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Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management.

ABSTRACT: The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary approach to overweight/obesity that may improve outcomes and align with a public health message to combat the growing epidemic of obesity worldwide and to build healthier lives free of cardiovascular diseases.

SUBMITTER: Neeland IJ

PROVIDER: S-EPMC5875734 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management.

Neeland Ian J IJ Poirier Paul P Després Jean-Pierre JP

Circulation 20180301 13

The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue result ...[more]

PMID: 29581366

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Project description:BackgroundThe association between metabolic syndrome and increased cardiovascular disease (CVD) risk is well-established. However, in patients with incident CVD, the relationship between obesity, metabolic health, and subsequent CVD and mortality outcomes are less well-established. This study investigated the association between body mass index (BMI), metabolic health and the risk of subsequent cardiovascular mortality and morbidity outcomes in patients with incident CVD events.MethodsThis cohort study identified 130 685 patients from the nationwide Clinical Practice Research Datalink (CPRD GOLD) and Hospital Episode Statistics (HES) databases in the United Kingdom. Patients were ≥18 years with incident CVD [coronary heart disease (CHD), stroke, or peripheral vascular disease (PVD)] between 1 January 1998 and 31 December 2017. BMI (in kg/m2 ) was categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obese (≥30). Within each BMI category, patients were grouped by increasing count of 1, 2 or 3 metabolic risk factors [RF] (dyslipidaemia, diabetes mellitus and hypertension) and were regarded as metabolically unhealthy while absence of these factors was considered metabolically healthy (MH). Multivariable Cox regression was used to assess the risk (hazard ratio with 95% confidence interval) of subsequent outcomes (non-fatal CHD, stroke, PVD, incident heart failure, CVD-mortality and all-cause mortality) in BMI subgroups with incremental count of metabolic RFs.ResultsDuring a median follow-up of 13.0 years, a higher BMI was associated with reduced risk for stroke, PVD, CVD-mortality and all-cause mortality within each metabolic risk category, while increasing metabolic RFs within each BMI subgroup accounted for increasing risks. When compared with patients with normal BMI and no RF, CVD-mortality risk in overweight patients with no RF was 0.76 (0.70-0.84), and in obese patients with no RF was 0.85 (0.76-0.96). The respective risk for all-cause mortality in patients with overweight and no RF was 0.69 (0.65-0.72), and in obese patients with no RF was 0.75 (0.70-0.79). Subsequent outcomes of stroke and PVD showed similar trends. In contrast, the risk of subsequent non-fatal CHD events and incident HF increased with higher BMI and with incremental metabolic risk factors within each BMI category. Underweight was constantly associated with increased risk for all outcomes regardless of the presence of metabolic RFs except for non-fatal CHD events.ConclusionsIn patients with incident CVD, overweight and obesity were related to a more favourable prognosis for subsequent stroke, PVD and mortality (CVD-related and all-cause) irrespective of the presence of other metabolic risk factors.

Dataset Information

Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management.

Publications

Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management.

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