Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. The present study aimed to clarify this issue. A systematic search of PubMed and Embase was conducted through October 2018. Studies providing risk estimates of NAFLD and mortality were included. A random-effects model was employed to calculate summary risk estimates. Subgroup analyses were performed to identify potential effect modifiers. Fourteen studies, involving 498501 subjects and 24234 deaths, were included. Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without [hazard ratio (HR) = 1.34; 95% confidence interval (CI) 1.17–1.54)]. The significantly positive association between NAFLD and all-cause mortality could not be modified by age, sex, follow-up duration, and adjustment for body mass index, diabetes, smoking or hypertension (all P interaction > 0.05), and remained in sensitivity analyses. No significant associations of NAFLD with CVD (HR = 1.13; 95% CI 0.92–1.38) and cancer (HR = 1.05; 95% CI 0.89–1.25) mortality were found. In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. These findings have important implications for decision making in public health and clinical practice, and highlight the urgency of developing effective treatments for NAFLD.

Background Ultra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population. Methods A population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers. Results After an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36–1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50–1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76–1.17). A nonlinear dose–response pattern was observed for overall cardiovascular and heart disease mortality (all Pnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (all Pinteraction < 0.05). Conclusions High consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.

Objective The association between high-density lipoprotein cholesterol (HDL-C) levels and mortality remains controversial. We aimed to investigate the potential dose–response associations between HDL-C levels and mortality from all causes, cardiovascular disease and cancer in the general population. Methods PubMed and Embase were searched through April 2019. Prospective cohort studies reporting risk estimates of HDL-C levels and mortality were included. Linear and non-linear dose–response analyses were conducted. A random-effects model was employed to calculate pooled hazard ratio. Results Thirty-seven studies, involving 3,524,505 participants and more than 612,027 deaths, were included. HDL-C level was found to be associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response pattern, with the lowest risk observed at HDL-C levels of 54–58 mg/dL, 68–71 mg/dL and 64–68 mg/dL, respectively. Compared with HDL-C level of 56 mg/dL, the pooled hazard ratios for all-cause mortality were 1.03 (95% confidence interval (CI) 1.01, 1.05) and 1.10 (95% CI 1.09, 1.12) for each 10-mg/dL increase and decrease in HDL-C levels, respectively; furthermore, compared with the reference category, the pooled hazard ratios for all-cause mortality were 1.21 (95% CI 1.09, 1.36) and 1.36 (95% CI 1.21, 1.53) for the highest and the lowest categories of HDL-C levels, respectively. Similar results were obtained for cardiovascular and cancer mortality. Conclusions In the general population, HDL-C level is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response manner; both extremely high and low HDL-C levels are associated with an increased risk of mortality.