Advanced glycation end products via skin autofluorescence as a new biomarker for major adverse cardiovascular events: A meta-analysis of prospective studies

AimsThis meta-analysis aimed to systematically evaluate the prospective association between advanced glycation end products (AGEs) and major adverse cardiovascular events (MACE).Data synthesisProspective studies that reported the association of AGEs (measured by skin autofluorescence) with MACE were searched in PubMed and EMBASE from inception up to July 2021. Multivariable-adjusted hazard ratios (HRs) and their respective 95% confidence intervals (CIs) reflecting the risk of MACE associated with AGEs were determined using random-effects meta-analysis. Fourteen articles with sixteen items involving 79,389 participants were included. A significant association was found between AGEs and MACE (pooled HR: 1.54, 95% CI: 1.31–1.81, I² = 68%). Moreover, AGEs were associated with a significant increase in fatal cardiovascular disease (CVD) (HR: 1.88, 95% CI: 1.30–2.70) and nonfatal CVD (HR: 1.40, 95% CI: 1.12–1.74). The association between AGEs and MACE was also significant in patients with diabetes (HR: 1.88, 95% CI: 1.31–2.69) and kidney disease (HR: 1.50, 95% CI: 1.16–1.94).ConclusionsThis meta-analysis indicates that higher levels of AGEs measured by skin autofluorescence are significantly correlated with a higher pooled risk of MACE, and AGEs are closely related to both nonfatal and fatal cardiovascular events. AGEs are a valuable biomarker for predicting the occurrence of MACE.The PROSPERO registration numberCRD42021279714.     

Serum and dietary vitamin D and cardiovascular disease risk in elderly men: a prospective cohort study

Background and aimRecent research suggests that low vitamin D may be associated with cardiovascular disease (CVD).Methods and resultsWe prospectively evaluated the association of dietary plus supplemental vitamin D intake and serum 25(OH) vitamin D with CVD incidence in the Osteoporotic Fractures in Men (MrOS) Study. Vitamin D intake was measured using a food frequency questionnaire and self-reported supplemental intake in 3094 men (mean age 76.4 years). From a subset of this population, we measured 25(OH) vitamin D in 813 men. Median 25(OH) vitamin D was 25.3 ng/mL. During a median follow-up of 4.4 years, there were 472 CVD cases, including 371 from coronary heart disease (CHD) and 101 from cerebrovascular attack (CVA). In the 25(OH) vitamin D sub-cohort, there were 140 cases of CVD including 115 from CHD and 25 from CVA. We used a Cox proportional hazards regression to calculate hazard ratios (HR) for CVD by vitamin D quartile. After adjusting for age, season, and standard CVD risk factors, the lowest quartile of 25(OH) vitamin D (HR, 1.18; 95% CI, 0.69–2.03) and vitamin D intake (HR, 0.76; 95% CI, 0.56–1.04) were not significantly associated with CVD incidence, compared to the highest vitamin D quartiles. When 25(OH) vitamin D was further analyzed by sufficiency (≥30 ng/mL), insufficiency (≥15–29.9 ng/mL), and deficiency (<15 ng/mL), vitamin D deficiency was not significantly associated with CVD incidence compared to sufficiency (HR 1.34; 95% CI 0.65–2.77).ConclusionVitamin D intake and serum 25(OH) vitamin D were not associated with CVD risk.     

Obesity and cardiovascular events in patients with established coronary disease.

AIMS: To explore the association between obesity and major adverse coronary events (MACE) in patients with established coronary artery disease (CAD). METHODS AND RESULTS: The Prevention of Events with Angiotensin Converting Enzyme-Inhibition (PEACE) Trial randomized 8290 patients with stable CAD and left ventricular (LV) ejection fraction (EF) (LVEF) > or =0.40 to trandolapril or placebo and followed them for a median of 4.8 years. In PEACE patients who were non-diabetic at baseline (5693 men and 1171 women), we used proportional hazards models to conduct a post hoc analysis to examine whether obesity, defined as a body mass index (BMI) > or =30 kg/m(2), is an independent risk factor for the composite endpoint of MACE, defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, or stroke. The analysis was conducted separately for men and women. The baseline prevalence of obesity was 28.5% in men and 28.9% in women. After adjusting for significant confounders, obesity was associated with MACE in men [hazard ratio (HR) = 1.28, 95% CI 1.13-1.46, P < 0.01], but not in women (HR = 0.96, 95% CI 0.70-1.31, P = 0.77). Further categorization of BMI showed a J-shaped association between BMI and MACE in the men, and no association in the women. CONCLUSION: In the presence of established CAD, obesity is associated with risk for MACE in men, but there is no support of an association in women. This finding requires further evaluation.     

Hemoglobin,Frailty, and Long-term Cardiovascular Events in Community-Dwelling Older Men Aged ≥ 70 Years

BackgroundAnemia is associated with increased risk of all-cause mortality in older populations. However, the relationship between hemoglobin and major adverse cardiovascular events (MACE), and whether this is modulated by frailty, is unclear.MethodsCHAMP (Concord Health and Ageing in Men Project) is a prospective study of community-dwelling men aged ≥ 70 years. The relationship between hemoglobin and 7-year MACE was analysed by means of Cox regression. The Youden index was used to determine the optimal hemoglobin cutoff point in predicting MACE. Frailty was assessed with the use of the Fried criteria.ResultsThe cohort comprised 1604 men (mean ± SD age 76.9 ± 5.5 years). Decreasing hemoglobin was associated with increased comorbidity, frailty, and MACE (P < 0.001), with 140 g/L the optimal cutoff point for predicting MACE. Hemoglobin, age, and frailty independently predicted MACE (all P < 0.001). Each 10 g/L decrement in hemoglobin level was associated with increased risk of MACE (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.06-1.20; P < 0.001), all-cause mortality (HR 1.20, 95% CI 1.12-1.29; P < 0.001), cardiovascular mortality (HR 1.07, 95% CI 1.01-1.14; P = 0.025), myocardial infarction (HR 1.17, 95% CI 1.09-1.25; P < 0.001), and heart failure (HR 1.17, 95% CI 1.09-1.25; P < 0.001). When stratified into hemoglobin quintiles, men in the lowest 2 quintiles (Hb 133-140 g/L and < 132g/L, respectively) were at increased risk of MACE, cardiovascular mortality, myocardial infarction, and heart failure (all P < 0.05). This relationship for MACE was independent from frailty status, with the test for interaction between frailty and hemoglobin not reaching significance (P = 0.24).ConclusionsLow hemoglobin was associated with increased MACE in community-dwelling older men independently from frailty. A hemoglobin cutoff point of 140 g/L, a level that is above contemporary definitions of anemia, predicted long-term MACE.     

Association of milk consumption with management and incidence of hypertension among South Korean adults: A prospective analysis of the health examinees study cohort

Background and aimsStudies have revealed a positive relationship between milk consumption and hypertension. However, few researchers have investigated the association between milk consumption and changes in blood pressure (BP) in South Korean adults. Therefore, we examined the association between milk intake and the management and risk of hypertension in South Korean adults.Methods and resultsParticipants were selected from the Health Examinees study. The definition of hypertension was based on the guidelines of the Korean Society of Hypertension. The participants were divided into three groups according to changes between baseline and follow-up BP data. Milk consumption was assessed using food frequency questionnaires. In both men and women, the higher milk consumption group had increased odds of trends of BP improvement (OR: 1.249, 95% CI: 1.043–1.496, p for trend: 0.2271 in men; OR: 1.147, 95% CI: 1.014–1.297, p for trend: 0.0293 in women) and decreased odds of trends of worsening (OR: 0.861, 95% CI: 0.756–0.980, p for trend: <0.0001 in men, OR: 0.866, 95% CI: 0.794–0.943, p for trend: 0.0010 in women) compared to those of the non-consumption group. In the prospective study, milk intake was inversely associated with hypertension risk (HR: 0.900, 95% CI: 0.811–0.999, p for trend: 0.0076 in men; HR: 0.879, 95% CI: 0.814–0.949, p for trend: 0.0002 in women).ConclusionIncreased intake of milk was inversely related to the risk of increased BP, with a decreased risk of hypertension events.     

Feasibility and Prognostic Value of Vasodilator Stress Perfusion CMR in Patients With Atrial Fibrillation

ObjectivesThe aim of this study was to assess the feasibility and prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients with atrial fibrillation (AF).BackgroundBecause most studies have excluded arrhythmic patients, the prognostic value of stress perfusion CMR in patients with AF is unknown.MethodsBetween 2008 and 2018, consecutive patients with suspected or stable chronic coronary artery disease and AF referred for vasodilator stress perfusion CMR were included and followed for the occurrence of major adverse cardiovascular event(s) (MACE), defined as cardiovascular death or nonfatal myocardial infarction. The diagnosis of AF was defined by 12-lead electrocardiography before and after CMR. Univariate and multivariate Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.ResultsOf 639 patients (mean age 72 ± 9 years, 77% men), 602 (94%) completed the CMR protocol, and 538 (89%) completed follow-up (median 5.1 years); 80 had MACE. Using Kaplan-Meier analysis, the presence of ischemia (hazard ratio [HR]: 7.56; 95% confidence interval [CI]: 4.86 to 11.80) or LGE (HR: 2.41; 95% CI: 1.55 to 3.74) was associated with the occurrence of MACE (p < 0.001 for both). In a multivariate Cox regression including clinical and CMR indexes, the presence of ischemia (HR: 5.98; 95% CI: 3.68 to 9.73) or LGE (HR: 2.61; 95% CI: 1.89 to 3.60) was an independent predictor of MACE (p < 0.001 for both).ConclusionsIn patients with AF, stress perfusion CMR is feasible and has good discriminative prognostic value to predict the occurrence of MACE.     

Sulfonylureas as second line therapy for type 2 diabetes among veterans: Results from a National Longitudinal Cohort Study

AimsTo assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone.Materials and MethodsThis was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes.ResultsSwitching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7–19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively).ConclusionsSwitching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy.     

Fasting insulin is a stronger cardiovascular risk factor in women than in men

Diabetes is a stronger risk factor for cardiovascular disease (CVD) in women than in men. It is not known whether there is also a sex difference in the association between hyperinsulinaemia, reflecting insulin resistance, and CVD. Fasting insulin was assessed with a specific assay in 6916 fasting, non-diabetic subjects of the PREVEND study without a prior history of CVD. Major Adverse Cardiovascular Events (MACE) (defined as CVD morbidity and CVD mortality) were prospectively recorded after the baseline survey. Cox-regression models were used to investigate the association of fasting insulin with subsequent development of MACE. Fasting insulin was 54 [38-77]pmol/l in women (age 48+/-12yrs) and 57 [40-88] pmol/l in men (age 49+/-13yrs). During follow-up for 7.5 [6.9-7.8]yrs, 98 cardiovascular events were recorded in 3626 women and 242 events in 3290 men. There was a significant (P<0.001) interaction between sex and fasting insulin for MACE, with the strongest association in women. In women, there was a logarithmic association for insulin with MACE, independent of age, alcohol consumption, and smoking (HR=1.50 [95% CI 1.17-1.91] per doubling of insulin, P=0.001). In men, for a similar multivariate model, there was a logarithmic association (HR=1.13 [95% CI [0.97-1.32] per doubling of insulin, P=0.1). Further adjustment for components of the insulin resistance syndrome weakened the association more in men than in women. With HOMA instead of insulin, results were essentially similar. In parallel with diabetes, fasting hyperinsulinaemia reflecting insulin resistance in non-diabetic subjects is associated with an increased risk for cardiovascular disease, which is more pronounced in women than in men.     

Dietary antioxidants, fruits, and vegetables and the risk of Barrett's esophagus

OBJECTIVE: The present study evaluated the associations among antioxidants, fruit and vegetable intake, and the risk of Barrett's esophagus (BE), a potential precursor to esophageal adenocarcinoma.
METHODS: We conducted a case–control study within the Kaiser Permanente Northern California population. Incident BE cases (N = 296) were matched to persons with gastroesophageal reflux disease (GERD) (GERD controls N = 308) and to population controls (N = 309). Nutrient intake was measured using a validated 110-item food frequency questionnaire. The antioxidant results were stratified by dietary versus total intake of antioxidants.
RESULTS: Comparing cases to population controls, dietary intake of vitamin C and beta-carotene were inversely associated with the risk of BE (4th vs 1st quartile, adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.26–0.90; OR 0.56, 95% CI 0.32–0.99, respectively), and the inverse association was strongest for vitamin E (OR 0.25, 95% CI 0.11–0.59). The inverse trends for antioxidant index (total and dietary) and fruit and vegetable intake were statistically significant, while most total intakes were not associated with reduced risk. The use of antioxidant supplements did not influence the risk of BE, and antioxidants and fruits and vegetables were inversely associated with a GERD diagnosis.
CONCLUSION: Dietary antioxidants, fruits, and vegetables are inversely associated with the risk of BE, while no association was observed for supplement intake. Our results suggest that fruits and vegetables themselves or associated undetected confounders may influence early events in the carcinogenesis of esophageal adenocarcinoma.     

Long-Term Outcomes in Women and Men Following Percutaneous Coronary Intervention

BackgroundStudies examining sex-related outcomes following percutaneous coronary intervention (PCI) have reported conflicting results.ObjectivesThe purpose of this study was to examine the sex-related risk of 5-year cardiovascular outcomes after PCI.MethodsThe authors pooled patient-level data from 21 randomized PCI trials and assessed the association between sex and major adverse cardiac events (MACE) (cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]) as well as its individual components at 5 years.ResultsAmong 32,877 patients, 9,141 (27.8%) were women. Women were older and had higher body mass index, more frequent hypertension and diabetes, and less frequent history of surgical or percutaneous revascularization compared with men. By angiographic core laboratory analysis, lesions in women had smaller reference vessel diameter and shorter lesion length. At 5 years, women had a higher unadjusted rate of MACE (18.9% vs. 17.7%; p = 0.003), all-cause death (10.4% vs. 8.7%; p = 0.0008), cardiac death (4.9% vs. 4.0%; p = 0.003) and ID-TLR (10.9% vs. 10.2%; p = 0.02) compared with men. By multivariable analysis, female sex was an independent predictor of MACE (hazard ratio [HR:]: 1.14; 95% confidence interval [CI:]: 1.01 to 1.30; p = 0.04) and ID-TLR (HR: 1.23; 95% CI: 1.05 to 1.44; p = 0.009) but not all-cause death (HR: 0.91; 95% CI: 0.75 to 1.09; p = 0.30) or cardiac death (HR: 0.97; 95% CI: 0.73 to 1.29; p = 0.85).ConclusionsIn the present large-scale, individual patient data pooled analysis of contemporary PCI trials, women had a higher risk of MACE and ID-TLR compared with men at 5 years following PCI.     

The Atrial fibrillation Better Care (ABC) pathway and cardiac complications in atrial fibrillation: a potential sex-based difference. The ATHERO-AF study

BackgroundAn integrated care approach is recommended to optimize management of patients with atrial fibrillation (AF). The impact of the Atrial fibrillation Better Care (ABC) pathway on major adverse cardiac events (MACE), which are the main causes of death in AF, has not been explored.Material and methodsWe investigated the association between ABC compliance and MACE incidence in 1157 (2690 patient-years) nonvalvular AF patients from the ATHERO-AF study. A subgroup analysis by sex and high cardiovascular risk patients as defined by a 2MACE score ≥3 was performed.ResultsOverall, 428 (37%) patients composed the ABC-compliant group. During a median follow up of 23 (IQR 12-37) months, 64 MACE occurred (2.38%/year). Kaplan Meier curve analysis showed a higher rate of MACE in ABC non-compliant group compared to the ABC-compliant (log-rank test p=0.006). The risk of MACE increased by the number of non-fulfilled ABC criteria. On multivariable Cox proportional hazard regression analysis, the ABC non-compliance was associated with an increased risk of MACE (Hazard ratio (HR) 2.244, 95% Confidence Interval (95%CI) 1.129-4.462). Men were more likely to have suboptimal anticoagulation control (group A), while uncontrolled symptoms were more frequent in women. The association between non-ABC and MACE was more evident in men than women (HR 3.647, 95%CI 1.294-10.277) and in patients with 2MACE score ≥3 (HR 1.728, 95%CI 1.209-2.472).ConclusionAn integrated care ABC approach is associated with a reduced risk of MACE in the AF population, especially in men and in patients at high risk of MACE.     

Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: A systematic review and meta-analysis of cardio-vascular outcome trials

Background and aimsType 2 diabetes confers a differential risk of cardiovascular (CV) disease according to the gender. Whether newly approved anti-diabetic drugs like sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) that have shown a significant reduction in the CV end-points in CV outcome trials (CVOTs) also have a differential impact gender-wise, is still not clearly known.MethodsWe systematically searched the medical database up to December 31, 2019 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs that explicitly reported the outcome of major adverse cardiac events (MACE). Subsequently, we pooled the hazard ratio (HR) of MACE in both sexes separately and meta-analyzed the result gender-wise.ResultsThe meta-analysis of three CVOTs conducted with SGLT-2Is (N = 34,322), demonstrated a significant reduction in MACE in men but not in women (Men - HR, 0.90; 95% CI, 0.83 to 0.97; P = 0.006; Women - HR, 0.88; 95% CI, 0.77 to 1.00; P = 0.06) compared to placebo. The meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 56,004) demonstrated a significant reduction in MACE in both sex (Men - HR, 0.88; 95% CI, 0.82 to 0.93; P < 0.0001; Women - HR, 0.88; 95% CI, 0.79 to 0.99; P = 0.03), against the placebo.ConclusionsThe reduction in MACE with SGLT-2Is appears to be significantly less in women with diabetes vs men, while GLP-1RAs confers a similar reduction in MACE, irrespective of the gender. Whether these results are related to inadequate statistical power (underrepresentation of women) in CVOT, or it reflects a true gender difference, still remains to be established.     

Alcohol consumption and risk of incident atrial fibrillation: A population-based cohort study

AimsAtrial fibrillation (AF) is a common tachyarrhythmia. High alcohol consumption is associated with increased AF risk. It remains unclear whether lower levels of alcohol consumption are also associated with AF risk, and whether the association differs between men and women. In this study, we investigated the association between low to moderate levels of alcohol consumption and AF risk in men and women.MethodsWe performed a population-based cohort study of 109,230 health examination participants in northern Sweden. Data regarding alcohol intake were obtained using a questionnaire administered at the health examination. Incident AF cases were identified from the Swedish National Patient Registry.ResultsAF was diagnosed in 5,230 individuals during a total follow-up of 1,484,547 person-years. Among men, AF risk increased over quartiles of weekly alcohol consumption (P for trend 0.001). Men with alcohol consumption in the highest quartile (≥4.83 standard drinks [each drink containing 12 gs of ethanol] per week; SDW) had a HR of 1.21 (95% CI 1.09–1.34) for AF compared to men in the lowest quartile (<0.90 SDW). In men, problem drinking was also associated with an increased AF risk (HR: 1.24; 95% CI: 1.10–1.39). Among women, AF risk was not significantly associated with alcohol consumption (P for trend 0.09 for decreasing risk of AF over quartiles of weekly alcohol consumption) or problem drinking (HR: 1.00; 95% CI 0.70–1.42).ConclusionSelf-reported alcohol consumption and problem drinking were associated with an increased risk of AF among men, but not in women.     

Observational studies on the effect of dietary antioxidants on asthma: a meta-analysis

Background and objective:   It has been suggested that the rapid increase in asthma prevalence may in part be due to a decrease in the intake of dietary antioxidants, including vitamin C, vitamin E and β-carotene. Epidemiological studies investigating the association between dietary antioxidant intake and asthma have generated inconsistent results. A meta-analysis was undertaken to examine the association between dietary antioxidant intake and the risk of asthma.
Methods:   The MEDLINE database was searched for observational studies in English-language journals from 1966 to March 2007. Data were extracted using standardized forms. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. Ten studies were eligible for inclusion. Seven studies, comprising 13 653 subjects, used asthma or wheeze as their outcome; three studies explored the effect of antioxidant intake on lung function.
Results:   A higher dietary intake of antioxidants was not associated with a lower risk of having asthma. The pooled OR for having asthma were 1.06 (95% CI: 0.79–1.43) for subjects with a higher dietary vitamin C intake compared with those with a lower intake; 0.88 (95% CI: 0.61–1.25) for vitamin E; and 1.12 (95% CI: 0.77–1.62) for β-carotene. There was no significant association between dietary antioxidant intake and lung function except for a positive association between vitamin C intake and an increase in FEV₁ (29.1 mL, 95% CI: −0.4–58.6, P  = 0.05).
Conclusions:   This meta-analysis does not support the hypothesis that dietary intake of the antioxidants vitamins C and E and β-carotene influences the risk of asthma.     

The association between meat intake and the risk of coronary heart disease in Korean men using the Framingham risk score: A prospective cohort study

Background and aimsResearch suggests that meat intake may increase the risk of coronary heart disease (CHD), but most studies take place in Western countries, where the types and amount of meat products consumed differ from those in Asian countries. We aimed to identify the association between meat intake and CHD risk in Korean male adults, using the Framingham risk score.Methods and resultsWe used data from the Korean Genome and Epidemiology Study (KoGES) Health Examinees (HEXA) study, including 13,293 Korean male adults. We estimated the association of meat intake with ≥20% 10-year CHD risk using Cox proportional hazards regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects with the highest total meat intake had a 53% (model 4: HR 1.53, 95% CI 1.05–2.21) increased 10-year CHD risk compared to those with the lowest intake. Those with the highest red meat intake had a 55% (model 3: HR 1.55, 95% CI 1.16–2.06) increased 10-year CHD risk compared to those with the lowest intake. No association was observed between poultry or processed meat intake and 10-year CHD risk.ConclusionsConsumption of total meat and red meat was associated with a higher risk of CHD in Korean male adults. Further studies are needed to provide criteria for the appropriate meat intake by meat type to reduce CHD risk.     

Entropy as a Measure of Myocardial Tissue Heterogeneity in Patients With Ventricular Arrhythmias

ObjectivesThe authors investigated the incremental prognostic value of entropy, a novel measure of myocardial tissue heterogeneity by cardiac magnetic resonance (CMR) imaging in patients presenting with ventricular arrhythmias (VAs).BackgroundCMR can characterize myocardial areas serving as arrhythmogenic substrate.MethodsConsecutive patients undergoing CMR imaging for VAs were followed for major adverse cardiac events (MACEs) defined by all-cause death, incident VAs requiring therapy, or heart failure hospitalization. Entropy was derived from the probability distribution of pixel signal intensities of the left ventricular (LV) myocardium.ResultsA total of 583 patients (age 54 ± 15 years, female 39%, left ventricular ejection fraction [LVEF] 54 ± 13%) were followed for a median of 4.4 years and experienced 141 MACEs. Entropy showed strong unadjusted association with MACE (HR: 1.88; 95% CI: 1.63-2.17; P < 0.001). In a multivariable model including LVEF, QRS duration, late gadolinium enhancement, and presenting arrhythmia, entropy maintained independent association with MACE (HR: 1.61; 95% CI: 1.32-1.96; P < 0.001). Entropy was further significantly associated with MACE in patients without myocardial scar (HR: 2.43; 95% CI: 1.55-3.82; P < 0.001) and in those presenting with nonsustained VAs (HR: 2.16; 95% CI: 1.43-3.25; P < 0.001). Addition of LV entropy to the baseline multivariable model significantly improved model performance (C-statistic improvement: 0.725 to 0.754; P = 0.003) and risk reclassification.ConclusionsIn patients with VAs, CMR-assessed LV entropy was independently associated with MACE and provided incremental prognostic value, on top of LVEF and late gadolinium enhancement. LV entropy assessment may help risk stratification in patients with absence of myocardial scar or with nonsustained VAs.     

Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study

BACKGROUND: Data on the influence of gonadal hormones on incident fracture risk in elderly men are limited. We prospectively examined the relationship between serum levels of testosterone and estradiol and future fracture risk in community-dwelling men. METHODS: A total of 609 men older than 60 years had been observed between January 1989 and December 2005, with the median duration being 5.8 years (up to 13 years). Clinical risk factors, including bone mineral density and lifestyle factors, were assessed at baseline. Serum testosterone and estradiol levels were measured by tandem mass spectrometry. The incidence of a low-trauma fracture was ascertained during follow-up. RESULTS: During follow-up, 113 men had at least 1 low-trauma fracture. The risk of fracture was significantly increased in men with reduced testosterone levels (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.09-1.62). After adjustment for sex hormone-binding globulin, serum testosterone (HR, 1.48; 95% CI, 1.22-1.78) and serum estradiol (HR, 1.21; 95% CI, 1.00-1.47) levels were associated with overall fracture risk. After further adjustment for major risk factors of fractures (age, weight or bone mineral density, fracture history, smoking status, calcium intake, and sex hormone-binding globulin), lower testosterone was still associated with increased risk of fracture, particularly with hip (HR, 1.88; 95% CI, 1.24-2.82) and nonvertebral (HR, 1.32; 95% CI, 1.03-1.68) fractures. CONCLUSION: In community-dwelling men older than 60 years, serum testosterone is independently associated with the risk of osteoporotic fracture and its measurement may provide additional clinical information for the assessment of fracture risk in elderly men.     

Lipoprotein(a), interleukin-10, C-reactive protein, and 8-year outcome after percutaneous coronary intervention

Background:

This prospective study investigated the association between preprocedural biomarker levels and incident major adverse cardiac events (MACE) in complex patients undergoing percutaneous coronary intervention (PCI) with sirolimus‐eluting stenting.

Hypothesis:

Lipoprotein(a) (Lp[a]), interleukin‐10 (IL‐10), and high‐sensitivity C‐reactive protein (CRP) have long‐term prognostic value in patients undergoing PCI.

Methods:

Between April 2002 and February 2003, 161 patients were included in the study. Blood was drawn before the procedure, and biomarkers were measured. Patients were followed‐up for MACE (death, nonfatal myocardial infarction, and repeat revascularization). Cox proportional hazard models were used to determine risk of MACE for tertiles of biomarkers. Both 1‐year and long‐term follow‐up (median, 6 years; maximum, 8 years) were evaluated.

Results:

Mean age was 59 years, and 68% were men. During long‐term follow‐up, 72 MACE occurred (overall crude cumulative incidence: 45% [95% confidence interval (CI): 37%‐52%]). Lp(a) was associated with a higher 1‐year risk of MACE, with an adjusted hazard ratio (HR) of 3.1 (95% CI: 1.1‐8.6) for the highest vs the lowest tertile. This association weakened and lost significance with long‐term follow‐up. IL‐10 showed a tendency toward an association with MACE. The 1‐year HR was 2.1 (95% CI: 0.92‐5.0). Long‐term follow‐up rendered a similar result. The association of CRP with MACE did not reach statistical significance at 1‐year follow‐up. However, CRP was associated with long‐term risk of MACE, with an HR of 1.9 (95% CI: 1.0‐3.5).

Conclusions:

In this prospective study, preprocedural Lp(a) level was associated with short‐term prognosis after PCI. The preprocedural CRP level was associated with long‐term prognosis after PCI. Clin. Cardiol. 2012 DOI: 10.1002/clc.21988 The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Low-carbohydrate diet and cardiovascular diseases in Iranian population: Tehran Lipid and Glucose Study

Background and aimsStudies indicated that the risk of cardiovascular disease (CVD) in association to greater adherence to low-carbohydrate diet (LCD) differs in various populations. In this study, we aimed to assess the association of LCD score with the risk of CVD events in a prospective population-based study.Methods and resultsCVD-free participants (n = 2188) were recruited from the Tehran Lipid and Glucose Study (2006–2008) and followed for a mean of 6.7 years. Using a valid and reliable 168 item semi-quantitative food frequency questionnaire, the LCD score was determined based on the percentage of energy as carbohydrate, protein, and fat, which ranged from 0 to 12. Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) of CVD across tertiles of LCD score in women and men.Mean ± SD age of participants (44.8% male) was 38.8 ± 13.0 years, and median (25–75, interquartile range) of the LCD score was 6 (4–8) at baseline. During follow-up, 77 (3.5%) new cases of CVD were identified. After adjustment for sex, age, body mass index, physical activity, smoking, energy intake, diabetes, and hypertension, there was no association between the LCD score and risk of CVD outcomes in all participants (HR = 0.93; 95% CI: 0.86–1.02) and women (HR = 1.13; 95% CI: 0.94–1.36); however, the LCD score was associated with an 11% reduced incidence of CVD events in men (HR = 0.89; 95% CI: 0.80–0.98), (P for trend: 0.028).ConclusionFindings showed that higher adherence to LCD may be associated with a lower risk of CVD outcomes in men but not in women.     

Serum copper-to-zinc ratio is associated with heart failure and improves risk prediction in middle-aged and older Caucasian men: A prospective study

Background and aimsSerum copper (Cu) and zinc (Zn) may play a role in the development of adverse cardiovascular outcomes including heart failure (HF). Serum Cu/Zn-ratio has been shown to be a risk indicator for cardiovascular disease, but its relationship with HF has not been previously investigated. We aimed to assess the association between Cu/Zn-ratio and incident HF risk using a prospective cohort study.Methods and resultsStudy participants were recruited in eastern Finland with baseline examinations carried out between March 1998 and December 2001. Serum levels of Cu and Zn were measured using atomic absorption spectrometry in 1866 men aged 42–61 years without a history of HF at baseline. Multivariable-adjusted hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident HF. During 26.5 years median follow-up, 365 HF cases occurred. Restricted cubic splines suggested linear relationships of serum Cu/Zn-ratio, Cu and Zn with HF risk. A unit increase in Cu/Zn-ratio was associated with an increased HF risk in analysis adjusted for several potential confounders including nutritional factors such as total energy intake, intake of fruits, berries and vegetables, and red meat (HR 1.63; 95% CI 1.06–2.51). The corresponding multivariable-adjusted HRs (95% CIs) for serum Cu and Zn were 2.42 (1.32–4.44) and 1.34 (0.50–3.63), respectively. Addition of Cu/Zn-ratio to a HF risk prediction model was associated with improved risk prediction.ConclusionIn middle-aged and older Finnish men, increased serum Cu/Zn-ratio is associated with an increased risk of HF in a linear dose-response fashion and might improve HF risk assessment.