?-Glutamyltransferase Variability and the Risk of Mortality, Myocardial Infarction, and Stroke: A Nationwide Population-Based Cohort Study.
ABSTRACT: Although it has been suggested that the ?-glutamyltransferase (GGT) level is an indicator of cardiometabolic disorders, there is no previous study to evaluate the implication of GGT variability on the development of myocardial infarction (MI), stroke, all-cause mortality, and cardiovascular disease (CVD)-related mortality. GGT variability was measured as the coefficient variance (GGT-CV), standard deviation (GGT-SD), and variability independent of the mean (GGT-VIM). Using the population-based Korean National Health Insurance Service-Health Screening Cohort, we followed 158,736 Korean adults over a median duration of 8.4 years. In multivariable Cox proportional hazard analysis, the risk of mortality, MI, and stroke showed a stepwise increase according to the quartiles of GGT-CV, GGT-SD or GGT-VIM. In the highest quartile of GGT-CV compared to the lowest quartile after adjusting for confounding variables including mean GGT, the hazard ratios (HRs) for incident MI, stroke, mortality, and CVD-related mortality were 1.19 (95% confidence interval (CI), 1.06-1.34; p < 0.001), 1.20 (95% CI, 1.10-1.32; p < 0.001), 1.41 (95% CI, 1.33-1.51; p < 0.001), and 1.52 (95% CI, 1.30-1.78; p < 0.001), respectively, which were similar or even higher compared with those associated with total cholesterol variability. This is the first study to demonstrate that high GGT variability is associated with increased risk of MI, stroke, all-cause mortality, and CVD-related mortality in the general population.
Project description:We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009-2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03-1.10) and 1.23 (1.20-1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.
Project description:Although liver enzymes, such as ?-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), have recently been suggested as risk factors for cardiovascular diseases (CVD), impact on mortality after myocardial infarction (MI) or ischemic stroke (IS) was not previously examined. Using a population-based, nationwide cohort database, we explored the implication of GGT and aminotransferases on the development of CVD and all-cause mortality during a median 9.1 years of follow-up. Among 16,624,006 Korean adults, both GGT and aminotransferases exhibited a positive relationship with MI, IS, and mortality in a multivariate adjusted model. ALT and AST showed U-shaped associations with mortality, whereas GGT showed a positive linear relationship with mortality. The risk of 1-year mortality after MI or IS was significantly higher in the highest quartile of GGT compared to the lowest quartile (HR, 1.46; 95% CI, 1.40-1.52). The implication of GGT on MI, IS, and mortality persisted regardless of traditional cardiovascular risk parameters. This study demonstrated the unique pattern of association of ALT, AST, and GGT with the development of CVD and all-cause mortality in the Korean population. In particular, GGT showed the most robust linear relationship with mortality before and after cardiovascular events independent of risk factors.
Project description:<h4>Purpose</h4>Investigate the relationship between pet ownership and cardiovascular (CV) outcomes.<h4>Methods</h4>We searched the PubMed, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases up to August 2018. Eligible publications examining the association between pet ownership and all-cause and CV mortality (primary outcomes) and risks of cardiovascular disease (CVD), myocardial infarction (MI), and stroke (secondary outcomes) were included. We used the Newcastle-Ottawa Scale to assess the quality of the articles.<h4>Results</h4>We included 12 studies, involving 488,986 participants (52.3% female, mean age 56.1 years), in our systematic review. The mean follow-up duration was 8.7 ± 6.3 years. Pet ownership had no association with adjusted all-cause mortality (odds ratio, OR = 1.01, 95% confidence interval, CI [0.94, 1.08], I2 = 76%), adjusted CV mortality (OR = 0.87, 95% CI [0.75, 1.00], I2 = 72%), or risk of cardiovascular disease (CVD) (OR = 0.87, 95% CI [0.72, 1.05], I2 = 73%), myocardial infarction (MI) (OR = 0.99, 95% CI [0.97, 1.01], I2 = 0%), or stroke (OR = 0.99, 95% CI [0.98, 1.01], I2 = 0%). However, subgroup analysis showed that pet ownership was associated with a lower adjusted CV mortality in the general population (OR = 0.93, 95% CI [0.86, 0.99], I2 = 27%) than in CVD patients. In patients with established CVD, pet ownership was associated with a lower adjusted CVD risk (OR = 0.71, 95% CI [0.60, 0.84], I2 = 0%).<h4>Conclusion</h4>Pet ownership is not associated with adjusted all-cause or CV mortality, or risk of CVD, MI, or stroke, but it is associated with a lower adjusted CV mortality in the general population and a lower CVD risk in patients with established CVD.
Project description:<h4>Aims</h4>A high visit-to-visit variability in cholesterol levels has been suggested to be an independent predictor of major adverse cardiovascular events in patients with coronary artery disease (CAD). Because whether this notion applies to general population is not known, we aimed to investigate the associations between total cholesterol (TC) variability and the risk of all-cause mortality, myocardial infarction (MI), and stroke.<h4>Methods and results</h4>We identified 3 656 648 subjects without a history of MI and stroke who underwent ≥3 health examinations from 2002 to 2007 in the Korean National Health Insurance System cohort. Total cholesterol variability was measured using the coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). There were 84 625 deaths (2.3%), 40 991 cases of MI (1.1%), and 42 861 cases of stroke (1.2%) during the median follow-up of 8.3 years. There was a linear association between higher TC variability and outcome measures. In the multivariable adjusted model, the hazard ratios and 95% confidence intervals comparing the highest vs. lowest quartiles of CV of TC were 1.26 (1.24-1.28) for all-cause mortality, 1.08 (1.05-1.11) for MI, and 1.11 (1.08-1.14) for stroke, which was independent of mean TC levels and the use of lipid-lowering agents. The results were consistent when modelling variability of TC using SD and VIM, and in various sensitivity analyses.<h4>Conclusion</h4>High variability in lipid levels is associated with adverse health-related outcomes. These findings suggest that lipid variability is an important risk factor in the general population.
Project description:<h4>Objective</h4>The prognostic value of long-term glycemic variability is incompletely understood. We evaluated the influence of visit-to-visit variability (VVV) of fasting blood glucose (FBG) on incident cardiovascular disease (CVD) and mortality.<h4>Research design and methods</h4>We conducted a prospective cohort analysis including 4,982 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) who attended the baseline, 24-month, and 48-month visits. VVV of FBG was defined as the SD or variability independent of the mean (VIM) across FBG measurements obtained at the three visits. Participants free of CVD during the first 48 months of the study were followed for incident CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) and all-cause mortality.<h4>Results</h4>Over a median follow-up of 5 years, there were 305 CVD events (189 CHD, 45 stroke, and 81 HF) and 154 deaths. The adjusted hazard ratio (HR) comparing participants in the highest versus lowest quartile of SD of FBG (?26.4 vs. <5.5 mg/dL) was 1.43 (95% CI 0.93-2.19) for CVD and 2.22 (95% CI 1.22-4.04) for all-cause mortality. HR for VIM was 1.17 (95% CI 0.84-1.62) for CVD and 1.89 (95% CI 1.21-2.93) for all-cause mortality. Among individuals without diabetes, the highest quartile of SD of FBG (HR 2.67 [95% CI 0.14-6.25]) or VIM (HR 2.50 [95% CI 1.40-4.46]) conferred a higher risk of death.<h4>Conclusions</h4>Greater VVV of FBG is associated with increased mortality risk. Our data highlight the importance of achieving normal and consistent glycemic levels for improving clinical outcomes.
Project description:We investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10-1.20), 1.22 (1.18-1.26), and 1.56 (1.53-1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.
Project description:<h4>Background</h4>Previous research regarding long-term glucose variability over several years which is an emerging indicator of glycemic control in diabetes showed several limitations. We investigated whether variability in long-term fasting plasma glucose (FG) can predict the development of stroke, myocardial infarction (MI), and all-cause mortality in patients with diabetes.<h4>Methods</h4>This is a retrospective cohort study using the data provided by the Korean National Health Insurance Corporation. A total of 624,237 Koreans???20 years old with diabetes who had undergone health examinations at least twice from 2005 to 2008 and simultaneously more than once from 2009 to 2010 (baseline) without previous histories of stroke or MI. As a parameter of variability of FG, variability independent of mean (VIM) was calculated using FG levels measured at least three times during the 5 years until the baseline. Study endpoints were incident stroke, MI, and all-cause mortality through December 31, 2017.<h4>Results</h4>During follow-up, 25,038 cases of stroke, 15,832 cases of MI, and 44,716 deaths were identified. As the quartile of FG VIM increased, the risk of clinical outcomes serially increased after adjustment for confounding factors including duration and medications of diabetes and the mean FG. Adjusted hazard ratios (95% confidence intervals) of FG VIM quartile 4 compared with quartile 1 were 1.20 (1.16-1.24), 1.20 (1.15-1.25), and 1.32 (1.29-1.36) for stroke, MI and all-cause mortality, respectively. The impact of FG variability was higher in the elderly and those with a longer duration of diabetes and lower FG levels.<h4>Conclusions</h4>In diabetes, long-term glucose variability showed a dose-response relationship with the risk of stroke, MI, and all-cause mortality in this nationwide observational study.
Project description:To examine associations of unhealthy lifestyle and genetics with risk of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke. We used data on 76,958 adults from the UK Biobank prospective cohort study. Favourable lifestyle included no overweight/obesity, not smoking, physical activity, not sedentary, healthy diet and adequate sleep. A Polygenic Risk Score (PRS) was derived using 300 CVD-related single nucleotide polymorphisms. Cox proportional hazard ratios (HR) were used to model effects of lifestyle and PRS on risk of CVD and all-cause mortality, stroke and MI. New CVD (<i>n</i> = 364) and all-cause (<i>n</i> = 2408) deaths, and stroke (<i>n</i> = 748) and MI (<i>n</i> = 1140) events were observed during a 7.8 year mean follow-up. An unfavourable lifestyle (0-1 healthy behaviours) was associated with higher risk of all-cause mortality (HR: 2.06; 95% CI: 1.73, 2.45), CVD mortality (HR: 2.48; 95% CI: 1.64, 3.76), MI (HR: 2.12; 95% CI: 1.65, 2.72) and stroke (HR:1.74; 95% CI: 1.25, 2.43) compared to a favourable lifestyle (≥4 healthy behaviours). PRS was associated with MI (HR: 1.35; 95% CI: 1.27, 1.43). There was evidence of a lifestyle-genetics interaction for stroke (<i>p</i> = 0.017). Unfavourable lifestyle behaviours predicted higher risk of all-cause mortality, CVD mortality, MI and stroke, independent of genetic risk.
Project description:<h4>Objective</h4>Patients submitted to carotid artery endarterectomy (CEA) have a long-term risk of major adverse cardiovascular events (MACE) of 6-9% at 2 years. Hematological parameters have been shown to have a predictive function in atherosclerotic diseases, namely the red blood cell distribution width-coefficient of variation (RDW-CV). This parameter has been associated with worse outcomes such as myocardial infarction (MI), stroke, and all-cause mortality. This study aims to evaluate the potential role of preoperative hematologic parameters such as RDW-CV in predicting perioperative and long-term cardiovascular adverse events and mortality in patients submitted to CEA.<h4>Methods</h4>From January 2012 to January 2019, 180 patients who underwent CEA with regional anesthesia in a tertiary care and referral center were selected from a prospective cohort database. Blood samples were collected preoperatively 2 weeks before admission, including a full blood count. The primary outcome included long-term MACE. Secondary outcomes included all-cause mortality, stroke, MI, acute heart failure, and major adverse limb events (MALE).<h4>Results</h4>At baseline, 27.2% of patients had increased RDW-CV. Increased RDW-CV was independently associated with baseline hemoglobin (adjusted odds ratio [aOR] 0.715, 95% CI 0.588-0.869, p = 0.001) and atrial fibrillation (aOR 4.028, 95% CI 1.037-15.639, p = 0.001). After a median follow-up of 50 months, log-rank univariate analysis of RDW-CV demonstrated a significant association between increased RDW-CV and long-term all-cause mortality (log-rank <0.001), MACE (log-rank <0.001), and MI (log-rank = 0.017). After multivariate Cox regression analysis, increased RDW-CV was associated with increased long-term mortality (adjusted hazard ratio [aHR] 2.455, 95% CI 1.231-4.894, p = 0.011) and MACE (aHR 2.047, 95% CI 1.202-3.487, p = 0.008). A decreased hemoglobin to platelet ratio (aHR 2.650e-8, 95% CI 9.049e-15 to 0.078, p = 0.019) was also associated with all-cause mortality.<h4>Conclusion</h4>RDW is a widely available and low-cost marker that independently predicts long-term mortality, MACE, and MI after CEA. This biomarker could prove useful in assessing which patients would likely benefit from CEA in the long term.
Project description:<h4>Objectives</h4>To examine associations of three diet quality indices and a polygenic risk score with incidence of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>UK Biobank, UK.<h4>Participants</h4>77 004 men and women (40-70 years) recruited between 2006 and 2010.<h4>Main outcome measures</h4>A polygenic risk score was created from 300 single nucleotide polymorphisms associated with CVD. Cox proportional HRs were used to estimate independent effects of diet quality and genetic risk on all-cause mortality, CVD mortality, MI and stroke risk. Dietary intake (Oxford WebQ) was used to calculate Recommended Food Score (RFS), Healthy Diet Indicator (HDI) and Mediterranean Diet Score (MDS).<h4>Results</h4>New all-cause (n=2409) and CVD (n=364) deaths and MI (n=1141) and stroke (n=748) events were identified during mean follow-ups of 7.9 and 7.8 years, respectively. The adjusted HR associated with one-point higher RFS for all-cause mortality was 0.96 (95% CI: 0.94 to 0.98), CVD mortality was 0.94 (95% CI: 0.90 to 0.98), MI was 0.97 (95% CI: 0.95 to 1.00) and stroke was 0.94 (95% CI: 0.91 to 0.98). The adjusted HR for all-cause mortality associated with one-point higher HDI and MDS was 0.97 (95% CI: 0.93 to 0.99) and 0.95 (95% CI: 0.91 to 0.98), respectively. The adjusted HR associated with one-point higher MDS for stroke was 0.93 (95% CI: 0.87 to 1.00). There was little evidence of associations between HDI and risk of CVD mortality, MI or stroke. There was evidence of an interaction between diet quality and genetic risk score for MI.<h4>Conclusion</h4>Higher diet quality predicted lower risk of all-cause mortality, independent of genetic risk. Higher RFS was also associated with lower risk of CVD mortality and MI. These findings demonstrate the benefit of following a healthy diet, regardless of genetic risk.