Impacts of early insulin treatment vs glimepiride in diabetic patients with background metformin therapy: A nationwide retrospective cohort study

Type 2 diabetes mellitus (T2DM) is a progressive disease. After metformin failure, the addition of insulin or sulfonylureas might increase the risk of hypoglycemia and cardiovascular (CV) morbidity. Here, the risk of all-cause mortality was compared between early insulin treatment and glimepiride use in T2DM patients with background metformin therapy.We conducted a 9-year retrospective cohort study from the population-based National Health Insurance Research Database in Taiwan. A total of 2054 patients with T2DM under insulin or glimepiride treatment were enrolled during 2004 to 2012. Overall event rates of all-cause mortality were compared between 1027 insulin users and 1027 matched glimepiride users.After the propensity score matching, the mortality rates were 72.5 and 4.42 per 1000 person-years for insulin users and glimepiride users. The adjusted hazard ratio of mortality was 14.47 (95% CI: 8.64–24.24; P value <.001) as insulin compared with glimepiride users. The insulin users had significantly higher risk of CV death (adjusted hazard ratio 7.95, 95% CI 1.65–38.3, P = .01) and noncardiovascular death (adjusted hazard ratio 14.9, 95% CI 8.4–26.3, P < .001).The nationwide study demonstrated that metformin plus insulin therapy was associated with higher risk of all-cause mortality.     

Association between body mass index and mortality in atrial fibrillation patients with and without diabetes mellitus: Insights from a multicenter registry study in China

Background and aimsThe aim of this study was to evaluate the association between body mass index (BMI) and mortality in atrial fibrillation (AF) patients with and without diabetes mellitus (DM).Methods and resultsA total of 1991 AF patients were enrolled and divided into two groups according to whether they have DM at recruitment. Baseline information was collected and a mean follow-up of 1 year was carried out. The primary outcome was defined as all-cause mortality with the secondary outcomes including cardiovascular mortality, stroke and major adverse events (MAEs). Univariable and multivariable Cox regression were performed to estimate the association between BMI and 1-year outcomes in AF patients with and without DM. 309 patients with AF (15.5%) had comorbid DM at baseline. Patients with DM were more likely to have cardiovascular comorbidities, receive relevant medications but carry worse 1-year outcomes. Multivariable Cox regressions indicated that elevated BMI was related with reduced risk of all-cause mortality, cardiovascular mortality and major adverse events. Compared to normal weight, overweight [HR (95% CI): 0.548 (0.405–0.741), p < 0.001] and obesity [HR (95% CI): 0.541 (0.326–0.898), p = 0.018] were significantly related with decreased all-cause mortality for the entire cohort. Remarkably reduced all-cause mortality in the overweight [HR (95% CI): 0.497 (0.347–0.711), p < 0.001] and obesity groups [HR (95% CI): 0.405 (0.205–0.800), p = 0.009] could also be detected in AF patients without DM, but not in those with DM.ConclusionElevated BMI was associated with reduced mortality in patients with AF. This association was modified by DM. The obesity paradox confined to AF patients without DM, but could not be generalized to those with DM.     

A Body Shape Index is positively associated with all-cause and cardiovascular disease mortality in the Chinese population with normal weight: A prospective cohort study

Background and aimA body shape index (ABSI) is a valuable predictor of mortality in the Western population, but similar evidence in the general Chinese population is limited. This study aims to evaluate the association between the ABSI and all-cause and cardiovascular disease (CVD) mortality in the Chinese population with normal weight.Methods and results9046 participants with normal BMI (18.5–24.9 kg/m²) from the China Hypertension Survey were enrolled. The baseline ABSI was calculated as waist circumference/(BMI^2/3height^1/2). Cox proportional hazards regression was performed to evaluate the association of the ABSI with all-cause and CVD mortality. Over an average follow-up of 5.4 years, 686 all-cause and 215 CVD deaths occurred. A 0.01-unit increment in the ABSI was associated with a 31% greater risk of all-cause mortality (hazard ratio [HR], 1.31; 95% CI: 1.12, 1.48) and CVD mortality (HR, 1.30; 95% CI: 1.08, 1.58). Compared with quartile 1 of the ABSI, the adjusted HRs of all-cause mortality for quartiles 2–4 were, respectively, 1.25 (95% CI: 0.98, 1.59), 1.28 (95% CI: 0.99, 1.67), and 1.54 (95% CI: 1.17, 2.03) (P_trend = 0.004), and those of CVD mortality for quartiles 2–4 were, respectively, 1.28 (95% CI: 0.88, 1.83), 1.42 (95% CI: 0.97, 2.08), and 1.45 (95% CI: 0.98, 2.170) (P_trend = 0.043). The dose–response analysis showed a linear positive association of the ABSI with all-cause (P_nonlinearity = 0.158) and CVD mortality (P_nonlinearity = 0.213).ConclusionThe ABSI was positively associated with all-cause and CVD mortality among the general Chinese population with normal BMI. The data suggest that the ABSI may be an effective tool for central fatness for mortality risk assessment.     

Five-year mortality trends associated with chronic pancreatitis in South Korea: A population based cohort study

BackgroundChronic pancreatitis (CP) is associated with all-cause and cancer-related mortality; however, the risk of mortality associated with alcoholic and non-alcoholic CP remains controversial. This study investigated whether CP increased the risk of 5-year all-cause and cancer-specific mortality compared to a control population.MethodsThis population-based study used data from a sample cohort of the National Health Insurance Service (NHIS) database in South Korea. CP was defined as disease code K86.0 (alcohol-induced CP) and K86.1 (other CP and non-alcoholic CP) from the tenth edition of the International Classification of Diseases.ResultsThe prevalence of chronic alcoholic pancreatitis increased from 0.01% in 2002 to 0.07% in 2015, and the prevalence of chronic non-alcoholic pancreatitis increased from 0.08% in 2002 to 0.50% in 2015. In the 2010 NHIS cohort (n = 826,909), CP was associated with an increased risk of 5-year all-cause mortality (hazard ratio [HR] = 1.25, 95% confidence interval [CI]: 1.25 to 1.66, P < 0.001). Additionally, non-alcoholic CP was associated with an increased risk of 5-year all-cause mortality (HR = 1.47, 95% CI: 1.27 to 1.71, P < 0.001); in contrast, alcohol-induced CP was not significantly associated with mortality risk (P = 0.569). Similar tendencies were observed for the 5-year cancer-related mortality risk.ConclusionsIn South Korea, the prevalence of alcoholic and non-alcoholic CP increased during 2002–2015. CP may be an independent risk factor for 5-year all-cause and cancer-related mortality. In this study, this association was more evident in patients with non-alcoholic CP.     

Metformin and risk of cancer among patients with type 2 diabetes mellitus: A systematic review and meta-analysis

AimWe carried out this meta-analysis on all published studies to estimate the overall cancer risk of the use of metformin in T2DM patients.MethodsWe searched the PubMed, Embase and CNKI databases for all articles within a range of published years from 2007 to 2019 on the association between the use of metformin and cancer risk in T2DM patients. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the association using a random-effect meta-analysis.ResultsFinally, 67 studies met the inclusion criteria for this study, with 10,695,875 T2DM patients and 145,108 cancer cases. Overall, For T2DM patients of ever vs. never metformin users, there was statistical evidence of significantly decreased cancer risk was found to be associated with ever metformin users (OR = 0.70, 95% CI = 0.65–0.76). Considering T2DM may be a specific and independent risk factor for various forms of cancer, due to its particular metabolic characteristics of glucose intolerance and hyperinsulinemia, we performed a comparison to estimate the effects of metformin on cancer risk with other anti-diabetes medications (ADMs), our results found significantly decreased cancer risk to be associated with the use of metformin (OR = 0.80, 95% CI = 0.73–0.87).ConclusionOur meta-analysis indicated that metformin may be a independent protective factor for cancer risk in T2DM patients.     

Safety and efficacy of anticoagulant monotherapy in atrial fibrillation and stable coronary artery disease: A systematic review and meta-analysis

BackgroundAdjunctive use of oral anticoagulant (OAC) and antiplatelet therapy (APT) in patients with stable coronary artery disease (CAD) and nonvalvular atrial fibrillation (AF) is a challenge of daily practice.MethodsA comprehensive literature search of databases was performed to identify studies comparing the safety and efficacy of OAC monotherapy and combined therapy (OAC plus single (S) APT). Events including major adverse cardiovascular events (MACE), all-cause mortality, stroke and major bleeding were analyzed.ResultsSeven articles comprising 11,070 subjects were identified. Combined therapy was associated with a significantly higher risk of major bleeding (pooled hazard ratio (HR) of 1.62, 95% CI 1.40–1.86, p=<0.0001) compared to the OAC monotherapy. There was no significant difference between the two comparison arms in terms of MACE (HR 1.14; 95% CI 0.97–1.34, p = 0.11), stroke (HR 1.05; 95% CI 0.77–1.43, p = 0.78) and all-cause mortality (HR 1.15; 95% CI 0.94–1.40, p = 0.16). Stratified analysis by inclusion of only patients with coronary stents attenuated the safety effect of monotherapy. Subgroup analysis based on the study design, type of OAC, major bleeding criteria and APT revealed findings consistent with the pooled HR. The combined therapy group had a 19% and 38% higher risk of MACE in studies with a history of MI (p = 0.03) and with the use of rivaroxaban (p = 0.02), respectively.ConclusionOAC monotherapy might have a lower incidence of major bleeding events with no higher overall risk of MACE, ischemic stroke and all-cause mortality compared to the combined therapy group.     

Clinical Predictors of Mortality in Patients with Moderate to Severe Mitral Regurgitation

BackgroundMitral regurgitation is the most common form of valvular heart disease worldwide, however, there is an incomplete understanding of predictors of mortality in this population. This study sought to identify risk factors of mortality in a real-world population with mitral regurgitation.MethodsAll patients with moderate or severe mitral regurgitation were identified at a single center from January 1, 2016 to August 31, 2017. Multivariate regression was performed to evaluate variables independently associated with all-cause mortality.ResultsA total of 490 patients with moderate (76.3%) or severe (23.7%) mitral regurgitation due to primary (20.8%) or secondary (79.2%) etiology were identified. The mean age was 66.7 years; 50% were male. At a median follow-up of 3.1 years, the incidence of all-cause mortality was 30.1%, heart failure hospitalization 23.1%, and mitral valve intervention 11.6%. Of 117 variables, multivariate analysis demonstrated 5 that were independently predictive of mortality: baseline creatinine (hazard ratio [HR] 1.2; 95% CI, 1.0-1.3; P = .02), right atrial pressure by echocardiogram (HR 1.3; 95% CI, 1.07-1.55; P = .008), hemoglobin (HR 0.65; 95% CI, 0.52-0.83; P = .001), hospitalization for heart failure (HR 1.6; 95% CI, 1.1-2.4; P = .015), and mitral valve intervention (HR 0.40; 95% CI, 0.16-0.83; P = .049).ConclusionIn this retrospective, pragmatic analysis of patients with moderate or severe mitral regurgitation, admission for heart failure exacerbation, elevated right atrial pressure, renal dysfunction, anemia, and lack of mitral valve intervention were independently associated with increased risk of all-cause mortality. Whether these risk factors may better identify select patients who may benefit from more intensive monitoring or earlier intervention should be considered in future studies.     

Statin use and the risk of CVD events,stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis

AimsConsidering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention.Data synthesisThe MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69–0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65–0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70–0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63–0.85, P < 0.0001).ConclusionsStatin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes.Systematic review registrationPROSPERO CRD42021281132.     

Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality

BackgroundReduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.ObjectivesThis study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.MethodsA total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.ResultsAn increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.ConclusionsGenetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population.     

Associations of dietary protein intake with all-cause,cardiovascular disease,and cancer mortality: A systematic review and meta-analysis of cohort studies

Background and aimsThe relationships between dietary protein intake and risk of all-cause, cardiovascular disease (CVD), and cancer mortality are still unclear. We conducted a systematic review with meta-analysis of cohort studies to summarize the evidence.Methods and resultsWe searched PubMed and Web of Science for relevant studies through February 2020. The associations of total, animal, and plant proteins with all-cause, CVD, and cancer mortality were evaluated. Study-specific relative risks (RR) were pooled using the fixed effect model when no significant heterogeneity was detected; otherwise the random effect model was employed. Twelve cohort studies were eligible for the study. Increased total protein showed no clear association with risk of all-cause, CVD, and cancer mortality. In the stratified analysis by protein sources, higher plant protein intake was associated with a reduced risk of all-cause mortality (highest vs lowest intake: RR = 0.92; 95% CI: 0.88, 0.96; each 3% increment of intake: RR = 0.97; 95% CI: 0.94, 0.99), and may be associated with a reduced risk of CVD mortality (highest vs lowest intake: RR = 0.90; 95% CI: 0.80, 1.01; each 3% increment of intake: RR = 0.95; 95% CI: 0.91, 0.99). Moreover, higher intake of animal protein may be associated with an increased risk of CVD mortality (highest vs lowest intake: RR = 1.11; 95% CI: 1.01, 1.22; each 3% increment of intake: RR = 1.02; 95% CI: 0.98, 1.06).ConclusionThis study demonstrates that higher plant protein intake is associated with a reduced risk of all-cause and CVD-related mortality. Persons should be encouraged to increase their plant protein intake to potentially decrease their risk of death.     

Long-Term Outcomes of Left Main Coronary Artery Disease Treated With Drug-Eluting Stents vs Coronary Artery Bypass Grafting: A Meta-Analysis and Systematic Review

BackgroundCurrently, DES is a reasonable treatment option for LMCA disease but CABG continues to be first-line treatment. Multiple randomized clinical trials (RCTs) have compared outcomes between these two treatment modalities. Recently, these trials published their long-term results with conflicting findings.MethodsWe conducted a systematic review and meta-analysis of RCTs that compared DES vs CABG in patients with LMCA disease. We only included trials with follow up duration of at least 5 years. The primary outcome was all-cause mortality. Secondary outcomes included risk of cardiac death, myocardial infarction (MI), stroke and repeat revascularization.ResultsWe included a total of 4 RCTs. The median-weighted follow up period was 6.5 years. There was no significant difference between DES and CABG in all-cause mortality (Risk ratio (RR) 1.10; 95% confidence interval (CI) 0.92 to 1.31; p = 0.28), risk of cardiac death (RR of 1.08, 95% CI 0.84 to 1.38; p = 0.56), total MI (RR of 1.22, 95% CI 0.96 to 1.56; p = 0.11), and stroke (RR of 0.85, 95% CI 0.46 to 1.57; p = 0.60). The risk of repeat revascularization (RR of 1.75, 95% CI 1.50 to 2.03; p < 0.00001), and non-periprocedural MI (RR of 2.13, 95% CI 1.53 to 2.97; p < 0.00001) were significantly higher in the DES arm.ConclusionsDES has similar long-term outcomes compared to CABG in terms of all-cause mortality, cardiac death, total MI and stroke; but was associated with a higher risk of repeat revascularization, and non-periprocedural MI.     

Modification of the all-cause and cardiovascular disease related mortality risk with changes in the metabolic syndrome status: a population-based prospective cohort study in Taiwan

AimTo examine whether changes in metabolic syndrome (MetS) status over time are associated with risk of all-cause and cardiovascular disease related (CVD) mortality.MethodsThis prospective cohort study consisted of 544,749 individuals who participated in a self-funded comprehensive health surveillance program offered by Taiwan MJ Health Management Institution between 1998 and 2016. We included 236,216 adults who had at least two repeated MetS measures 5.9 (4.6) years apart and were followed up for mortality over 18.8 (5.2) years. Participants were classified according to the change in their MetS status as follows: MetS-free at both time points (n = 173,116), MetS-developed (n = 22,607), MetS-recovered (n = 13,616), and MetS-persistent (n = 26,877). Multivariable Cox proportional hazards model was used to determine the association between change in MetS status and risk of all-cause and CVD mortality.ResultsOver the 4,436,842 person-years follow-up period, 14,226 participants died, including 2671 (19%) of CVD-related causes. The crude CVD mortality rate per 1000 person-years in the study groups were MetS-free, 0.32; MetS-developed, 0.75; MetS-recovered, 1.22; and MetS-persistent, 2.00 (P < 0.001). Compared to the persistent MetS group, participants in the MetS-recovered group had a lower risk of all-cause (adjusted hazard ratio [aHR], 0.87; 95%CI, 0.82–0.92) and CVD mortality (aHR, 0.81; 95% confidence interval [CI], 0.71–0.93). Development of MetS increased the risk for all-cause (aHR, 1.11; 95%CI, 1.05–1.17) and CVD mortality (aHR, 1.22; 95%CI, 1.07–1.39), compared to the MetS-free group.ConclusionRecovery from MetS was significantly associated with a lower risk of all-cause and CVD mortality, whereas development of MetS was associated with increased risk.     

A Common NOS1AP Genetic Polymorphism,rs12567209 G>A,Is Associated With Sudden Cardiac Death in Patients With Chronic Heart Failure in the Chinese Han Population

BackgroundVariants in NOS1AP associated with cardiac repolarization and sudden cardiac death (SCD) in coronary artery disease have been reported. Whether they are related to mortality and QTc interval in chronic heart failure (CHF) has not been investigated.Methods and ResultsA total of 1,428 patients with CHF and 480 control subjects were genotyped for 6 SNPs of NOS1AP, and the genetic associations with mortality as well as QTc interval were analyzed. During a median follow-up period of 52 months, 467 patients (32.70%) died, of which deaths 169 (36.19%) were SCD. The A allele of rs12567209 was associated with greater risk of all-cause death and SCD (hazard ratio [HR] 1.381, 95% confidence interval [CI] 1.124–1.698 [P = .002], and HR 1.645, 95% CI 1.184–2.287 [P = .003], respectively). After adjusting for other risk factors, significant differences remained (HR 1.309, 95% CI 1.054–1.624 [P = .015], and HR 1.601, 95% CI 1.129–2.271 [P = .008]). The A allele was also associated with prolongation of QTc interval by 4.04 ms in the entire population (P = .026).ConclusionsThe A allele of rs12567209 in NOS1AP may serve as an independent predictor of all-cause death and SCD in patients with CHF, it is also associated with prolonged QTc interval in the Chinese Han population.     

Safety of coffee consumption after myocardial infarction: A systematic review and meta-analysis

Background and aimsThis systematic review aims to evaluate the impact of coffee consumption in patients with previous myocardial infarction (MI), in relation to all-cause and cardiovascular mortality, as well as other major cardiovascular events (MACE) such as stroke, heart failure, recurrent MI and sudden death.Methods and resultsMEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection, SciELO Citation Database, Current Contents Connect®, KCI Korean Journal Database, African Index Medicus, and LILACS were searched for longitudinal studies evaluating the impact of coffee consumption in patients with previous myocardial infarction. We performed a random-effects meta-analysis to estimate the pooled hazard ratios (HR) with 95% confidence intervals (CI). The statistical heterogeneity was measured by I². A dose–response analysis was also conducted.Six prospective cohort studies were included in the primary meta-analysis. Consumption of coffee was associated with lower risk of cardiovascular mortality (HR = 0.70; 95% CI 0.54–0.91, I² = 0%; 2 studies) and was not associated with an increased risk of all-cause mortality (HR = 0.85; 95% CI 0.63–1.13; I² = 50%; 3 studies), recurrent MI (HR = 0.99; 95% CI 0.80–1.22; I² = 0%; 3 studies), stroke (HR = 0.97; 95% CI 0.63–1.49; I² = 39%; 2 studies) and MACE (HR = 0.96; 95% CI 0.86–1.07; I² = 0%; 2 studies). A significant non-linear inverse dose–response association was found for coffee consumption and all-cause mortality.ConclusionsConsumption of coffee was not associated with an increased risk of all-cause mortality and cardiovascular events in patients with previous myocardial infarction.     

Gender differences in the impact of metabolic syndrome components on mortality in older people: A systematic review and meta-analysis

Background and aimsThe influence of metabolic syndrome (MetS) on mortality may be influenced by age- and gender-related changes affecting the impact of individual MetS components. We investigated gender differences in the association between MetS components and mortality in community-dwelling older adults.Methods and resultsProspective studies were identified through a systematic literature review up to June 2019. Random-effect meta-analyses were run to estimate the pooled relative risk (RR) and 95% confidence intervals (95% CI) of all-cause and cardiovascular (CV) mortality associated with the presence of MetS components (abdominal obesity, high triglycerides, low HDL cholesterol, high fasting glycemia, and high blood pressure) in older men and women. Meta-analyses considering all-cause (103,859 individuals, 48,830 men, 55,029 women; 10 studies) and CV mortality (94,965 individuals, 44,699 men, 50,266 women; 8 studies) did not reveal any significant association for abdominal obesity and high triglycerides in either gender. Low HDL was associated with increased all-cause (RR = 1.16, 95% CI: 1.02–1.32) and CV mortality (RR = 1.34, 95% CI: 1.03–1.74) among women, while weaker results were found for men. High fasting glycemia was associated with higher all-cause mortality in older women (RR = 1.35, 95% CI: 1.22–1.50) more than in older men (RR = 1.21, 95% CI: 1.13–1.30), and CV mortality only in the former (RR = 1.36, 95% CI: 1.04–1.78). Elevated blood pressure was associated with increased all-cause mortality (RR = 1.16, 95% CI: 1.03–1.32) and showed marginal significant results for CV death only among women.ConclusionsThe impact of MetS components on mortality in older people present some gender differences, with low HDL cholesterol, hyperglycemia, and elevated blood pressure being more strongly associated to all-cause and CV mortality in women.     

Associations of vitamin B6 turnover rate with the risk of cardiovascular and all-cause mortality in hypertensive adults

Background and aimThis study was to assess the association between vitamin B6 turnover rate and mortality in hypertensive adults.Methods and resultsVitamin B6 status including serum pyridoxal-5′-phosphate (PLP) levels, serum 4-pyridoxal acid (4-PA) levels, and vitamin B6 turnover rate (4-PA/PLP) were obtained from the 2005–2010 National Health and Nutrition Examination Survey (NHANES) dataset of hypertensive adults with follow-up through December 30, 2019. Using Cox proportional risk regression models, Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for PLP, 4-PA and 4-PA/PLP quartiles in relation to cardiovascular and all-cause mortality. A total of 5434 participants were included in this study (mean age, 58.48 years; 50.4% men), and the median 4-PA/PLP was 0.75. The median follow-up time was 11.0 years, with 375 and 1387 cardiovascular and all-cause deaths, respectively. In multivariate COX regression models, PLP was negatively associated with cardiovascular mortality (HR [95% CI] quartile 4 vs. 1: 0.66 [0.47–0.94], P_trend = 0.03) and 4-PA/PLP was positively associated with cardiovascular mortality (HR [95% CI] quartile 4 vs.1: 1.80 [1.21–2.67], P_trend = 0.01). Similarly, the higher the quartile of PLP, the lower the risk of all-cause mortality (HR [95% CI] quartile 4 vs. 1: 0.67 [0.56–0.80], P_trend < 0.01). The higher the quartile of 4-PA and 4-PA/PLP, the higher the risk of all-cause mortality (HR [95% CI] quartile 4 vs. 1: 1.22 [1.01–1.48], P_trend < 0.01; and 2.09 [1.71–2.55], P_trend < 0.01).ConclusionThe findings suggested that higher vitamin B6 turnover rate was associated with an increased risk of cardiovascular and all-cause mortality in hypertensive adults.     

Association of serum C-peptide with all-cause and cardiovascular disease mortality in ultrasound-defined nonalcoholic fatty liver disease

ObjectiveTo determine the prognostic value of C-peptide in long-term nonalcoholic fatty liver disease (NAFLD) mortality.MethodsA total of 4670 participants with NAFLD were enrolled in this study. Multivariable Cox regression models evaluated the links between C-peptide levels and all-cause and cardiovascular disease (CVD) mortality risk using adjusted hazard ratios (aHR). In addition, a two?piecewise Cox model with penalized splines was adapted to investigate the nonlinear relationships between C-peptide and mortality.ResultsAfter a mean follow?up period of 20 years, 1714 deaths from all causes were recorded. In an adjusted Cox regression analysis, using the low C-peptide group as the reference (quartile 1), higher C-peptide (quartile 4) was notably associated with increased all-cause mortality (aHR =1.39; 95% CI: 1.18–1.65) and CVD death (aHR = 1.97; 95% CI: 1.41–2.76). Spline analyses demonstrated that the association between C-peptide levels and all-cause mortality was U-shaped, with a threshold value of 0.41 nmol/L. Below the threshold, every one-unit increment in C-peptide had a 70% reduced risk of all-cause death (aHR = 0.30, 95% CI: 0.1–0.7). Above the threshold, the C-peptide levels were associated with a higher probability of all-cause death (aHR = 1. 3, 95% CI:1.2–1.4).ConclusionsIn the US NAFLD population defined by ultrasound, a U-shaped association was detected between baseline serum C-peptide level and all-cause mortality.     

Effect of metformin on all-cause mortality and major adverse cardiovascular events: An updated meta-analysis of randomized controlled trials

AimsThe Italian Society of Diabetology and the Italian Association of Clinical Diabetologists are developing new guidelines for drug treatment of type 2 diabetes. The effects of anti-hyperglycaemic drugs on all-cause mortality and major adverse cardiovascular events (MACEs) were included among the critical clinical outcomes. We have therefore carried out an updated meta-analysis on the effects of metformin on these outcomes.Data synthesisA MEDLINE and EMBASE search was performed to identify all randomized controlled trials (RCTs) with duration ≥52 weeks (published up to August 2020), in which metformin was compared with either placebo/no therapy or active comparators. MACEs (restricted for RCT reporting MACEs within their study endpoints) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified endpoints) were considered as the primary endpoints. Mantel-Haenszel odds ratio (MH–OR) with 95% confidence interval was calculated for all endpoints considered. Metformin was associated with a nonsignificant reduction of all-cause mortality (n = 13 RCTs; MH–OR 0.80 [95% CI 0.60, 1.07]). However, this association became statistically significant after excluding RCTs comparing metformin with sulfonylureas, SGLT-2 inhibitors or GLP-1 analogues (MH–OR 0.71 [0.51, 0.99]). Metformin was associated with a lower risk of MACEs compared with comparator treatments (n = 2 RCTs; MH–OR 0.52 [0.37, 0.73]), p < 0.001. Similar results were obtained in a post-hoc analysis including all RCTs fulfilling criteria for inclusion in the analysis (MH–OR: 0.57 [0.42, 0.76]).ConclusionsThis updated meta-analysis suggests that metfomin is significantly associated with lower risk of MACEs and tendentially lower all-cause mortality compared to placebo or other anti-hyperglycaemic drugs.     

Elevated serum uric acid and risk of cardiovascular or all-cause mortality in maintenance hemodialysis patients: A meta-analysis

Background and aimsStudies have shown inconsistent results about the association between serum uric acid (SUA) levels and mortality in hemodialysis patients. We performed this meta-analysis to determine whether higher SUA values comprised a risk factor of cardiovascular or all-cause mortality in maintenance hemodialysis patients.Methods and resultsPubmed, Embase and the Cochrane library were searched up to August 31, 2020 for the longitudinal studies that investigated the association between the elevated SUA and cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. Pooled adjusted hazard ratios (HR) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. We included 10 studies with an overall sample of 264,571 patients with hemodialysis in this meta-analysis. Patients with the highest SUA were associated with a decreased risk of cardiovascular mortality (HR = 0.72, 95% CI 0.59–0.87) compared with patients with the lowest SUA after adjustment for potential confounders in a random effects model. Moreover, for each increase of 1 mg/dl of SUA, the overall risks of all-cause and cardiovascular mortality decreased by 6% and 9%, respectively (HR = 0.94, 95% CI 0.90–0.99; HR = 0.91, 95% CI 0.89–0.94).ConclusionElevated SUA levels are strongly and independently associated with lower risk of cardiovascular mortality in maintenance hemodialysis patients. More designed studies, especially randomized controlled trials, should be conducted to determine whether high SUA levels is an independent risk factor of all-cause mortality in hemodialysis patients.