Risk Factors for Premature Myocardial Infarction: A Systematic Review and Meta-analysis of 77 Studies.

OBJECTIVE: To evaluate the magnitude of the association between risk factors and premature myocardial infarction (MI) (men aged 18-55 years; women aged 18-65 years). PATIENTS AND METHODS: We searched MEDLINE and other databases from inception through April 30, 2020, as well as bibliography of articles selected for data extraction. We selected observational studies reporting the magnitude of the association of at least 1 risk factor (demographic characteristics, lifestyle factors, clinical risk factors, or biomarkers) with premature MI and a control group. Pooled risk estimates (random effects) from all studies unadjusted and adjusted for risk factors were reported as summary odds ratios (ORs) with 95% CIs. RESULTS: From 35,320 articles of 12.7 million participants, we extracted data on 19 risk factors from 77 studies across 58 countries. Men had a higher risk of premature MI (OR, 2.39; 95% CI, 1.71 to 3.35) than did women. Family history of cardiac disease was associated with a higher risk of premature MI (OR, 2.67; 95% CI, 2.29 to 3.27). Major modifiable risk factors associated with higher risk were current smoking (OR, 4.34; 95% CI, 3.68 to 5.12 vs no/former), diabetes mellitus (OR, 3.54; 95% CI, 2.69 to 4.65), dyslipidemia (OR, 2.94; 95% CI, 1.76 to 4.91), and hypertension (OR, 2.85; 95% CI, 2.48 to 3.27). Higher body mass index carried higher risk (OR, 1.46; 95% CI, 1.24 to 1.71 for ≥25 kg/m2 vs <25 kg/m2). Biomarkers associated with 2- to 3-fold higher risk were total cholesterol levels greater than 200 mg/dL, triglyceride levels higher than 150 mg/dL, and high-density lipoprotein cholesterol levels less than 60 mg/dL (to convert to mmol/L, multiply by 0.0259). CONCLUSION: Major risk factors for premature MI are mostly amenable to patient, population, and policy level interventions. Mild elevations in body mass index and triglyceride levels were associated with higher risk, which has implications for the growing worldwide epidemic of cardiometabolic diseases.

Can Patients Trust Online Health Information? A Meta-narrative Systematic Review Addressing the Quality of Health Information on the Internet.

BACKGROUND: The Internet has become a leading source of health information accessed by patients and the general public. It is crucial that this information is reliable and accurate. OBJECTIVES: The purpose of this systematic review was to evaluate the overall quality of online health information targeting patients and the general public. METHODS: The systematic review is based on a pre-established protocol and is reported according to the PRISMA statement. Eleven databases and Internet searches were performed for relevant studies. Descriptive statistics were used to synthesize data. The NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the methodological quality of the included studies. RESULTS: Out of 3393 references, we included 153 cross-sectional studies evaluating 11,785 websites using 14 quality assessment tools. The quality level varied across scales. Using DISCERN, none of the websites received a category of excellent in quality, 37-79% were rated as good, and the rest were rated as poor quality. Only 18% of websites were HON Code certified. Quality varied by affiliation (governmental was higher than academic, which was higher than other media sources) and by health specialty (likely higher in internal medicine and anesthesiology). CONCLUSION: This comprehensive systematic review demonstrated suboptimal quality of online health information. Therefore, the Internet at the present time does not provide reliable health information for laypersons. The quality of online health information requires significant improvement which should be a mandate for policymakers and private and public organizations.

Cholangiocyte autophagy contributes to hepatic cystogenesis in polycystic liver disease and represents a potential therapeutic target.

Polycystic liver disease (PLD) is a group of genetic disorders with limited treatment options and significant morbidity. Hepatic cysts arise from cholangiocytes exhibiting a hyperproliferative phenotype. Considering that hyperproliferation of many cell types is associated with alterations in autophagy, we hypothesized that autophagy is altered in PLD cholangiocytes, contributes to hepatic cystogenesis, and might represent a potential therapeutic target. We employed functional pathway cluster analysis and next-generation sequencing, transmission electron microscopy, immunofluorescence confocal microscopy, and western blotting to assess autophagy in human and rodent PLD cholangiocytes. A three-dimensional culture model was used to study the effects of molecular and pharmacologic inhibition of autophagy on hepatic cystogenesis in vitro, and the polycystic kidney disease-specific rat, an animal model of PLD, to study the effects of hydroxychloroquine, a drug that interferes with the autophagy pathway, on disease progression in vivo. Assessment of the transcriptome of PLD cholangiocytes followed by functional pathway cluster analysis revealed that the autophagy-lysosomal pathway is one of the most altered pathways in PLD. Direct evaluation of autophagy in PLD cholangiocytes both in vitro and in vivo showed increased number and size of autophagosomes, lysosomes, and autolysosomes; overexpression of autophagy-related proteins (Atg5, Beclin1, Atg7, and LC3); and enhanced autophagic flux associated with activation of the cAMP-protein kinase A-cAMP response element-binding protein signaling pathway. Molecular and pharmacologic intervention in autophagy with ATG7 small interfering RNA, bafilomycin A1 , and hydroxychloroquine reduced proliferation of PLD cholangiocytes in vitro and growth of hepatic cysts in three-dimensional cultures. Hydroxychloroquine also efficiently inhibited hepatic cystogenesis in the polycystic kidney disease-specific rat. CONCLUSION: Autophagy is increased in PLD cholangiocytes, contributes to hepatic cystogenesis, and represents a potential therapeutic target for disease treatment. (Hepatology 2018;67:1088-1108).