The role of the metabolic syndrome in HIV

15 October 2006. Related: Conference reports, Side effects, Lipodystrophy and metabolic complications, Lipodystrophy Workshop (IWADRW) 8th San Francisco 2006.

Simon Collins, HIV i-Base

The first session of the Workshop included several presentations and discussions about definition of metabolic syndrome (MS) in HIV-positive patients, and whether this a diagnosis of MS adds to risk greater than the sum of individual markers.

The interest in MS is that it is an equation of several measurable factors that can predict longer-term risk of cardiovascular disease (CVD) and type-2 diabetes mellitus (T2DM) than Framingham which deals with 5 and 10-year risk. Clinical guidelines in Europe and the US for management of pre-diabetes, in non-HIV-related, risk say that individual factors are sufficient to monitor and treat individually, but with HIV these may add more than individual factors alone.

Andrew Carr from St Vincents Hospital, Sidney, reported MS prevalence in the international cohort used for the Lipodystrophy Case Definition Study (approx 800 cases and controls) of 14% by International Diabetes Federation (IDF) and 18% by NCEP ATPIII criteria (National Cholesterol Education Programme, Adult Treatment Panel), [1] which were both less than for the US general population.

The ATPIII definition requires 3 or more factors from: waist (>88cm in women or >102cm in men, triglcerides >1.7 mmol/l, HDL <1.29 mmol/L in women or < 1.04 in men, glucose >6.1 mmol/l, SBP >130 and DBP> 85mmHg. The IDF criteria includes waist >80cm in women and >94cm in men, plus any two other parameters (with glucose set slightly lower at 5.6 mmol/L).

The concordance between the two definitions was significant but only moderate. 23% patients were positive for MS by one or more definition, but only 9% were positive by both (k-0.46, p<0.0001). ATPIII criteria diagnosed 50% more men but 30% fewer women. Half the patients meeting metabolic criteria for MS had a normal waist circumference prevented diagnosis of MS by ATPIII.

Those with MS by either definition had higher BMI, waist:hip ratio, total body fat, visceral fat, systolic and diastolic blood pressure, triglycerides, insulin resistance and diabetes, and lower HDL, as would be expected. Discordance focused on when waist circumference and wasit:hip ratio prevented a diagnosis of MS in 50% of patients with objectively defined lipodystrophy, suggesting that both definitions may be insensitive tools for diagnosing risk of diabetes and cardiovascular disease in HIV-positive patients.

Patients with MS also had higher levels of C-reactive protein (CRP) (5.5 +/-7.0 vs 3.9 +/-6.0 mg/L, p-0.03), lower adiponection (12 +/-8.0 vs 15 +/-10 mmol/L, p=0.04) and high leptin levels (+/-9 vs 4 +/- 6 mmol/L, p<0.0001).

Wand and colleagues from the same research group, also presented data on prevalence, incidence and progression to cardiovascular events or type-2 diabetes (T2DM) over 3 years in a separate cohort of 881 patients. [2]

Prevalence of MS in this group at baseline was 11% and 9% by ATPIII and IDF criteria respectively. In patients without MS at baseline, progression occurred in 32% (ATPIII) and 22% (IDF). Presence of MS at baseline was associated with a significantly increased risk of T2DM after 3 years: ATPIII: RR=4.37 (95CI 2.24-8.52, p<0.001); IDF: RR 2.89 (95CI1.35-6.20, p=0.006). Developing new MS during the study was also associated with higher risk of progression to T2DM, though not as strongly as having MS at baseline.

Relative risk of CVD was 2.58, p=0.051 and 2.97, p=0.026 in the ATPIII and IDF criteria respectively.

The researchers concluded that rapid and frequent progression to MS after starting HAART was associated with development of diabetes (and non-significantly to CVD), and that diagnosis of MS at baseline was therefore a useful tool to identify patients for prevention strategies, especially as the predictive value of individual MS components for diabetes or CVD in this study was low.

References:

1. Samaras K, Wand H, Carr A et al. Metabolic syndrome in HIV-infected patients using IDF and ATPIII criteria: prevalence, discordance and clinical utility. 8th IWADRLH, September 2006, San Francisco. Abstract 1.
2. Wand H, Calmy A, Carey D et al. Metabolic syndrome, cardiovascular disease and type-2 diabetes mellitus after initiation of antiretroviral therapy in HIV-infected adults. 8th IWADRLH, September 2006, San Francisco. Abstract 2.