Metabolic syndrome is associated with similar long-term prognosis in those living with and without obesity: an analysis of 45 615 patients from the nationwide LIPIDOGRAM 2004-2015 studies.

We aimed to evaluate the association between metabolic syndrome (MetS) and long-term all-cause mortality. The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006, and 2015. MetS was diagnosed based on the National Cholesterol Education Program, Adult Treatment Panel III (NCEP/ATP III), and Joint Interim Statement (JIS) criteria. The cohort was divided into four groups: non-obese patients without MetS, obese patients without MetS, non-obese patients with MetS, and obese patients with MetS. Differences in all-cause mortality were analysed using Kaplan-Meier and Cox regression analyses. A total of 45 615 participants were enrolled (mean age 56.3, standard deviation: 11.8 years; 61.7% female). MetS was diagnosed in 14 202 (31%) by NCEP/ATP III criteria and 17 216 (37.7%) by JIS criteria. Follow-up was available for 44 620 (97.8%, median duration 15.3 years) patients. MetS was associated with increased mortality risk among the obese {hazard ratio, HR: 1.88 [95% confidence interval (CI) 1.79-1.99] and HR: 1.93 [95% CI 1.82-2.04], according to NCEP/ATP III and JIS criteria, respectively} and non-obese individuals [HR: 2.11 (95% CI 1.85-2.40) and 1.7 (95% CI 1.56-1.85) according to NCEP/ATP III and JIS criteria, respectively]. Obese patients without MetS had a higher mortality risk than non-obese patients without MetS [HR: 1.16 (95% CI 1.10-1.23) and HR: 1.22 (95% CI 1.15-1.30), respectively in subgroups with NCEP/ATP III and JIS criteria applied]. MetS is associated with increased all-cause mortality risk in non-obese and obese patients. In patients without MetS, obesity remains significantly associated with mortality. The concept of metabolically healthy obesity should be revised. Metabolic syndrome (MetS) is used to describe a constellation of metabolic disturbances such as elevated blood glucose, increased levels of triglycerides and decreased level of high density lipoprotein cholesterol. They are often accompanied by elevated blood pressure and central obesity, defined as increased waist circumference. Usually, those metabolic disturbances occur in obese individuals, but sometimes, they can also occur in lean subjects. This relatively recent concept is often referred to as lean MetS. A key conclusion from our paper is that MetS, when it occurs in lean patients, is associated with similarly unfavourable long-term prognosis as in obese patients. Additionally, our analysis shows that lean patients with MetS are less often treated with lipid-lowering drugs despite having higher low density lipoprotein cholesterol levels (LDL-C). An additional finding, which is important from a public health perspective, is that obese patients who do not fulfil MetS criteria have higher long-term all-cause mortality than their lean counterparts without MetS. This finding should be an argument to encourage maintenance of normal body weight.

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Conflict of interest: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.J. and M.B. have received an unrestricted educational grant from Valeant and have served as consultants or speakers for Valeant. P.P. owns four shares in AstraZeneca PLC and has received honoraria and/or travel reimbursement for events sponsored by AKCEA, Amgen, AMRYT, Link Medical, Mylan, Napp, and Sanofi. All other authors declare no conflicts of interest concerning the results of this analysis. All authors revised the article critically for important intellectual content. All authors gave final approval of the work, have participated sufficiently in the work, and take public responsibility for appropriate portions of the content.