triglycerides (44% vs. 25%). The HIV-negative control individuals were more likely to have oversized waists (44% vs. 31%) and high glucose levels (31% vs. 22 %) (p ≤ 0.001 for all).

There were also differences by race and sex among HIV-positive people with metabolic syndrome. Men were more likely to be older (45.1 vs. 39.9 years), white (58% vs. 23%), on anti-HIV therapy (84% vs. 53%), and to have high triglycerides (295.2 vs. 165.7) than women (p ≤ 0.01 for all). Among African-Americans, women had thicker waists than men, but men had higher triglycerides and glucose and lower HDL levels than women.

Implications

The researchers concluded that, “although we found a high prevalence of metabolic syndrome among HIV-infected patients, this diagnosis was strongly associated with traditional cardiovascular risk factors rather than HAART-related effects. Additional longitudinal studies are needed to determine whether metabolic syndrome is equally predictive of future diabetes and heart disease in HIV-infected persons compared with HIV-uninfected persons.”

In an accompanying editorial commentary, Clara Y. Jones of Tufts University states that ‘[m]etabolic syndrome has been assumed to be more common in HIV-infected persons because of the true increase in [its] components… such as increased blood sugar level and diabetes [and] increased lipid levels”. As to the seeming contradictions between this and previous studies, she notes: “This study did not controvert the evidence that metabolic complications increase… after initiating HAART… but showed that the estimated level of increased risk of metabolic syndrome… is not significantly greater than the risk in HIV-uninfected persons of the same age, race, sex, and smoking status. The findings do not diminish the potential importance of addressing the risk factors in individual patients”.

Antiretroviral use

Use and type of antiretroviral therapy did not result in a significant difference in metabolic syndrome; current protease inhibitor use predicted only increased triglyceride levels (p= 0.03), as did any history of stavudine (d4T) use (p= 0.05). HDL cholesterol levels were likely to be higher with NNRTI use (p