Nonoverweight nonalcoholic fatty liver disease and incident cardiovascular disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is known as a risk of incident cardiovascular disease (CVD). About 20% of NAFLD occurs in nonobese individuals. However, it remains to be elucidated the association between nonoverweight with NAFLD and a risk of incident CVD. Therefore, we investigated the risk of nonoverweight with NAFLD for incident CVD.We performed a post-hoc analysis of the previous prospective cohort study, in which 1647 Japanese were enrolled. Abdominal ultrasonography was used to diagnose NAFLD. Overweight was defined as body mass index ≥23 kg/m2, which is recommended by World Health Organization for Asian. We divided participants into 4 phenotypes by existence of NAFLD and/or overweight. The hazard risks of the 4 phenotypes for incident CVD were calculated by Cox hazard model after adjusting for age, sex, smoking status, exercise, hypertension, hyperglycemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol at baseline examination.Incident proportions of CVD were 0.6% in nonoverweight without NAFLD, 8.8% in nonoverweight with NAFLD, 1.8% in overweight without NAFLD, and 3.3% in overweight with NAFLD. Compared with nonoverweight without NAFLD, the adjusted hazard ratios of incident CVD were 10.4 (95% confidence interval 2.61–44.0, P = .001) in nonoverweight with NAFLD, 1.96 (0.54–7.88, P = .31) in overweight without NAFLD, and 3.14 (0.84–13.2, P = .09) in overweight with NAFLD.Nonoverweight with NAFLD was associated with higher risk of incident CVD. We should pay attention to NAFLD, even in nonoverweight individuals, to prevent further CVD events.

Non‐obese fatty liver disease is associated with lacunar infarct

“…27 A prospective cohort study in Japan showed that the hazard ratio of incident cardiovascular disease (including stroke) of non-overweight individuals with fatty liver disease was higher than that of overweight individuals with fatty liver disease. 28 In a similar context, another study showed that non-obese subjects with fatty liver disease have a higher overall mortality than subjects with fatty liver disease who are overweight or obese. 29 One plausible explanation for this result is that fatty liver disease influences the occurrence of lacunar infarct in non-obese individuals.…”

“…Compared with obese fatty liver disease, non‐obese fatty liver disease is known to be associated with comparable histological phenotypes, such as steatohepatitis and fibrosis, although the metabolic profile is more favourable . A prospective cohort study in Japan showed that the hazard ratio of incident cardiovascular disease (including stroke) of non‐overweight individuals with fatty liver disease was higher than that of overweight individuals with fatty liver disease . In a similar context, another study showed that non‐obese subjects with fatty liver disease have a higher overall mortality than subjects with fatty liver disease who are overweight or obese .…”

Non-invasive Quantification of Fat Deposits in Skeletal Muscle Predicts Cardiovascular Outcome in Kidney Failure

“…Classically defined by body-mass index, overweight and obesity are heterogeneous conditions, with important interindividual differences in risk factor profiles despite similar amounts of total body fat, including in the CKD population (Stenvinkel et al, 2013). Anthropometric measures such as waist circumference and waist-to-hip ratio and, more recently, novel imaging techniques contributed to demonstrate the critical role of regional fat distribution in the development of metabolic alterations and CVD (Pou et al, 2007;Liu et al, 2010Liu et al, , 2011Therkelsen et al, 2013;Yoshitaka et al, 2017;Neeland et al, 2018Neeland et al, , 2019Okamura et al, 2019;Tanaka et al, 2019). In Illustrative longitudinal data of fat distribution, residual kidney function, and serum p-cresyl sulfate levels from two individuals on long-term PD: a 39-year-old woman on PD for 4 years (patient 1) and a 66-year-old man on PD for 5 years (patient 2).…”

<p>A Pilot Study Assessing the Possible Combined Effect of Physical Activity and <em>PNPLA3</em> rs738409 Polymorphism on the Risk for Non-Alcoholic Fatty Liver Disease in the Japanese Elderly General Population</p>

“…3,25 In Japan, normal-weight subjects account for 50% of the total NAFLD population, and 15.2% of the normal-weight population are diagnosed with NAFLD. 3 Normal-weight individuals with NAFLD are more likely to have insulin resistance, type 2 diabetes and cardiovascular diseases than those without NAFLD, 3,4 and they appear to have different characteristics compared to overweight or obese patients with NAFLD, such as a different distribution of visceral adipose tissue, recent increase in body weight, intake of a high-cholesterol diet and a characteristic genetic background. 25 Our recent longitudinal study conducted in a Japanese general population showed that the PNPLA3 rs738409 genotypes are associated with the risk of NAFLD, especially in normal-weight subjects.…”

“…nonalcoholic steatohepatitis, hepatic cirrhosis and liver cancer) but also metabolic diseases, including type 2 diabetes and cardiovascular disease (CVD). [2][3][4][5] NAFLD patients are frequently obese/overweight and/or suffer from type 2 diabetes, and insulin resistance is a key pathogenic trigger. [1][2][3] In addition, aging is an important factor affecting the association between obesity, NAFLD and these-related complications, 6,7 and early interventions are required to effectively manage correctable metabolic risk factors (e.g.…”