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CLINICAL RESEARCH: METABOLIC SYNDROME AND RISK

Insulin Resistance, the Metabolic Syndrome, and Risk of Incident Cardiovascular Disease

A Population-Based Study

Jørgen Jeppesen, MD, DMSc^_*,_*, Tine W. Hansen, MD, PhD^,, Susanne Rasmussen, MD, PhD, Hans Ibsen, MD, DMSc^_*, Christian Torp-Pedersen, MD, DMSc and Sten Madsbad, MD, DMSc

^_* Department of Medicine, Glostrup University Hospital, Glostrup, Denmark
Research Center for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
Department of Endocrinology and Internal Medicine, Hvidovre University Hospital, Hvidovre, Denmark

Manuscript received August 18, 2006; revised manuscript received January 19, 2007, accepted January 22, 2007.

^_* Reprint requests and correspondence: Dr. Jørgen Jeppesen, Department of Medicine, Glostrup University Hospital, Ndr. Ringvej, DK-2600 Glostrup, Denmark. (Email: jj{at}heart.dk).

Objectives: The goal was to clarify if insulin resistance (IR) would predict cardiovascular disease (CVD) independent of the metabolic syndrome (MetSyn).

Background: Although the cause of MetSyn is not well defined, IR has been proposed to be an important cause. Only a small number of population-based studies have sought to clarify if IR predicts CVD independent of MetSyn.

Methods: This was a prospective Danish population-based study of 2,493 men and women, age 41 to 72 years, without major CVD at baseline. We defined MetSyn according to both the International Diabetes Foundation (IDF) and the National Cholesterol Education Program (NCEP) criteria, and we quantified IR by the homeostasis model assessment (HOMA-IR). Prevalence of MetSyn was 21% according to IDF criteria and 16% according to NCEP criteria. Accordingly, we defined IDF-HOMA-IR as belonging to the highest 21% of the HOMA-IR distribution, and NCEP-HOMA-IR as belonging to the highest 16% of the HOMA-IR distribution.

Results: Over a median follow-up of 9.4 years, the incidence of CV end points (CV death, nonfatal ischemic heart disease, and nonfatal stroke) amounted to 233 cases. In proportional hazard models, adjusting for age, gender, smoking, and low-density lipoprotein cholesterol, and with IDF-HOMA-IR and IDF-MetSyn included in the same model, the relative risk of an end point was 1.67 (95% confidence interval [CI] 1.22 to 2.29) for IDF-HOMA-IR and 1.16 (95% CI 0.84 to 1.60) for IDF-MetSyn. The corresponding figures for NCEP-HOMA-IR and NCEP-MetSyn included in the same model were 1.49 (95% CI 1.07 to 2.07) and 1.56 (95% CI 1.12 to 2.17).

Conclusions: In this Danish study, both HOMA-IR and NCEP-MetSyn were independent predictors of incident CVD.

Abbreviations and Acronyms   BMI = body mass index   CI = confidence interval   CVD = cardiovascular disease   HDL-C = high-density lipoprotein cholesterol   HOMA = homeostasis model assessment   HR = hazard ratio   IDF = International Diabetes Foundation   IR = insulin resistance   LDL-C = low-density lipoprotein cholesterol   MetSyn = metabolic syndrome   NCEP = National Cholesterol Education Program

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