A prospective study in Finland has shown that the metabolic syndrome of insulin resistance, raised lipids, abdominal fat accumulation and raised blood pressure is associated with an increased risk of cardiovascular disease after a median of eleven and half years follow-up. The findings were published in the December 4 edition of the Journal of the American Medical Association.
Metabolic syndrome has been reported to affect almost one-third of middle-aged Americans without HIV infection, and bears a close resemblance to the lipodystrophy syndrome seen in people with HIV, although the fat wasting seen in HIV patients is not a characteristic of the HIV-negative metabolic syndrome, whilst the polycystic ovary syndrome seen in non-HIV metabolic syndrome has not been reported in women with HIV-related metabolic syndrome.
The constellation of metabolic abnormalities defined as the metabolic syndrome may be present in around 40% of HIV-positive people on antiretroviral therapy.
The Finnish study compared the ability of different definitions of metabolic syndrome to predict death from cardiovascular disease or other causes.
The metabolic syndrome as defined by the National Cholesterol Education Programme was three or more of the following: fasting plasma glucose of at least 110 mg/dL (6.1 mmol/L), serum triglycerides of at least 150 mg/dL (1.7 mmol/L), serum HDL cholesterol less than 40 mg/dL (1.04 mmol/L), blood pressure of at least 130/85 mm Hg, or waist girth of more than 102 cm (40 inches).
The metabolic syndrome for men according to the World Health Organisation was defined as hyperinsulinemia or elevated fasting glucose and at least two of the following: abdominal obesity, dyslipidemia, or hypertension. Insulin resistance was estimated as hyperinsulinemia based on fasting insulin levels in the upper fourth. Impaired fasting glycemia was defined as fasting blood glucose of 101-109 mg/dL (5.6-6.0 mmol/L). Diabetes was defined as blood glucose of at least 110 mg/dL (6.1 mmol/L) or a clinical diagnosis of diabetes with dietary, oral, or insulin treatment. Abdominal obesity was defined according to the original WHO definition (waist-hip ratio greater than 0.90 or Body Mass Index equal or greater than 30) and the European Group for the Study of Insulin Resistance recommendation (waist girth equal or greater than 94 cm [37 inches]).
“Men with the metabolic syndrome as defined by the NCEP were 2.9 to 4.2 times more likely and, as defined by the WHO, 2.9 to 3.3 times more likely to die of coronary heart disease after adjustment for conventional cardiovascular risk factors”, the researchers said.
There were 109 deaths during the follow-up period, of which 46 were attributable to cardiovascular disease. The cohort were aged between 42 years and 60 years at baseline.
The baseline prevalence of the metabolic syndrome in the 1209 person cohort was low in comparison with a US survey – between 9 and 14% depending on definition, compared to 30% in the Third National Health and Nutrition Survey, reported earlier this year.
A recent Italian report suggests that the frequency of metabolic syndrome – using a definition in most respects more severe than the WHO or NCEP definitions – is higher in HIV-positive individuals on HAART than in middle-aged US males. The review of 201 patients found that 40% had the metabolic syndrome, compared to 6% of an HIV-negative age-matched control group.
The findings are likely to add to concerns that a substantial proportion of people with HIV now on antiretroviral therapy could develop cardiovascular disease or die from heart disease rather than HIV-related illnesses. At last month's Sixth International Congress on Drug Therapy in HIV Infection, which took place in Glasgow, Dr Jens Lundgren of the University of Copenhagen argued that it would not be possible to tell for some time whether this risk is real, due to the lag time between the onset of the metabolic syndrome, inclduing cholesterol elevations, and cardiovascular events.
References
Lakka HM et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288: 2709-2716, 2002.
Ford ES et al. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287: 356-359, 2002.