BACKGROUND:
Metabolic syndrome,
insulin resistance and diabetes are associated with an increased risk of
cardiovascular disease.
Niacin is known to increase
insulin resistance, and have adverse effects on
blood glucose levels, but to have beneficial effects on plasma
lipids and
lipoproteins. We therefore aimed to determine whether intensive
lipid therapy with a
niacin-containing regimen would have a beneficial effect on
cardiovascular disease, despite an expected increase in plasma
glucose and
insulin resistance in subjects with the
metabolic syndrome,
insulin resistance or abnormal fasting plasma
glucose levels. METHODS: The effect of three years' treatment with
niacin plus
simvastatin (N+S) on both angiographic and clinical outcomes were analyzed in the 160 subjects with
coronary artery disease (CAD) and low levels of
high density lipoproteins (HDL) from the HDL-
Atherosclerosis Treatment Study (HATS). A subgroup analysis was performed on the basis of: (1) the presence or absence of the
metabolic syndrome, (2) higher or lower
insulin resistance, and (3) the presence or absence of impaired fasting
glucose or diabetes (dysglycemia). Individuals classified as having the MS, increased
insulin resistance or dysglycemia would be expected to have increased cardiovascular risk. RESULTS: N+S reduced the change in mean proximal percent
stenosis (Δ%S) compared to placebo (PL) in subjects with the
metabolic syndrome (Δ%Sprox 0.3 vs 3.0, p=0.003) and in the more
insulin resistant group of subjects (Δ%Sprox 0.5 vs 2.7, p=0.001), while subjects with dysglycemia (impaired fasting
glucose or diabetes) showed a lesser benefit (Δ%Sprox 1 vs 3.2, p=0.13). These changes occurred despite increased in-treatment fasting
glucose levels (3%), fasting
insulin (19%) and decreased
insulin sensitivity (-10%). Overall primary clinical events were reduced by 60% with N+S compared to PL (p=0.02). A similar reduction of the rate of primary events was seen in patients with
metabolic syndrome,
insulin resistance, and to a lesser extent in patients with dysglycemia in the N+S group compared to PL. CONCLUSIONS: These data indicate that, in CAD patients with low HDL, treating the atherogenic
dyslipidemia with a combination of N+S leads to substantial benefits in terms of
stenosis progression and clinical events, independently of whether the patient has the
metabolic syndrome or is
insulin resistant. Over a 3 year period, the beneficial effect of
niacin in combination with
simvastatin appears to offset the modest adverse effect of
niacin on
glucose metabolism and
insulin resistance in at higher risk patients, as long as careful attention is paid to
glycemic control.