Discrepancy between results of randomized control studies and retrospective analysis: The case of statin therapy effect on one-year mortality in patients with decompensated heart failure

BackgroundIn view of the recent reports on a lack of protective effect of statin therapy on clinical outcomes in patients with heart failure, the present study investigated the impact of statin therapy before admission on one-year survival of patients hospitalized due to decompensated heart failure in two groups of patients; with and without ischemic heart disease.MethodsWe performed a retrospective cohort analysis of 887 consecutive patients older than 18 years hospitalized with decompensated heart failure between 11/December 2001 and 06/June 2005. Two groups of patients were compared: those who received statins within 3 months before the admission (S) and those who did not (NS). The primary outcome was one-year all-cause mortality. To adjust for a potential misbalance between S and NS groups in baseline characteristics, a propensity score for statin therapy was incorporated into the survival model.ResultsTwo hundred eighty-one patients (31.7%) received statins prior to admission. Patients with ischemic heart disease (IHD) (656/887 subjects, 74%) had higher rate of S therapy as compared to the rest 36.3% vs. 18.6%, p < 0.001. Overall one-year mortality rate in the S group was 21% vs. 31.8% in the NS group, p < 0.001. In the subgroup of patients with IHD, statins were protective after adjustment for comorbidities and propensity score (hazard ratio [HR], 0.66; 95% CI 0.4–0.97), but in patients with non-ischemic HF statin therapy was not associated with a protective effect (HR 0.77; 95% CI 0.38–1.6).ConclusionsIn our study statins' protective effect on one-year survival in HF patients is restricted to patients with IHD. This stands in disagreement with the results of the randomized trials showing no effect of statin therapy. Statin use may be a marker of better health care and despite an extensive adjustment for baseline characteristics, unaccounted bias inherent to retrospective studies may explain the discrepancy in the results.     

Inflammation-sensitive plasma proteins are associated with increased incidence of heart failure: a population-based cohort study

BackgroundAlthough inflammation has been associated with different cardiovascular diseases, the relationships with future heart failure (HF) are unclear. This population-based study explored whether elevated plasma levels of inflammatory proteins are associated with incidence of HF.MethodsFive inflammation-sensitive plasma proteins (ISPs, fibrinogen, ceruloplasmin, haptoglobin, orosomucoid, and α1-antitrypsin) was measured in 6071 men (mean age 46 years) without history of myocardial infarction (MI) or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 22 years of follow-up, in relation to the number of elevated ISPs (i.e., in the 4th quartile). Subjects with myocardial infarction during follow-up were censored.ResultsDuring the follow-up, 159 men were hospitalized due to HF. Baseline levels of all ISPs, except for haptoglobin, were significantly higher in men who developed HF. After adjustments for confounding factors, the hazard ratios (HR) of HF were 1.00 (reference), 1.7 (95% CI: 1.1–2.7), 2.0 (CI: 1.2–3.3) and 2.6 (CI: 1.6–4.1), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (trend: p < 0.001). Of the individual ISPs, fibrinogen, ceruloplasmin and α1-antitrypsin showed significant relationships with incidence of HF after adjustment for risk factors.ConclusionPlasma levels of inflammatory markers are associated with long-term incidence of hospitalizations due to HF in middle-aged men.     

Gender differences in epicardial and tissue-level reperfusion in patients undergoing primary angioplasty for acute myocardial infarction

ObjectivePregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients.MethodBlood samples were drawn at study entry. Serum PAPP-A values ≥4 mIU/L were considered elevated. Mortality and non-fatal myocardial infarction was prospectively registered. The primary outcome was the composite outcome of myocardial infarction and all-cause mortality, secondary outcomes were all-cause mortality and myocardial infarction.ResultsPatients (n = 4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62–2.45, p < 0.0005), all-cause mortality (HR 2.42, 1.92–3.06, p < 0.0005), and myocardial infarction (HR 1.40, 1.01–1.94, p = 0.046). After Holm's correction, the latter significance disappeared. After adjustment for risk factors and medication at entry, elevated PAPP-A remained significantly related to the composite outcome (HR 1.51, 1.22–1.86, p < 0.0005) and all-cause mortality (HR 1.68, 1.32–2.13, p < 0.0005).ConclusionIn patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death.     

Predictive value of white blood cell subtypes for long-term outcome following myocardial infarction

IntroductionElevation of total white blood cells (WBC) count is associated with higher mortality in patients with acute coronary syndromes. However, it is unknown which specific subset of leukocytes best correlates with increased risk of adverse outcome.Methods and resultsWe prospectively studied the predictive value of WBC subtypes for long-term outcome in 1037 patients with acute myocardial infarction (AMI). Total WBC, neutrophil, monocyte and lymphocyte counts, and high-sensitivity C-reactive protein (CRP) were obtained in each patient. The median duration of follow up was 23 months (range, 6–42 months). Analyzed separately, baseline total WBC (HR 2.2, 95% CI 1.5–3.3; P < 0.0001), neutrophil (HR 2.7, 95% CI 1.8–4.1; P < 0.0001) and monocyte (HR 1.9, 95% CI 1.3–2.8; P = 0.001) counts in the upper quartile, and lymphocyte count in the lower quartile (HR 1.5, 95% CI 1.1–2.3; P = 0.03), were all independent predictors of mortality. Comparing nested models, adding other WBC data failed to improve model based on neutrophil count. In contrast, adding neutrophil count to the models based on total WBC (P = 0.01), on monocyte count (P < 0.0001) or on lymphocyte count (P < 0.0001) improved the prediction of the models. Neutrophil count in the upper quartile (≥9800 μL^?1) remained a strong independent predictor of mortality after adjustment for left ventricular systolic function and for CRP (HR 2.2, 95% CI 1.6–3.0; P < 0.0001).ConclusionOf all WBC subtypes, elevated neutrophil count best correlates with mortality in patients with AMI. Neutrophil count provides additive prognostic information when combined with CRP.     

Factors associated with in-hospital mortality in patients with acute aortic syndrome involving the ascending aorta

BackgroundAortic intramural hematoma (IMH), a variant form of classic dissection (AD), is an increasingly recognized and potentially fatal entity of acute aortic syndrome (AAS). We sought to assess the real impact of increased recognition of IMH on mortality of AAS involving the ascending aorta.MethodsWe evaluated 186 consecutive patients with AAS involving the ascending aorta (57.0 ± 13.5 years, 95 females) admitted between January 1993 and March 2003.ResultsFinal diagnosis was AD in 135 patients and IMH in 51 (27%). Patients with AD were younger (54.0 ± 13 vs. 65.6 ± 10.7 years, p < 0.05) and surgery was more frequently performed (82% vs. 31%, p < 0.001). Overall in-hospital mortality was 16% (30/186); both total mortality (19% vs. 8%, p = 0.059) and mortality without surgery (71% vs. 9%, p < 0.001) was higher in AD. Logistic regression identified the following presenting variables as predictors of mortality: AD (OR 53.0; 95% CI, 6.6–425.4; p < 0.001), confusion/coma (OR 20.1; 95% CI, 3.8–107.8; p < 0.001), tamponade (OR 5.3; 95% CI, 1.2–24.3; p = 0.031), heart failure (OR 8.1; 95% CI, 1.1–61.0; p = 0.043), and medical treatment only (OR 17.6; 95% CI, 4.6–67.6, p < 0.001). Tamponade was more prevalent in IMH (25% vs. 11%, p = 0.038), and was a predictor of higher mortality in both groups.ConclusionIMH comprises of significant proportion of AAS involving the ascending aorta and is an independent variable associated with lower mortality despite lower frequency of surgery. Treatment option including optimal timing of surgery can be individualized based on underlying disease entity of AAS and some clinical features at the initial presentation.     

Plasma levels of antibodies against oxidized LDL are inherited but not associated with HDL-cholesterol level in families with early coronary heart disease

AimsThus far, the prognostic value of reverse left ventricular (LV) remodeling after ST-elevation acute myocardial infarction (STEMI) has not been fully evaluated. We sought to investigate the incidence, major determinants, and long-term clinical significance of reverse LV remodeling in a large series of STEMI patients successfully treated with primary percutaneous coronary intervention (P-PCI).Methods and resultsSerial complete 2D-echocardiograms were obtained within 24 h after P-PCI, and at 1 and 6 months in 512 consecutive reperfused STEMI patients. Reverse remodeling was defined as a reduction >10% in LV end-systolic volume (LVESV) at 6 month follow-up. Reverse LV remodeling occurred in 49% of study population. At follow-up (41.6 ± 23 months), late heart failure (HF) rate was significantly higher among patients without reverse LV remodeling as compared with those with it (32% vs. 11%, P < 0.0001). At multivariate analysis, independent predictors of reverse LV remodeling were a small infarct size measured as peak creatine kinase value (P < 0.0001), a small functional myocardial damage measured as wall motion score index within the infarct zone (P = 0.018) and baseline LVESV (P < 0.0001). After adjustment for several clinical, echographic and angiographic variables, Cox analysis identified reverse LV remodeling as the only beneficial independent predictor of long-term heart failure-free survival (HR: 0.44, 95% CI: 0.275–0.722).ConclusionsReverse LV remodeling occurred in half of successfully reperfused STEMI patients. Small structural and functional myocardial damages within the infarct zone are the major determinants of reverse LV remodeling. As expression of effective myocardial salvage by P-PCI, the reverse remodeling is an important predictor of favorable long-term outcome.     

Slow heart rate recovery after exercise is associated with carotid atherosclerosis

ObjectiveSlow heart rate recovery (HRR) after exercise is an estimate of impaired parasympathetic tone and predictor of all-cause and cardiovascular mortality. Carotid atherosclerosis is associated with high risk of developing coronary heart disease (CHD) and stroke. We tested the hypothesis that slow HRR is associated with carotid atherosclerosis in a cross-sectional study of 12,712 middle-aged men (age 49.1 ± 8.9 years).MethodsCarotid atherosclerosis was measured using B-mode ultrasonography and defined as stenosis >25% and/or intima–media thickness >1.2 mm. HRR was calculated as the difference between peak heart rate during a graded exercise treadmill test and heart rate 2 min after cessation of exercise.ResultsThe prevalence of carotid atherosclerosis was 8.4%. The prevalence of atherosclerosis was significantly higher among subjects in the lowest (<44 bpm) versus the highest (>61 bpm) quartile of HRR (14.4% versus 4.1%, p < 0.001). In multivariable logistic regression models adjusted for established CHD risk factors, inflammatory markers, and exercise capacity, subjects in the lowest quartile of HRR (<44 bpm) were 1.50 times (95% CI: 1.13–2.00) more likely to have carotid atherosclerosis than subjects in the highest quartile (HRR >61 bpm).ConclusionsSlow heart rate recovery after exercise, an index of decreased parasympathetic activity, is associated with carotid atherosclerosis independent of established risk factors in middle-age men.     

Effect of beta blocker therapy on survival of patients with heart failure and preserved systolic function following hospitalization with acute decompensated heart failure

BackgroundThe importance of heart failure with preserved ejection fraction is being increasingly recognized. However, there is a paucity of data about effective treatment for this condition. The present study investigated the impact of beta blocker therapy for 3 months before admission on the two-year survival of patients with heart failure and preserved systolic function hospitalized due to decompensated heart failure.MethodsWe performed a retrospective cohort analysis of 345 consecutive patients with heart failure with preserved systolic function older than 18 years hospitalized due to decompensated heart failure. Two groups of patients were compared: those who received beta blockers within 3 months before admission (BB) and those who did not (NBB). The primary outcome was two year all cause mortality (maximal follow-up available in all subjects). To adjust for a potential misbalance between BB and NBB groups in baseline characteristics, a propensity score for beta blocker therapy was incorporated into the survival model.Results154 patients (44.6%) received beta blockers prior to admission. Overall two year mortality rate in the BB group was 50% vs. 62.8% in the NBB group, log-rank test p = 0.016. Beta blockers showed protective effect on two-year survival after adjustment for comorbidities and propensity score (hazard ratio [HR], 0.69; 95% CI 0.47–0.99).ConclusionsTherapy with beta blockers may have protective effect on survival of patients with heart failure with preserved systolic function.     

Adiponectin G276T gene polymorphism is associated with cardiovascular disease in Japanese patients with type 2 diabetes

ObjectiveAdiponectin has anti-atherogenic properties and reduced serum adiponectin levels are associated with cardiovascular disease (CVD). In this study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene G276T polymorphism that is associated with serum adiponectin level in a large cohort of type 2 diabetic patients.Research design and methodsWe enrolled 2637 Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9 ± 7.9 years old), determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated the association between this polymorphism and the prevalence of CVD (myocardial infarction and/or cerebral infarction).ResultsThe prevalence of CVD tended to be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%), p value for trend = 0.0059] and was significantly higher in the subjects with GG genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p = 0.0060). Multiple logistic regression analyses revealed that the number of G alleles (Odds ratio (OR) = 1.49 with 95%CI 1.09–2.05, p = 0.0125) and GG genotype (OR = 1.66 with 95%CI 1.13–2.43, p = 0.0098) were significantly associated with CVD even after adjustment for conventional risk factors. Interestingly, the presence of obesity further and significantly increased the risk of CVD in the subjects with GG genotype (OR = 1.67 with 95%CI 1.14–2.44, p = 0.0090) but not in the subjects with TT or GT genotype (OR = 1.17 with 95%CI 0.73–1.89, NS).ConclusionsIt is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity.     

Benefits from intracoronary as compared to intravenous abciximab administration for STEMI patients undergoing primary angioplasty: a meta-analysis of 8 randomized trials

BackgroundAdjunctive abciximab administration has been demonstrated to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over IV route. Therefore, the aim of the current study was to perform a meta-analysis of randomized trials (RCTs) to assess the clinical efficacy and safety of IC vs IV abciximab administration in STEMI patients undergoing primary angioplasty.MethodsWe obtained results from all RCTs enrolling STEMI patients undergoing primary percutaneous coronary intervention (PCI). The primary endpoint was mortality, while recurrent myocardial infarction, postprocedural epicardial (TIMI 3) and myocardial (MBG 2–3) perfusion were identified as secondary endpoints. The safety endpoint was the risk of major bleeding complications.ResultsA total of 8 randomized trials were finally included in the meta-analysis, enrolling a total of 3259 patients. As compared to IV route, IC abciximab was associated with a significant improvement in myocardial perfusion (OR [95% CI] = 1.76 [1.28–2.42], p < 0.001), without significant benefits in terms of mortality (OR [95% CI] = 0.85 [0.59–1.23], p = 0.39), reinfarction (OR [95% CI] = 0.79 [0.46–1.33], p = 0.37), or major bleeding complications (OR [95% CI] = 1.19 [0.76–1.87], p = 0.44). However, we observed a significant relationship between patient's risk profile and mortality benefits from IC abciximab administration (p = 0.011).ConclusionsThe present updated meta-analysis showed that IC administration of abciximab is associated with significant benefits in myocardial perfusion, but not in clinical outcome at short-term follow-up as compared to IV abciximab administration, without any excess of major bleedings in STEMI patients undergoing primary PCI. However, a significant relationship was observed between patient's risk profile and mortality benefits from IC abciximab administration. Therefore, waiting for long-term follow-up results and additional randomized trials, IC abciximab administration cannot be routinely recommended, but may be considered in high-risk patients.     

Plasma osteoprotegerin level on admission is associated with no-reflow phenomenon after primary angioplasty and subsequent left ventricular remodeling in patients with acute ST-segment elevation myocardial infarction

ObjectivesOsteoprotegerin (OPG) upregulates endothelial cell adhesion molecule response to TNF-α by upregulating angiopoietin-2 (Ang-2). The aim of this study was to investigate the association between admission plasma levels of OPG, Ang-2 and TNF-α in patients with acute ST-segment elevation myocardial infarction (STEMI) and no-reflow after primary angioplasty and subsequent left ventricular remodeling (LVR).MethodsNinety-two patients with first STEMIs, reperfused within 12 h of symptom onset, were included. LVR was defined as a >20% increase in LV end-diastolic volume at 6-month follow-up assessed using echocardiography.ResultsThe incidences of angiographic no-reflow and electrocardiographic no-reflow were 40.2% and 55.4%, respectively. Thirty-six percent of patients subsequently developed LVR. OPG levels were significantly higher in patients who developed angiographic no-reflow (173 pg/ml, interquartile range [IQR] 83–416 vs 104 pg/ml, IQR 57–235; p = 0.04), electrocardiographic no-reflow (160 pg/ml, IQR 81–315 vs 102 pg/ml, IQR 47–230; p = 0.025) and LVR (174 pg/ml, IQR 120–342 vs 97 pg/ml, IQR 51–219; p = 0.004). In multivariable logistic regression, OPG level was an independent predictor of angiographic (OR 1.05: 95% CI 1.01–1.08 [per 10 pg/ml increase]; p = 0.005) and electrocardiographic (OR 1.04: 95% CI 1.00–1.07 [per 10 pg/ml increase]; p = 0.04) no-reflow. ROC analysis showed an area under the curve of 0.69 for OPG and LVR. Plasma OPG ≥ 132 pg/ml showed a sensitivity of 72% and a specificity of 61% for predicting LVR (OR 4.05: 95% CI 1.06–15.38; p = 0.04).ConclusionHigh OPG level on admission is significantly associated with no-reflow after primary angioplasty and subsequent LVR at follow-up in patients with STEMI.     

The association of tooth scaling and decreased cardiovascular disease: a nationwide population-based study

ObjectivePoor oral hygiene has been associated with an increased risk for cardiovascular disease. However, the association between preventive dentistry and cardiovascular risk reduction has remained undetermined. The aim of this study is to investigate the association between tooth scaling and the risk of cardiovascular events by using a nationwide, population-based study and a prospective cohort design.MethodsOur analyses were conducted using information from a random sample of 1 million persons enrolled in the nationally representative Taiwan National Health Insurance Research Database. Exposed individuals consisted of all subjects who were aged ≥ 50 years and who received at least 1 tooth scaling in 2000. The comparison group of non-exposed persons consisted of persons who did not undergo tooth scaling and were matched to exposed individuals using propensity score matching by the time of enrollment, age, gender, history of coronary artery disease, diabetes, hypertension, and hyperlipidemia.ResultsDuring an average follow-up period of 7 years, 10,887 subjects who had ever received tooth scaling (exposed group) and 10,989 age-, gender-, and comorbidity-matched subjects who had not received tooth scaling (non-exposed group) were enrolled. The exposed group had a lower incidence of acute myocardial infarction (1.6% vs 2.2%, P < .001), stroke (8.9% vs 10%, P = .03), and total cardiovascular events (10% vs 11.6%, P < .001) when compared with the non-exposed group. After multivariate analysis, tooth scaling was an independent factor associated with less risk of developing future myocardial infarction (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.57-0.85), stroke (HR, 0.85; 95% CI, 0.78-0.93), and total cardiovascular events (HR, 0.84; 95% CI, 0.77-0.91). Furthermore, when compared with the non-exposed group, increasing frequency of tooth scaling correlated with a higher risk reduction of acute myocardial infarction, stroke, and total cardiovascular events (P for trend < .001).ConclusionTooth scaling was associated with a decreased risk for future cardiovascular events.     

Family history of coronary heart disease, health care and health behaviors

IntroductionPrevious studies on health care and health behaviors in individuals with a family history of coronary heart disease (CHD) have produced contradictory results, and there is still no evidence that these individuals are more aware of their risk and have improved health behaviors and heath care. This study aims to evaluate health care and health behaviors according to family history of CHD.MethodsIndividuals randomly selected from the general population living in Porto, Portugal, aged ≥18 years (evaluation period: 1999–2003), and without prior history of chronic diseases (n = 764), were evaluated by questionnaires on family and personal disease history, health care and health behaviors. A family history of CHD was defined as the occurrence of acute myocardial infarction or sudden death in at least one first-degree relative. Odds ratios and 95% confidence intervals (OR, 95% CI) were calculated using unconditional logistic regression after stratification for age (18–39 vs. ≥40 years) and education (≤6 vs. >6 years schooling).ResultsAmong men, 20% reported a family history of CHD, approximately the same proportion as in women (19.4%) (p = 0.900). The proportion of subjects with a family history of CHD was significantly higher in older (≥40 vs. 18–39 years: 25.0% vs. 12.0%, p < 0.001) and less educated individuals (>6 vs. ≤6 years: 27.0% vs. 17.1%, p = 0.004). Overall, no significant associations were found between health care and behaviors and CHD family history. Only in younger individuals, after adjustment for education, was a significant positive association found between 1–2 dental visits and CHD family history (OR=2.92; 95% CI: 1.27–6.70). Younger subjects who smoked and consumed alcohol and caffeine also presented a higher probability of having CHD family history, but the associations were not statistically significant.Discussion and conclusionsIn this population without disease requiring regular medical care, individuals with CHD family history had similar care-seeking patterns and health behaviors to those without. These results suggest a lack of awareness of their increased risk and highlight the importance of developing measures to promote sustained and effective changes in risk factors in individuals with genetic susceptibility to CHD.     

The relation of serum gamma-glutamyl transferase levels with coronary lesion complexity and long-term outcome in patients with stable coronary artery disease

BackgroundRelation of serum gamma-glutamyl transferase (GGT) levels with extent, severity, and complexity of coronary artery disease has not been adequately studied. Therefore, we evaluated the relationship between GGT levels and coronary complexity, severity and extent assessed by SYNTAX score and long-term adverse events.MethodsWe enrolled 442 consecutive patients with stable angina pectoris who underwent coronary angiography. Baseline serum GGT levels were measured and SYNTAX score was calculated from the study population. Median follow-up duration was 363 days. Endpoints were all cause mortality and any revascularization.ResultsGGT levels demonstrated an increase from low SYNTAX tertile to high tertile. In multivariate analysis serum GGT, diabetes mellitus, HDL-cholesterol, eGFR and ejection fraction were found to be independent predictors of high SYNTAX score. The survival analysis showed that long-term revascularization rates were comparable between the GGT groups (for 36 U/l cut point) of the overall population (7.7% vs 8.6% logrank, p = 0.577), whereas long-term all cause mortality rate was higher in the GGT ≥ 36 U/l group (3.6% vs 11.6% logrank, p = 0.001). In Cox proportional hazards regression model, GGT ≥ 36 U/l group was found to be an independent predictor of long-term all cause mortality in the unadjusted (HR 2.54, 95% CI 1.17–5.48, p = 0.018) and age- and gender-adjusted (HR 2.58, 95% CI 1.19–5.58, p = 0.016) models.ConclusionSerum GGT level was independently associated with coronary complexity and long-term mortality in patients with stable coronary artery disease.     

Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis

BackgroundConflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease.AimsTo identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations.MethodsA systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models.ResultsOf the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33–2.12; I² = 69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08–1.50; I² = 38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26–3.39; I² = 78%); stroke (HR 1.59, 95% CI 1.29–1.96; I² = 45%); sudden cardiac death (HR 1.60, 95% CI 1.14–2.25; I² = 68%); and atrial fibrillation (HR 1.55, 95% CI 1.31–1.83; I² = 0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population.ConclusionQTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.     

Telomerase, telomere length, and coronary artery calcium in black and white men in the CARDIA study

ObjectiveTo evaluate whether telomerase activity, measured in circulating blood leukocytes, might be associated with prevalent atherosclerosis, or predict future coronary artery disease risk.Methods and resultsWe examined associations of telomerase activity levels measured at year 15 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with prevalent coronary artery calcium (CAC), progressive CAC at year 20, and incident CAC between years 15 and 20, in 440 black and white men aged 33–45 years. Telomere length was also measured in a subset of participants (N = 129).In multivariate-adjusted analysis, higher quartiles of telomerase were cross-sectionally associated with greater odds of prevalent CAC at year 15 (quartile 2: OR = 1.32, 95% CI: 0.54–3.23; quartile 3: OR = 1.40, 95% CI: 0.60–3.30; quartile 4: OR = 3.27, 95% CI: 1.39–7.71 compared with quartile 1, p-continuous = 0.012) and progressive CAC at year 20, but telomerase was not significantly associated with incidence of newly detectable CAC. Higher telomerase activity levels predicted greater CAC progression at year 20 among persons with short telomere length; low telomerase and short TL predicted less CAC progression.ConclusionTelomerase activity in leukocytes was associated with calcified atherosclerotic plaque, and was also a predictor of advancing plaque among persons with short telomeres.     

The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: an observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes

AimsTo elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance.MethodsContinuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden.ResultsIn 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p = 0.032), although average risk versus non-glargine was non-significantly higher (HR 1.37, 95% CI 0.78–2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p = 0.35) and the mean risk was similar for glargine and non-glargine (p = 0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p = 0.037) and breast cancer (p = 0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59–0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78–1.14) compared to the general population and did not change with longer diabetes duration (p = 0.68 and p = 0.53 respectively).ConclusionsAnalysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research.     

Age and Gender Differences in Quality of Care and Outcomes for Patients with ST-segment Elevation Myocardial Infarction

BackgroundYoung patients (aged ≤ 45 years) presenting with ST-segment elevation myocardial infarction present unique challenges. The quality of care and in-hospital outcomes may differ from their older counterparts.MethodsA total of 31,544 patients presenting with ST-segment elevation myocardial infarction and enrolled in the American Heart Association's Get With the Guidelines Coronary Artery Disease registry were analyzed. The cohort was divided into those aged 45 years or less and those aged more than 45 years.ResultsYoung patients accounted for 10.3% of all ST-segment elevation myocardial infarction cases. Compared with older patients, younger patients were less likely to have traditional cardiovascular risk factors and had similar or better quality/performance measures with lower in-hospital mortality (unadjusted rate 1.6 vs 6.5%, P <.0001; adjusted odds ratio [OR], 0.37; 95% confidence interval [CI], 0.29-0.46). Time trend analysis (2002-2008) suggested an increase over time in the “all or none” composite performance measure in both the younger and older patients (68%-97% and 69%-96%, respectively). However, there was significantly lower quality of care and worse outcomes in women (vs men) and in the very young (≤35 vs 36-45 years). Significant interaction was seen between age and gender for in-hospital death, such that the gender difference was greater in the younger cohort. Similar interaction was seen for door-to-thrombolytic time such that the gender delay was greater in the younger cohort (women:men ratio of means = 1.73, 95% CI, 1.21-2.45 [younger] vs 1.08, 95% CI, 1.00-1.18 [older]; P_interaction = .0031).ConclusionYoung patients aged 45 years or less presenting with ST-segment elevation myocardial infarction overall had similar quality of care and in-hospital outcomes as older counterparts. However, quality of care was significantly lower and mortality was higher in young women (vs young men) and the very young (≤35 vs 36-45 years).