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Serum insulin and incident coronary heart disease in middle-aged British men
I J Perry1, S G Wannamethee, P H Whincup
1Department of Public Health, Royal Free Hospital School of Medicine, London, England.
Insights
Elevated insulin levels, or hyperinsulinemia, are linked to increased coronary heart disease risk, particularly in men. This association persists even after adjusting for factors like HDL cholesterol, suggesting insulin may be atherogenic.
Area of Science:
- Cardiovascular Epidemiology
- Metabolic Syndrome Research
Background:
- Previous studies have not definitively established a link between elevated circulating insulin and coronary heart disease (CHD).
- Limitations in prior research include the use of non-specific insulin assays and insufficient adjustment for confounding factors like high-density lipoprotein (HDL) cholesterol.
Purpose of the Study:
- To investigate the independent relationship between serum insulin concentration and major coronary disease events.
- To address limitations of previous studies by using a specific insulin assay and adjusting for HDL cholesterol.
Main Methods:
- Analysis of non-fasting serum insulin levels in 5,550 men (aged 40-59) from the British Regional Heart Study using a specific enzyme-linked immunoadsorbent assay (ELISA).
- Prospective follow-up for 11.5 years to record major coronary disease events (fatal and non-fatal myocardial infarction).
- Statistical analysis included age-adjusted and multivariate proportional hazards models, adjusting for various risk factors.
Main Results:
- A nonlinear association was observed between serum insulin and coronary disease events, with a nearly twofold increased risk in the highest insulin decile.
- The association remained significant after adjusting for multiple risk factors, including HDL cholesterol (adjusted RR = 1.6).
- Similar associations were found in subgroups, including those with and without baseline coronary disease and with lower baseline glucose levels.
Conclusions:
- The findings support the hypothesis that hyperinsulinemia is atherogenic and may act with a threshold effect.
- The nonlinear association and attenuation in multivariate analysis suggest elevated insulin may also serve as a marker for common etiologic factors shared with non-insulin-dependent diabetes mellitus.
Abstract:
Earlier studies have not resolved the question of whether elevated circulating insulin levels are independently related to the development of coronary heart disease. Previous studies have not used a specific insulin assay and in all but a minority of studies that have addressed this issue it has not been possible to adjust for possible confounding due to high density lipoprotein (HDL) cholesterol. The authors examined the relation between serum insulin concentration and major coronary disease events (fatal and non-fatal myocardial infarction) in the British Regional Heart Study. The data are based on 5,550 men (aged 40-59 years) in 18 towns whose baseline, non-fasting serum samples were analyzed for insulin using a specific enzyme-linked immunoadsorbent assay (ELISA) method. Known diabetics were excluded. At 11.5 years of follow-up, 521 major coronary disease events had occurred, 261 fatal and 260 non-fatal. A nonlinear relation between serum insulin and coronary disease events was observed with an almost twofold increased relative risk in the 10th decile of the serum insulin distribution (> or = 33.8 mU/liter) relative to the 1st to the 9th deciles combined (age-adjusted relative risk (RR) = 1.9, 95% confidence interval (CI) 1.6-2.4). There was some attenuation of this association on cumulative adjustment for a wide range of biologic and life-style coronary disease risk factors, including HDL cholesterol, though it remained significant in the fully adjusted proportional hazards model (RR = 1.6, 95% CI 1.1-2.3). Similar associations between insulin and coronary disease events were seen in men with and without evidence of coronary disease at screening and in men with baseline serum glucose below the 80th percentile. These data are consistent with the hypothesis that a high level of serum insulin (hyperinsulinemia) is atherogenic, with a threshold effect. However, the markedly nonlinear form of the association and the attenuation in multivariate analysis strongly suggest that elevated insulin levels may only be a marker for common etiologic factors in the development of both coronary disease and non-insulin-dependent diabetes mellitus.