Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women

Caleyachetty, Rishi; Thomas, G. Neil; Toulis, Konstantinos; Mohammed, Nuredin; Gokhale, Krishna; Kumarendran, Balachandran; Nirantharakumar, Krishnarajah

doi:10.1016/j.jacc.2017.07.763

Cited by 392 publications

(318 citation statements)

References 39 publications

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“…Besides, MUHNO showed a higher cardiovascular risk than obese with a normal metabolic profile, reinforcing the importance of the metabolism beyond obesity. Several studies have observed an increased risk of cardiovascular disease and all‐cause mortality in MHO . However, other studies have shown that cardiovascular risk did not rise in obese phenotype with health status .…”

Section: Discussionsupporting

confidence: 71%

The effects of metabolic status on non‐alcoholic fatty liver disease‐related outcomes, beyond the presence of obesity

Ampuero¹,

Aller²,

Gallego‐Durán³

et al. 2018

Aliment Pharmacol Ther

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Summary Background Metabolically healthy obesity (MHO) shows a reduced risk compared with obese patients with adverse metabolic conditions. Lean people suffering some metabolic derangements also have non‐alcoholic fatty liver disease (NAFLD)‐related outcomes compared with non‐obese subjects with a few metabolic risks. Aim To define the impact of the metabolic status on the NAFLD‐related outcomes, beyond the presence of obesity. Methods We designed a multicentre cross‐sectional study, including 1058 biopsy‐proven NAFLD patients. Metabolically healthy status was strictly defined by the lack of metabolic risk factors (diabetes mellitus, low HDL, hypertriglyceridemia, arterial hypertension). Non‐alcoholic steatohepatitis (NASH) and significant fibrosis (F2‐F4) were identified by liver biopsy. Chronic kidney disease epidemiology collaboration equation was calculated for kidney function and the atherogenic index of plasma (AIP) for cardiovascular risk. Results Metabolically healthy (OR 1.88; P = 0.050) and unhealthy obesity (OR 3.47: P < 0.0001), and unhealthy non‐obesity (OR 3.70; P < 0.0001) were independently associated with NASH together with homeostatic model assessment (HOMA), ALT, and platelets. Significant fibrosis was more frequently observed in the presence of adverse metabolic conditions in obese (OR 3.89; P = 0.003) and non‐obese patients (OR 3.92; P = 0.002), and independently associated with platelets, albumin, ALT, HOMA, and age. The number of metabolic factors determined the risk of NASH and significant fibrosis. Glomerular filtration rate was lower in unhealthy (91.7 ± 18) than healthy metabolism (95.6 ± 17) (P = 0.007). AIP was higher in adverse metabolic conditions (P = 0.0001). Metabolically unhealthy non‐obesity showed higher liver damage (NASH 55.8% vs 42.4%; P < 0.05; significant fibrosis 31.7% vs 11.4%; P < 0.0001) and cardiovascular risk (P < 0.0001) than healthy obesity. Conclusions Metabolic unhealthy status showed a greater impact on NASH, significant fibrosis, kidney dysfunction, and atherogenic profile than obesity. However, metabolically healthy obesity was not a full healthy condition. We should focus our messages especially on patients with adverse metabolic conditions.

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Section: Discussionsupporting

confidence: 71%

The effects of metabolic status on non‐alcoholic fatty liver disease‐related outcomes, beyond the presence of obesity

Ampuero¹,

Aller²,

Gallego‐Durán³

et al. 2018

Aliment Pharmacol Ther

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show abstract

“…However, a recent large sample study with a short follow-up period (median of 5.4 years) revealed that MHO individuals had a higher risk of coronary heart disease, cerebrovascular disease and heart failure than MHNW individuals. 27 This suggests that obesity is a risk factor for CVD events, regardless of the presence or absence of metabolic syndrome; metabolic syndrome is no more valuable than BMI for identifying individuals at risk. This is similar to the current finding that a metabolically healthy profile did not completely protect people with obesity from incident CVD events.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular disease outcomes in metabolically healthy obesity in communities of Beijing cohort study

Chen

Wang

et al. 2018

Int J Clin Pract

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Summary Objective The objective of this study was to investigate the association between metabolically healthy obese (MHO) phenotype and the risk of cardiovascular disease (CVD). Methods A total of 9393 subjects aged ≥40 years were enrolled in the cohort study (2011‐2015). The participants were stratified by body mass index category and metabolic risk at baseline, and incidence of CVD was ascertained at follow‐up. Results The MHO accounted for 6.7%. Compared with the metabolically healthy normal weight (MHNW) group, MHO subjects demonstrated increased risk of CVD events (HR = 1.91; 95% CI, 1.13‐3.24). In people with obesity, there was no significant difference on increasing risk of incidence of CVD in the metabolically unhealthy individuals compared with metabolically healthy individuals (HR = 1.19; 95% CI, 0.74‐1.91). Female (OR = 1.97; 95% CI, 1.06‐3.64), smoking (OR = 2.09; 95% CI, 1.06‐4.10), a larger waist circumference (OR = 1.07; 95% CI, 1.03‐1.10) and higher LDL cholesterol levels (OR = 1.55; 95% CI, 1.20‐2.00) were independent risk factors of the development of the MHO to the metabolically unhealthy obese (MUO) phenotype. Conclusions The risk of CVD events of MHO phenotypes is similar to MUO phenotypes; both are higher than the MHNW phenotypes.

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“…The greater risk of CVD in obesity are well established, and thus, the discussion here is brief . Compared with normal‐weight individuals, even those with metabolically healthy obesity have been shown to have a higher chance of developing coronary heart disease (HR = 1.49) and heart failure (HR = 1.96) . Collectively, abdominal obesity may be a strong catalyst in promoting the early onset of CVD .…”

Section: Obesity and Age‐related Diseasesmentioning

confidence: 99%

Obesity and ageing: Two sides of the same coin

2020

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Summary Conditions and comorbidities of obesity mirror those of ageing and age‐related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are “two sides of the same coin” through discussing how obesity predisposes an individual to age‐related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early‐onset of chronic diseases in obesity parallel those of ageing.

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Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women

Cited by 392 publications

References 39 publications

The effects of metabolic status on non‐alcoholic fatty liver disease‐related outcomes, beyond the presence of obesity

The effects of metabolic status on non‐alcoholic fatty liver disease‐related outcomes, beyond the presence of obesity

Cardiovascular disease outcomes in metabolically healthy obesity in communities of Beijing cohort study

Obesity and ageing: Two sides of the same coin

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