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Original Investigation |

Myocardial Infarction and Ischemic Heart Disease in Overweight and Obesity With and Without Metabolic Syndrome

Mette Thomsen, MD1,2; Børge G. Nordestgaard, MD, DMSc1,2
[+] Author Affiliations
1Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital
2Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
JAMA Intern Med. 2014;174(1):15-22. doi:10.1001/jamainternmed.2013.10522.
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Importance  Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown.

Objective  To test the hypothesis that overweight and obesity with and without metabolic syndrome are associated with increased risk of MI and IHD.

Design, Setting, and Participants  We examined 71 527 individuals from the Copenhagen General Population Study and categorized them according to body mass index (BMI) as normal weight, overweight, or obese and according to absence or presence of metabolic syndrome.

Main Outcomes and Measures  Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome.

Results  During a median of 3.6 years’ follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1.81-3.00) in obese individuals with metabolic syndrome. For IHD, results were similar but attenuated. Normal weight vs overweight vs obesity and presence vs absence of metabolic syndrome did not interact on risk of MI or IHD (P = .90 and P = .44). Among individuals both with and without metabolic syndrome there were increasing cumulative incidences of MI and IHD from normal weight through overweight to obese individuals (log-rank trend P = .006 to P < .001). Although the multivariable adjusted hazard ratio for MI in individuals with vs without metabolic syndrome was 1.54 (95% CI, 1.32-1.81) across all BMI categories, addition of metabolic syndrome to a multivariable model including BMI and other clinical characteristics improved the Harell C-statistic only slightly for risk of MI (comparison P = .03) but not for IHD (P = .41).

Conclusions and Relevance  These findings suggest that overweight and obesity are risk factors for MI and IHD regardless of the presence or absence of metabolic syndrome and that metabolic syndrome is no more valuable than BMI in identifying individuals at risk.

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Figure 1.
Distribution of Body Mass Index (BMI) According to the Absence or Presence of Metabolic Syndrome

Data are based on 71 527 individuals from the Copenhagen General Population Study without prior diagnoses of ischemic heart disease. Dashed lines indicate divisions between the categories of BMI (calculated as weight in kilograms divided by height in meters squared) (normal weight, 18.5-24.9; overweight, 25.0-29.9; obese, ≥30.0).

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Figure 2.
Cumulative Incidences of (Left) Myocardial Infarction (MI) and (Right) Ischemic Heart Disease (IHD) as a Function of Age According to Body Mass Index (BMI) Category (Normal Weight, Overweight, Obese) and Absence or Presence of Metabolic Syndrome

A, The hazard ratios (HRs) for MI vs normal weight individuals were 1.38 (95% CI, 1.14-1.67) in overweight and 2.04 (95% CI, 1.64-2.54) in obese individuals (log-rank trend P < .001). B, The HRs for IHD vs normal weight individuals were 1.25 (95% CI, 1.12-1.40) and 1.64 (95% CI, 1.44-1.86). C, The HR for MI in individuals with vs without metabolic syndrome was 1.54 (95% CI, 1.32-1.81). D, The HR for IHD in individuals with vs without metabolic syndrome was 1.38 (95% CI, 1.26-1.52). Data are based on 71 527 individuals from the Copenhagen General Population Study without prior diagnoses of IHD. Hazard ratios were adjusted for age, sex, smoking, plasma low-density lipoprotein cholesterol level, lipid-lowering medication use (statins for approximately 97% of participants receiving such medication), aspirin use, and physical inactivity. Body mass index was calculated as weight in kilograms divided by height in meters squared.

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Figure 3.
Risk of Myocardial Infarction and Ischemic Heart Disease According to Combinations of Body Mass Index (BMI) Category (Normal Weight, Overweight, Obese) and Absence or Presence of Metabolic Syndrome

A, All participants; B, stratified by sex. Based on 71 527 individuals from the Copenhagen General Population Study without prior diagnoses of ischemic heart disease. Hazard ratios were adjusted for age, sex, smoking, plasma low-density lipoprotein cholesterol level, lipid-lowering medication use (statins for approximately 97% of participants receiving such medication), aspirin use, and physical inactivity. Body mass index was calculated as weight in kilograms divided by height in meters squared. Error bars indicate 95% confidence interval. HR indicates hazard ratio; IHD, ischemic heart disease; MI, myocardial infarction.

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