Clinical implications of renin-angiotensin system inhibitors for development and progression of non-alcoholic fatty liver disease.

Recently, there has been an increasing interest in the therapeutic efficacy of RAS inhibitors (RASi) in patients with non-alcoholic fatty liver disease (NAFLD) because they may reduce oxidative stress, inflammatory markers, and enhanced fibrosis. An objective of this study was to investigate the role of RASi on NAFLD development and progression in a large cohort. We conducted a nested case-control study. Study subjects were classified into two study cohorts according to baseline NAFLD status: non-NAFLD (n = 184,581) and established NALFD (n = 27,565). An NAFLD development or progression case was defined as a patient with newly developed NAFLD or new progression of advanced fibrosis from non-NAFLD and established NALFD cohorts, respectively. A conditional logistic regression analysis was conducted to estimate the associations between RASi exposure and NAFLD development/progression. Overall, no significant association was evident between RASi use and NAFLD development or progression (NAFLD development; ever-user vs. never-user: OR 1.017; 95% CI 0.842-1.230, NAFLD progression; ever-user vs. never-user: aOR 0.942; 95% CI 0.803-1.105). RASi ever-use in cases of individuals who were obese or who had normal fasting plasma glucose (FPG) was associated with reduced risk of both NAFLD development (body mass index (BMI) ≥ 25 kg/m2: 0.708 [95% confidence interval (CI) 0.535-0.937], FPG of < 100 mg/mL: 0.774 [95% CI 0.606-0.987]) and progression (BMI ≥ 25 kg/m2: 0.668 [95% CI 0.568-0.784], FPG of < 100 mg/mL: 0.732 [95% CI 0.582-0.921]). The present study did not verify a significant overall association between RASi use and NAFLD development/progression but suggested that RASi might prevent NAFLD development and progression among specific subjects.

Metabolic Syndrome and Parkinson's Disease Incidence: A Nationwide Study Using Propensity Score Matching.

Background: Metabolic syndrome (MetS) and Parkinson's disease (PD) share common pathophysiological mechanisms. This study aimed to investigate the influence of MetS on PD incidence. Materials and Methods: A propensity score-matched cohort study was conducted using the National Health Insurance Service-National Health Screening Cohort (NHIS-HealS) data (2002-2015) from the Korean National Health Insurance Service. Individuals with MetS were identified from those who underwent a health checkup in 2009-2010 and were 1:1 matched to individuals without MetS (non-MetS) using the propensity score method. Among 314,737 eligible individuals, 85,530 MetS and non-MetS pairs were selected. Results: During a mean follow-up of 7.23 years, 819 (0.48%) PD cases occurred. Individuals with MetS exhibited 1.23 times greater PD incidence (95% confidence interval [CI], 1.06-1.43; P = 0.006). The risk of PD increased with the number of MetS components, with the presence of five MetS components altogether doubling the incidence of PD (odds ratio [OR], 2.00; 95% CI, 1.30-3.04; P = 0.001). High blood pressure, low high-density lipoprotein cholesterol, and high fasting blood glucose increased PD incidence by 1.34 times (95% CI, 1.15-1.58; P < 0.001), 1.31 times (95% CI, 1.13-1.52; P < 0.001), and 1.20 times (95% CI, 1.04-1.38; P = 0.013), respectively. Elevated waist circumference was not associated with PD incidence (OR, 1.11; 95% CI, 0.96-1.28; P = 0.176). High triglycerides exerted a protective effect against PD incidence especially in men (OR, 0.66; 95% CI, 0.54-0.81; P < 0.001). Conclusions: MetS may be a risk factor for PD incidence, and individual components of MetS exert different effects depending on sex.

Do renin-angiotensin system inhibitors reduce risk for hepatocellular carcinoma?: A nationwide nested case-control study.

BACKGROUND: To date, there has been a renewed interest in renin-angiotensin system inhibitors (RASi) for HCC prevention because they may reduce potent angiogenic factors. OBJECTIVES: This study set out to investigate associations between RASi use and HCC development. METHODS: We conducted a nested case-control study. A case was defined as a patient who was newly diagnosed with HCC. We selected 567 cases and controls using 1:1 propensity score matching. RASi exposure was classified into ever-user and never-user, then categorized according to cumulative dose and prescription period. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for HCC incidence according to RASi use were analyzed. RESULTS: Overall, no significant association was found between exposure to RASi and HCC incidence (ever-user vs. never-user: aOR, 0.77; 95% CI, 0.56-1.07). In subgroup analysis, women receiving RASi ≥30 cumulative defined daily doses (cDDDs) showed significantly lower aORs (0.49; 95% CI, 0.24-0.95. Angiotensin II receptor blockers only-use ≥30 cDDD was significantly associated with reduced risk of HCC (aOR, 0.65; 95% CI, 0.43-0.97). In cases where subjects did not have diabetes mellitus and where the cDDD of RASi was 1800 or more, the risk of HCC development was significantly reduced compared to that in subjects with no RASi exposure (aOR, 0.26; 95% CI, 0.08-0.72). CONCLUSION: The present study did not verify a significant overall association between RASi use and HCC but indicated lower HCC incidence in some subgroups. The possibility of a beneficial effect at a higher cumulative RASi dose was also presented.