Risk of myocardial infarction and heart failure among metabolically healthy but obese individuals. The HUNT Study, Norway

Mørkedal B, Vatten LJ, Romundstad PR, et al.
J Am Coll Cardiol. 2013 Dec 14. doi: 10.1016/j.jacc.2013.11.035. [Epub ahead of print]

Background

Obesity is associated with increased risk of acute myocardial infarction (AMI) and heart failure (HF) [1,2]. Obesity negatively affects metabolic factors such as blood pressure, glucose tolerance and blood lipids, which is associated with cardiovascular disease [3].
It remains as yet unclear whether the increased risk associated with obesity is attributable to those metabolic abnormalities, with effects beyond these negligible, as suggested in one study [4].
This prospective study of a large population-based cohort aimed to assess obesity in relation to risks of AMI and HF, and distinguished between metabolically healthy and unhealthy obesity. 61299 Norwegian participants of 20 years and older were enrolled in the Nord-Trøndelag health study (HUNT-2). Of 27196 individuals information on BMI was available from an earlier screening and the HUNT-1 study (~10 and 30 years before the baseline of HUNT-2). 10059 (16.4%) of 61299 participants were classified as obese (BMI≥30 kg/m2) and 15576 (25.4 %) as metabolically unhealthy (elevated waist circumference or BMI ≥30 kg/m2 in addition to at least two of the following: elevated non-fasting triglycerides, reduced HDL cholesterol, elevated blood pressure or use of blood pressure medication, elevated non-fasting glucose or if diagnosed with diabetes). 34.6% of the obese participants were metabolically healthy.

Main results

• Age- and sex-adjusted HR for AMI among obese men and women who were metabolically healthy was 1.0 (95%CI: 0.8-1.2) as compared to normal weight (BMI<25) and metabolically healthy participants. Obese and metabolically unhealthy participants had HR: 1.7 (95%CI: 1.5-1.9). A contrast in risk of AMI between metabolically healthy and unhealthy participants was seen, regardless of BMI value.
• Neither long term obesity nor recently developed obesity was associated with substantial excess risk for AMI among metabolically healthy participants. Metabolically unhealthy participants had a consistently higher risk for AMI.
• Age- and sex-adjusted HR for HF among obese men and women who were metabolically healthy was 1.6 (95%CI: 1.3-2.0) as compared to normal weight and metabolically healthy individuals. Obese and metabolically unhealthy participants had HR: 1.7 (95%CI: 1.4-2.0). The risk of HF was positively associated with BMI, and a particularly high risk was seen among the severely obese, while differences in metabolic status were negligible.
• Long-lasting obesity was associated with a stronger risk of HF, regardless of metabolic status, as compared to normal weight and metabolically healthy participants. Metabolically healthy participants who had recently developed obesity, also had a higher risk of HF.
• When waist-hip ratio was used to indicate abdominal obesity, results were similar to the primary analyses using BMI.

Conclusion

This prospective study showed that among metabolically healthy participants without known cardiovascular disease at baseline, obesity does not confer substantial excess risk of AMI as compared to normal weight individuals. The risk of AMI in metabolically unhealthy individuals was however much higher than of metabolically healthy participants, across the whole range of BMI.
In contrast, obesity seems more important than metabolic factors for the development of HF; risk of HF was similarly increased in metabolically healthy and unhealthy obese participants, compared to metabolically healthy normal-weight individuals. The association with HF was specifically strong for severe obesity (>40 kg/m2) and for long-term obesity, and did not differ much with metabolic status.

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