Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: A meta-analysis of prospective studies

Objective

Serum uric acid (SUA) levels have been used to predict cardiovascular and all-cause mortality event, but the data have yielded conflicting results. We investigated whether SUA was an independent predictor for cardiovascular or all-cause mortality with prospective studies by meta-analysis.

Methods

Pubmed and Embase were searched without language restrictions for publications available till April 2013. Only prospective studies on cardiovascular or all-cause mortality related to SUA levels were included. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated separately for the highest vs. lowest category or the lowest vs. middle category.

Results

For the highest SUA, eleven studies with 172,123 participants were identified and analyzed. Elevated SUA increased risk of all-cause mortality (RR 1.24; 95% CI 1.09–1.42) and cardiovascular mortality (RR 1.37; 95% CI 1.19–1.57). Subgroup analyses showed that elevated SUA significantly increase the risk of all-cause mortality among men (RR 1.23; 95% CI 1.08–1.42), but not in women (RR 1.05; 95% CI 0.79–1.39). Risk of cardiovascular mortality appeared to be more pronounced among women (RR 1.35; 95% CI 1.06–1.72). The association between extremely low SUA and mortality was reported in three studies; we did not perform a pooled analysis because of high degree of heterogeneity in these studies.

Conclusions

Baseline SUA level is an independent predictor for future cardiovascular mortality. Elevated SUA appears to significantly increase the risk of all-cause mortality in men, but not in women. Whether low SUA levels are predictors of mortality is still inconclusive.     

Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes.

BACKGROUND: Increased serum uric acid (SUA) levels are linked to obesity, dyslipidemia, diabetes and hypertension. Whether SUA carries a risk for coronary heart disease (CHD) and stroke remains uncertain. DESIGN: A prospective cohort study. METHODS: Of an original cohort of middle-aged workers who were examined in 1963 and followed-up for 23 years, 9125 men, free of CHD at entry, are included in this study. Subjects were divided into quintiles according to baseline SUA levels. Hazard ratios (HR) for all-cause, CHD, and stroke mortality were estimated in SUA quintiles, with the third serving as a referent. RESULTS: During follow-up, 2893 deaths were recorded, including 830 ascribed to CHD and 292 to stroke. The HR for all death [1.22, 95% confidence interval (CI) 1.09-1.37] and CHD (1.29, 95% CI 1.05-1.58) were increased in the upper SUA quintile. Fatal stroke showed a U-shaped relationship as both the upper (HR 1.48, 95% CI 1.02-2.17) and bottom (HR 1.43, 95% CI 0.99-2.08) quintiles were associated with a higher risk. Adjustment for confounders reduced the HR of the upper quintile for all outcomes, but did not attenuate the association of the bottom quintile with stroke (HR 1.52, 95% CI 1.04-2.23). When analysed separately by stroke type, the latter association seemed to be stronger for hemorrhagic (HR 3.27, 95% CI 1.14-9.33) than for ischemic stroke (HR 1.34, 95% CI 0.87-2.05). CONCLUSION: In addition to findings supporting increased mortality among hyperuricemic subjects, we identified an association between low SUA levels and fatal stroke, which deserves further investigation.     

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.     

Self-reported habitual snoring and risk of cardiovascular disease and all-cause mortality

Objective

Inconsistent findings have reported the association between self-reported habitual snoring and risk of cardiovascular disease (CVD) and all-cause mortality. We conducted a meta-analysis to investigate whether self-reported habitual snoring was an independent predictor for CVD and all-cause mortality using prospective observational studies.

Methods

Electronic literature databases (PubMed, Medline, Embase, Cochrane Library, Wanfang database, and China National Knowledge Infrastructure) were searched for publications prior to September 2013. Only prospective studies evaluating baseline habitual snoring and subsequent risk of CVD and all-cause mortality were selected. Pooled adjust hazard risk (HR) and corresponding 95% confidence intervals (CI) were calculated for categorical risk estimates.

Results

Eight studies with 65,037 subjects were analyzed. Pooled adjust HR was 1.26 (95% CI 0.98–1.62) for CVD, 1.15 (95% CI 1.05–1.27) for coronary heart disease (CHD), and 1.26 (95% CI 1.11–1.43) for stroke comparing habitual snoring to non-snorers. Pooled adjust HR was 0.98 (95% CI 0.78–1.23) for all-cause mortality in a random effect model comparing habitual snoring to non-snorers. Habitual snoring appeared to increase greater stroke risk among men (HR 1.54; 95% CI: 1.09–2.17) than those in women (HR 1.22; 95% CI: 1.05–1.41).

Conclusions

Self-reported habitual snoring is a mild but statistically significant risk factor for stroke and CHD, but not for CVD and all-cause mortality. However, whether the risk is attributable to obstructive sleep apnea syndrome or snoring alone remains controversial.     

Association of Depression and Cardiovascular Disease

BackgroundCardiovascular disease remains the leading worldwide cause of mortality. There has been increased awareness of the impact of psychological health on cardiovascular disease. In particular, major depression has been linked to increased all-cause mortality, development of cardiovascular disease, and worse outcomes in those with existing cardiovascular disease.MethodsWe conducted a meta-analysis assessing the incidence of cardiovascular disease and cardiovascular disease outcomes among those with major depressive disorder.ResultsAmong 26 studies of 1,957,621 individuals, depression was associated with increased risk of incident stroke (hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.00-1.28), myocardial infarction (HR 1.28; 95% CI, 1.14-1.45), congestive heart failure (HR 1.04; 95% CI, 1.00-1.09), or any cardiovascular disease (HR 1.16; 95% CI, 1.04-1.30). Depression was associated with increased risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63), and congestive heart failure mortality (HR 3.20; 95% CI, 1.29-7.94).ConclusionDepression has a significant negative impact on development of cardiovascular disease and on cardiovascular disease outcomes. Further efforts to understand and mitigate these impacts are prudent.     

Use of fish oil and mortality of patients with cardiometabolic multimorbidity: A prospective study of UK biobank

Background and aimsCardiometabolic multimorbidity (CMM) has risen as a global issue of public health, with an in-creasing prevalence and more severe clinical prognosis. This study aimed to estimate the association between use of fish oil and mortality among patients with CMM.Methods and ResultsIn this prospective study based on UK Biobank, participants with ≥2 of cardiometabolic diseases (CMDs, including coronary heart disease [CHD], diabetes, hypertension, and stroke in this study) at recruitment were included. Use of fish oil was derived from touchscreen questionnaires at baseline. All-cause and cardiovascular mortality were accessed via electronic health-related records. Kaplan–Meier curves and flexible parametric Royston-Parmar proportion-hazard models were fitted to assess the as-sociations of fish-oil use with all-cause, cardiovascular mortality, and related life expectancy alterations. Among 30 068 participants from UK Biobank (67.9% men; mean age 61.75 years), 5357 deaths were reported during 12.03 years of follow-up. For patients with CMM, use of fish oil was associated with a 17% lower risk of all-cause mortality (95% confidence interval [95% CI] 0.78–0.88, P < 0.001), and 19% lower risk of cardiovascular mortality (95% CI 0.72–0.90, P < 0.001) in multivariable-adjusted models. At 45 years old, using fish oil was associated with 1.66 years of life expectancy gained.ConclusionAmong patients with CMM, use of fish oil was associated with a significantly reduced risk of all-cause, cardiovascular mortality, and prolonged life expectancy.     

Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

AimsTo evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.Data synthesisPubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.ConclusionsDrinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.Registry and registry numberThe protocol of this systematic review was registered at Open Science Framework (https://osf.io/8uaf3, registered form: osf.io/xur76, registration DOI: 10.17605/OSF.IO/8UAF3).     

Comparison of glucagons like peptide-1 receptor agonists and dipeptidyl peptide-4 inhibitors regarding cardiovascular safety and mortality in type 2 diabetes mellitus: A network meta-analysis

AimThe effects of dipeptidyl peptide-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) on type 2 diabetes mellitus (T2DM) on cardiovascular events and all-cause mortality were compared.MethodsThe literature on DPP-4is and SGLT-2is treatment of T2DM was searched through Pubmed, Embase, and the web of science databases with the search deadline May 15, 2020. Network meta-analysis (NMA) was used to compare the effects of two types of inhibitors on cardiovascular events (major adverse cardiovascular events (MACE), nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular (CV) death) and all-cause mortality in T2DM patients.ResultsA total of 15 articles were screened, including 125,796 patients. Compared with DPP-4is, SGLT-2is can significantly reduce MACE [OR: 0.86 95% CI (0.78, 0.92)], CV death [OR: 0.85 95% CI (0.71, 1.01)], nonfatal MI [OR: 0.84 95%CI (0.74, 0.95)] and all-cause mortality [OR: 0.78 95% CI (0.69, 0.89)]. For nonfatal stroke, DPP-4is and SGLT-2is have no statistically significant difference [OR: 0.99 95% CI (0.91, 1.07)].ConclusionThese data indicate that SGLT-2is is more beneficial to MACE and all-cause mortality in T2DM patients than DPP-4is.     

Low short-term and long-term cardiovascular and all-cause mortality in absence of coronary artery calcium: A 22-year follow-up observational study from large cohort

ObjectivesWe sought to evaluate the gender-specific predictive value of coronary artery calcium (CAC) score on all-cause mortality and cardiovascular disease (CVD) mortality in individuals with and without diabetes mellitus (DM).BackgroundCAC score is a robust predictor of CVD and all-cause mortality during long-term follow-up in large cohorts in adults with DM. However, less is known about its sex-specific impact on all-cause mortality in DM.MethodsWe evaluated 25,563 asymptomatic participants with no known history of coronary artery disease (CAD) who underwent clinically indicated CAC. 1999 (7.8%) individuals had diabetes. CAC was characterized as an Agatston score of 0, 1–99, 100–300, and ?300. We evaluated the association between CAC and all-cause mortality and CVD mortality.ResultsOverall, 1345 individuals died (5.3%) from all causes during a mean follow-up of 14.7 ± 3.8 years. CAC score was 0 in 57.5% females and 34.4% of males without DM, while 36.6% females and 20.3% males with DM had CAC-0. The frequency of CAC ? 300 was 18% and 36% in females and males with DM, respectively. CAC score of zero was associated with low all-cause mortality event rate in females and males with diabetes (1.7 and 2.5 events per 1000 person-years, respectively). Cardiovascular mortality per 1000 person years was ?1 in females and males with CAC score of 0 irrespective of their diabetes. Adjusted multivariable analysis, compared to CAC-0, HR for all-cause mortality associated with CAC 1–99, 100–299 and ?300 were 1.74(95% CI 0.65, 4.63, P-0.20), 5.54(95% CI 2.16, 14.22, P ? 0.001) and 5.75(95% CI 2.30, 14.37, P ? 0.001) in females with DM respectively; in males with DM HR associated with CAC 1–99, 100–299 and ?300 were 1.87(95% CI 0.95, 3.66, P-0.06), 2.15(95% CI 1.05, 4.38, P-0.035) and 2.60(95% CI 1.34, 5.0, P-0.004), respectively.ConclusionPresence of subclinical atherosclerosis varies among individuals with DM. The absence of CAC was associated with very low cardiovascular as well as all-cause mortality events in all subgroups during long term follow-up.     

Serum uric acid level and all-cause and cardiovascular mortality in Chinese elderly: A community-based cohort study in Shanghai

Background and aimsThe association between serum uric acid (SUA) and the all-cause and cardiovascular diseases (CVD) mortality remains controversial, but few studies based on the community population in Shanghai have been reported. We aimed to evaluate the association of SUA level with all-cause and CVD mortality in Chinese elderly based on a community-based cohort study in Shanghai of China.Methods and resultsA total of 12,071 eligible participants were included, with a cumulative follow-up period of 46,063.65 person-years and a median of 4.67 years. The time-dependent Cox regression model indicated that when SUA level was classified into quartile groups, no significant association was observed between SUA level and all-cause death in both men and women and between SUA level and CVD mortality in men. However, the HR (95%CI) between SUA groups and CVD death in women was 3.75 (1.49–9.43) for quartile 1, 3.66 (1.53–8.76) for quartile 2, and 2.98 (1.33–6.69) for quartile 4, respectively, when compared with the quartile 3 SUA level. A significant non-linear association was observed between SUA level and CVD death in elderly women. An increased risk of CVD death was observed among women with SUA level less than 4.30 mg/dL at the baseline, and a lower risk, among women with SUA level of 4.30–4.72 mg/dL at the baseline.ConclusionThe non-linear association between SUA level and CVD mortality in elderly women suggests a potential benefit of controlling SUA level at4.30–4.72 mg/dL in elderly Chinese women.     

Mortality in diabetes compared with previous cardiovascular disease: A gender-specific meta-analysis

AimsDiabetes has been described as a cardiovascular disease (CVD) risk equivalent. There is evidence, however, that its impact may differ between women and men. For this reason, our study aimed to obtain gender-specific hazard ratios (HRs) comparing diabetes and CVD patients in terms of all-cause, CVD and coronary heart disease (CHD) mortality.MethodsIndividuals with diabetes (without CVD) and those with CVD (without diabetes) were examined through a systematic review of articles that provided gender-specific HRs for mortality. Searches included Medline, Embase and the Cochrane Library database (from January 1998 to December 2009) and exploded MeSH headings [cardiovascular diseases, risk, epidemiologic studies, case-control studies, cohort studies, mortality, outcome assessment (health care), sex factors, survival analysis and diabetes mellitus, type 2]. Two observers selected and reviewed the studies and hierarchical Bayesian random-effects models were used to combine HRs, thereby accommodating any between-study differences through inclusion of a between-study variance in HRs.ResultsOut of 5425 studies, nine were relevant (0.17%). CVD and CHD mortality in men was lower for diabetes alone (CVD mortality HR: 0.82, 95% CrI: 0.69–0.98; CHD mortality HR: 0.73, 95% CrI: 0.65–0.83). In contrast, rates appeared to be higher in women with diabetes alone (CVD mortality HR: 1.29, 95% CrI: 0.79–2.26; CHD mortality HR: 1.28, 95% CrI: 0.75–2.22), although wide credible intervals precluded any definitive conclusions. All-cause mortality in men was similar for diabetes and previous CVD (HR: 1.02, 95% CrI: 0.93–1.12) whereas, among women, it was at least as high and possibly higher for diabetes alone (HR: 1.25, 95% CrI: 0.89–1.76).ConclusionCompared with previous CVD, diabetes alone leads to lower CVD and CHD mortality risk in men, and similar all-cause mortality. In contrast, although further studies are needed, it is possible that diabetes leads to higher CVD, CHD and all-cause mortality in women.     

Effects of pioglitazone on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

AimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. After identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, the experts decided to perform a systematic review and meta-analysis on the effect of pioglitazone with this respect.Data synthesisA MEDLINE database search was performed to identify RCTs, up to June 1st, 2021, with duration≥52 weeks, in which pioglitazone was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH–OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered.Eight RCTs were included in the analysis for MACEs and HF (5048 and 5117 patients in the pioglitazone and control group, respectively), and 24 in that for all-cause mortality (10,682 and 9674 patients). Pioglitazone neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH–OR: 0.90, 95% CI 0.78–1.03, 0.91, 95% CI 0.77, 1.09, and 1.16, 95% CI 0.73, 1.83, respectively). Pioglitazone was associated with a significant reduction of MACE in patients with prior cardiovascular events (MH–OR 0.84, 95% CI 0.72–0.99).ConclusionsThis meta-analysis showed no significant effects of pioglitazone on incident MACE, all-cause mortality, and HHF.     

Association of preexisting hypertension with the morality in patients with systolic heart failure in Taiwan: The TSOC-HFrEF registry

PurposeTo investigate the association of preexisting hypertension at admission with the mortality in patients with systolic heart failure (HF).MethodWe prospectively investigated the association of preexisting hypertension with the mortality among 1351 patients with HF in Taiwan during an average 12 months (range: 8 months–18 months) follow-up period. A multivariate cox regression analysis for the overall cohort and a subgroup analysis by age were performed.ResultsAfter adjustment for all potential risk factors, the associations of preexisting hypertension with cardiovascular mortality were significantly reduced in the overall cohort and those aged less than 65 years (hazard ratios (HR): 0.53, 95% confidence intervals (CI): 0.33–0.84, and 0.28, 95% CI: 0.11–0.67, respectively). However, the associations with all-cause mortality were not significantly different in these two groups (HR: 0.77, 95% CI: 0.54–1.09, and 0.59, 95% CI: 0.32–1.07, respectively). Furthermore, the associations were all nonsignificant in the patients aged older than 65 years.ConclusionPreexisting hypertension have an inverse association with cardiovascular mortality in the Asian patients with systolic HF, particularly for those with younger ages.     

Elevated depressive symptoms and risk of all-cause and cardiovascular mortality among adults with and without diabetes: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study

AimsTo examine the association of elevated depressive symptoms with all-cause and cardiovascular disease (CVD) mortality and determine whether these associations differ for those with and without diabetes.MethodsWe included 22,807 black and white men and women aged 45–98 years at baseline (2003–2007) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Elevated depressive symptoms were defined as a score ≥ 4 on the 4-item Centers for Epidemiologic Studies of Depression Scale. Participants were classified as having diabetes, prediabetes, or no prediabetes/diabetes based on glucose levels and diabetes medication use. All-cause mortality events were available through 2018 and adjudicated CVD mortality events were available through 2015.ResultsDuring follow-up, there were 5383 all-cause deaths, of which 1585 were adjudicated CVD deaths. The mean survival time was lower for participants with elevated depressive symptoms than those without elevated depressive symptoms for those with diabetes, prediabetes, and no prediabetes/diabetes. In multivariable adjusted models, elevated depressive symptoms increased the risk of all-cause mortality for those with diabetes (HR = 1.15; 95% CI = 1.00–1.32), prediabetes (HR = 1.56; 95% CI = 1.28–1.91), and neither prediabetes/diabetes (HR = 1.34; 95% CI = 1.19–1.50) (p for interaction = 0.0342). Findings were similar for CVD mortality.ConclusionElevated depressive symptoms increased the risk of all-cause and CVD mortality among individuals with and without diabetes, with a stronger magnitude of association observed among those with prediabetes. This underscores the need for assessing depressive symptoms across the glycemic spectrum, including those with prediabetes.     

The influence of sex on cardiovascular outcomes associated with diabetes among older black and white adults

AimsIt is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults.MethodsWe analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged ≥ 65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses.ResultsOver a median follow-up of 12.5 years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95% CI, 1.70–3.40]) than black men (1.39 [0.83–2.34]); this finding did not reach statistical significance (P for interaction = 0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82–3.26]) vs. (1.44 [0.97–2.12]), P for interaction = 0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P = 0.07).ConclusionsOverall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study.     

A case-cohort study of the association between adiponectin and mortality in EPIC–Heidelberg: NT-proBNP may explain the adiponectin paradox

Background and aimsNT-proBNP has been hypothesized as a possible explanation for the paradoxical association between adiponectin and cardiovascular and all-cause mortality. We examined the heterogeneities by NT-proBNP, sex, BMI, smoking status, hypertension and diabetes status in the association between adiponectin and cardiovascular disease risk and mortality.Methods and resultsWe used a case-cohort design nested within the EPIC-Heidelberg cohort, including 1387 incident cases of myocardial infarction or stroke, 582 deaths from cardiovascular causes and 2352 total deaths. We estimated hazard ratios for the association between 1SD increase in log-transformed total adiponectin levels and cardiovascular disease risk, cardiovascular mortality and mortality using Prentice-weighted Cox-proportional hazard models and assessed heterogeneity of the associations across strata of covariates. Overall, adiponectin was significantly associated with all-cause mortality [HR = 1.09, 95% CI: 1.03–1.16, p = 0.004]. The association with cardiovascular mortality did not reach statistical significance [1.10 (0.99–1.37), p = 0.073]. There was significant heterogeneity by NT-proBNP in the association between total adiponectin and all-cause mortality (phet = 0.019) such that significant increase in hazards of mortality were restricted to participants in the highest tertile of NT-proBNP. Among these participants, adiponectin showed a dose-response relationship with total mortality such that; compared to participants in the lowest quintile, those in the third, fourth and fifth were at 1.22 (0.87–1.70), 1.50 (1.07–2.11), and 1.59 (1.15–2.21) higher hazards of mortality respectively.ConclusionsSignificant association between adiponectin and mortality was only observed in the context of high NT-proBNP. Our findings provide further support for hypothesis that NT-proBNP may explain the adiponectin paradox.     

Effects of insulin on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

AimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin with this respect.Data synthesisA MEDLINE database search was performed to identify all RCTs, up to June 1st, 2021, with duration≥52 weeks, in which insulin was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered.Six RCTs (enrolling 8091 patients and 10,139 in the insulin and control group, respectively) were included in the analysis for MACEs and HF, and 18 in that for all-cause mortality (9760 and 11,694 patients in the insulin and control group, respectively). Treatment with insulin neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH-OR: 1.09, 95% CI 0.97–1.23; 0.99, 95% CI 0.91, 1.08; and 0.90, 95% CI 0.78, 1.04, respectively).ConclusionsThis meta-analysis showed no significant effects of insulin on incident MACE, all-cause mortality, and HHF.     

Impaired glucose tolerance predicts all-cause mortality among older men at high risk for cardiovascular disease in China

AimsTo investigate the potential association between impaired glucose tolerance (IGT) and all-cause mortality among older men at high risk for cardiovascular disease (CVD) in China.MethodsIn this prospective observational study, 460 older men aged ≥60 years were determined to have either IGT or normal glucose tolerance (NGT) based on an oral glucose tolerance test conducted between May 2005 and May 2007. IGT and NGT were diagnosed according to the 1999 WHO diagnostic criteria. All subjects were followed until March 2017. The primary outcome studied was all-cause mortality. Multivariate Cox models were used to estimate relative risk for all-cause mortality.ResultsDuring a mean follow-up of 11.2 years, forty-three (21.4%) subjects in the IGT group and twenty-nine (11.2%) subjects in the NGT group died (HR 2.05, 95% CI 1.28–3.28, P = 0.003). Multivariate Cox proportional-hazards analysis demonstated that IGT was significantly associated with increased risk for all-cause mortality, composite cardiovascular outcome, nonfatal stroke and heart failure after adjusting for potential confounding factors. Logistic regression analysis showed that IGT at baseline (P < 0.05) rather than incident type 2 diabetes was a risk factor of all-cause mortality.ConclusionsIGT was significantly associated with all-cause mortality in older Chinese men at high risk for CVD.     

Associations between calf,thigh, and arm circumference and cardiovascular and all-cause mortality in NHANES 1999–2004

Background and aimsPrior studies have described an association between calf circumference and cardiovascular disorders. We evaluated the associations between calf, thigh, and arm circumference and cardiovascular and all-cause mortality.Methods and resultsWe performed a retrospective cohort study of 11,871 patients in the 1999–2004 National Health and Nutrition Examination Survey (NHANES) to determine the association between calf circumference and cardiovascular and all-cause mortality using univariate and multivariate Cox proportional hazards. We additionally examined the association between thigh and arm circumference and mortality. In the multivariable Cox regression for the female stratum, each centimeter increase in calf circumference was associated with a hazard ratio of 0.88 (95% CI 0.84–0.92), and a hazard ratio of 0.90 (95% CI 0.85–0.95) for cardiovascular death. In the model with males, the hazard ratio for higher calf circumference was 0.92 (95% CI 0.88–0.96) for all-cause mortality and 0.94 (95% CI 0.89–0.99) for cardiovascular death. There was a statistically significant association between higher thigh circumference and lower risk of all-cause and cardiovascular mortality. Arm circumference was not similarly associated with mortality in the multivariate model.ConclusionCalf and thigh circumference may provide important prognostic information regarding cardiovascular and all-cause mortality. Future prospective studies should examine the role of extremity circumference and cardiovascular events.     

Fresh fruit consumption,physical activity,and five-year risk of mortality among patients with type 2 diabetes: A prospective follow-up study

Background and aimsWe explored the associations among fruit consumption, physical activity, and their dose–response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients.Methods and resultsWe prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21–94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose–response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64–0.88), CVD mortality (HR 0.69, 0.51–0.94) and stroke mortality (HR 0.57, 0.36–0.89), but not with heart disease mortality (HR 0.93, 0.56–1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37–0.53) for all-cause mortality, 0.46 (0.33–0.64) for CVD mortality, 0.46 (0.29–0.74) for stroke mortality and 0.51 (0.29–0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease.ConclusionsFruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.