Risk Factor For Cardiovascular Death Research Articles

Elevated D-dimer levels predict an adverse outcome in hospitalized patients with acute decompensated heart failure

Patients with heart failure possess coagulation disorders and a risk of thromboembolic events in the vascular system. This risk could potentially be derived from many sources such as inflammation, neuro-hormonal activation, endothelial dysfunction, and stasis [ 1 Lip G.Y. Gibbs C.R. Does heart failure confer a hypercoagulable state? Virchow's triad revisited. J Am Coll Cardiol. 1999; 33: 1424-1426 Abstract Full Text PDF PubMed Scopus (309) Google Scholar , 2 Zannad F. Stough W.G. Regnault V. et al. Is thrombosis a contributor to heart failure pathophysiology? Possible mechanisms, therapeutic opportunities, and clinical investigation challenges. Int J Cardiol. 2013; 167: 1772-1782 Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar ]. D-dimer, a marker of fibrin turnover, is elevated where there is thrombus formation and/or resolution in the circulatory system, and exhibits many interesting properties as a biological marker of hemostatic abnormalities and thrombosis [ [3] Koracevic G.P. Pragmatic classification of the causes of high D-dimer. Am. J. Emerg. Med. 2009; 27 (e5–7): 1016 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar ]. Previous studies have shown that elevated D-dimer levels are present in patients with cardiovascular disease [ 4 Yamamoto K. Ikeda U. Furuhashi K. Irokawa M. Nakayama T. Shimada K. The coagulation system is activated in idiopathic cardiomyopathy. J Am Coll Cardiol. 1995; 25: 1634-1640 Abstract Full Text PDF PubMed Scopus (142) Google Scholar , 5 Morange P.E. Bickel C. Nicaud V. et al. Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study. Arterioscler Thromb Vasc Biol. 2006; 26: 2793-2799 Crossref PubMed Scopus (86) Google Scholar ], and several studies have suggested that elevated D-dimer levels are associated with long-term adverse outcomes in patients with established chronic and/or systolic heart failure [ 6 Alehagen U. Dahlstrom U. Lindahl T.L. Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure. Thromb Haemost. 2004; 92: 1250-1258 PubMed Google Scholar , 7 Zorlu A. Yilmaz M.B. Yucel H. Bektasoglu G. Refiker Ege M. Tandogan I. Increased D-dimer levels predict cardiovascular mortality in patients with systolic heart failure. J Thromb Thrombolysis. 2012; 33: 322-328 Crossref PubMed Scopus (27) Google Scholar ]. However, the short- and medium-term prognostic value of D-dimer levels on admission in hospitalized patients with acute decompensated heart failure (ADHF) is not well established. Therefore, this study aimed to analyze the in-hospital and medium-term prognostic value of elevated D-dimer levels in patients who were admitted to a cardiac intensive care unit with ADHF.

From bench to bedside: Can the improvements in left ventricular assist device design mitigate adverse events and increase survival?

ObjectiveIn vitro tests demonstrated that the new cone-bearing configuration of the Jarvik 2000 (Jarvik Heart Inc, New York, NY) left ventricular assist device exhibits better hydraulic efficiency than the previous pin-bearing design. We investigated the long-term outcomes of patients who received the Jarvik 2000 left ventricular assist device, depending on bearing design. MethodsA retrospective review of prospectively collected data from 18 centers included in the Italian Registry was performed. From May 2008 to September 2013, 99 patients with end-stage heart failure were enrolled. Patients were divided into 2 groups according to their Jarvik 2000 suspending mechanism: Group pin included patients with pin bearings (May 2008 to June 2010), and group cone included patients with newer cone bearings (July 2010 to September 2013). The 2 groups did not differ significantly in terms of baseline characteristics. ResultsA total of 30 of 39 patients (group pin) and 46 of 60 patients (group cone) were discharged. During follow-up, 6 patients underwent transplantation, and in 1 patient the left ventricular assist device was explanted. The cumulative incidence competing risk of the entire cohort for noncardiovascular-related death was 28% (20%-40%); the cumulative incidence competing risk for cardiovascular-related death was 56% (42%-73%): 71% in group pin versus 26% in group cone (P = .034). The multivariate analyses confirmed that the pin-bearing design was a risk factor for cardiovascular death, along with Interagency Registry for Mechanically Assisted Circulatory Support class. Right ventricular failures and ischemic and hemorrhagic strokes were significantly higher in group pin. ConclusionsPatients with the new pump configuration showed a better freedom from cardiovascular death and lower incidence of fatal stroke and right ventricular failure. Further studies are needed to prove the favorable impact of pump-enhanced fluid dynamics on long-term results.

The Prevalence of Clinical and Electrocardiographic Risk Factors of Cardiovascular Death Among On-duty Professional Firefighters.

Firefighters have twice as many cardiovascular deaths as police officers and 4 times as many as emergency medical responders. The etiology for this high rate of mortality remains unknown. The electrocardiogram (ECG) is a widely used tool to screen populations at risk, yet there are no available on-duty, high-resolution ECG recordings from firefighters. We sought to evaluate the prevalence of clinical and ECG risk factors among on-duty professional firefighters during 12-lead ECG holter monitoring and exercise stress testing. Firefighters were recruited from Surveying & Assessing Firefighters Fitness & Electrocardiogram (SAFFE) study. This descriptive study recruited firefighters from 7 firehouses across Upstate New York who completed on-duty 24-hour Holter ECG monitoring and a standard exercise stress test. All analyses were completed by a reviewer blinded to all clinical data. A total of 112 firefighters (mean [SD] age, 44 [8] years; mostly white men) completed the study. Although all firefighters were in normal sinus rhythm, more than half of them had at least 1 high-risk ECG risk factor present, including abnormal sympathetic tone (elevated heart rate, 54%), abnormal repolarization (wide QRS-T angle, 25%), myocardial scarring (fragmented QRS, 24%), and myocardial ischemia (ST depression, 24%). Most firefighters tolerated the treadmill exercise stress test well (metabolic equivalent tasks, 11.8 + 2.5]); however, almost one-third had abnormal results of stress tests that required further evaluation to rule out subclinical coronary artery disease. Among on-duty professional firefighters, high-risk ECG markers of fatal cardiac events and abnormal stress test results that warrant further evaluation are prevalent. Annual physical checkups with routine 12-lead ECG can identify those who might benefit from preventive cardiovascular services.

Electrocardiographic Measures and Prediction of Cardiovascular and Noncardiovascular Death in CKD.

Limited studies have assessed the resting 12-lead electrocardiogram (ECG) as a screening test in intermediate risk populations. We evaluated whether a panel of common ECG parameters are independent predictors of mortality risk in a prospective cohort of participants with CKD. The Chronic Renal Insufficiency Cohort (CRIC) study enrolled 3939 participants with eGFR<70 ml/min per 1.73 m(2) from June 2003 to September 2008. Over a median follow-up of 7.5 years, 750 participants died. After adjudicating the initial 497 deaths, we identified 256 cardiovascular and 241 noncardiovascular deaths. ECG metrics were independent risk markers for cardiovascular death (hazard ratio, 95% confidence interval): PR interval ≥200 ms (1.62, 1.19-2.19); QRS interval 100-119 ms (1.64, 1.20-2.25) and ≥120 ms (1.75, 1.17-2.62); corrected QT (QTc) interval ≥450 ms in men or ≥460 ms in women (1.72, 1.19-2.49); and heart rate 60-90 beats per minute (1.21, 0.89-1.63) and ≥90 beats per minute (2.35, 1.03-5.33). Most ECG measures were stronger markers of risk for cardiovascular death than for all-cause mortality or noncardiovascular death. Adding these intervals to a comprehensive model of cardiorenal risk factors increased the C-statistic for cardiovascular death from 0.77 to 0.81 (P<0.001). Furthermore, adding ECG metrics to the model adjusted for standard risk factors resulted in a net reclassification of 12.1% (95% confidence interval 8.1%-16.0%). These data suggest common ECG metrics are independent risk factors for cardiovascular death and enhance the ability to predict death events in a population with CKD.

Transplant-Associated Renal Microangiopathy Is Associated with a High Risk of Refractory Gvhd and Characterized By a Specific Biomarker Signature

IntroductionThere is increasing evidence that endothelial damage is involved in the pathogenesis of steroid-refractory graft-versus-host disease (refGVHD). Recently, serum soluble ST2 (suppressor of tumorigenicity,IL-33 receptor), an independent risk factor of cardiovascular death, has been identified as a risk factor of refractory GVHD. However, the pathomechanism of endothelial cell dysfunction which is associated with mortality from GVHD is yet poorly characterized. Renal transplant-associated microangiopathy (TMA) is another endothelial complication of alloSCT, and its association with severe GVHD and with biomarkers of endothelial damage (ST2, sCD141 (soluble thrombomodulin)), and endothelial function (VEGF) is investigated in this study.MethodsEvidence for renal TMA was studied in a cohort of 508 patients who underwent alloSCT between 2002 and 2013 at our institution and who have provided informed consent for this observational study. Criteria to diagnose renal TMA included an otherwise unexplained 50% rise in creatinine and lactate dehydrogenase (LDH) levels (or a pre-existing LDH above 400 U/L), a 50% drop in platelet counts (or a pre-existing platelet count below 50/nl) and at least 4% schistocytes. Cytokines were measured in sera taken prior to alloSCT and on the indicated days thereafter and stored at minus 80C. ST2 and sTM were measured by Duo Set ELISA (R&D) whereas VEGF was quantified by the multiplex protein array technology (Luminex). Statistical analyses were performed using SPSS19 and included a cumulative incidence analysis of cause-specific hazards and the non-parametrical median test of independent probes.ResultsBoth renal TMA and refGVHD were rare complications after alloSCT but were significantly associated with each other (TMA only 18/508 (3.5%), refGVHD only 26/508 (5.1%), both 20/508 (3.9%), chi2 0.000). Median time intervals from alloSCT to renal TMA and refGVHD were 1.93 (0.23-60.16) months and 1.23 (0.16-12.4) months respectively. In the overlap group, GVHD onset usually occurred before renal TMA (-0.69 months, -55.4 to 11.2) NRM rates were significantly increased in all three cohorts but approached 100% in patients with both complications (Figure 1).Serum sTM levels as well as soluble ST2 levels increased between transplantation and day 100/day 200 after alloSCT in all cohorts, refGVHD, TMA and both. In contrast, VEGF levels (day 100) were significantly lower specifically in patients with TMA with or without refGVHD, but not in patients with refGVHD without TMA (Table 1).ConclusionsThis study identifies renal TMA as an endothelial cell dysfunction associated with extremely high mortality rates in the context of GVHD. The absence or presence of renal TMA defines two separate subsets of refGVHD with a different prognosis. Biomarkers of endothelial damage or vulnerability, such as sTM, ST2, and VEGF can help to dissect TMA and refGVHD, and might be useful to identify and guide management of patients with endothelial dysfunction who are at high risk of fatal complications after alloSCT.Table 1p=0.000 [Display omitted] Cytokines on days 100 (sTM and VEGF) or day 200 (ST2) in patients with renal TMA, refractory GVHD, or bothMedian (range) in pg/mlTable 1Cytokine/conditionno GVHD no TMATMA onlyrefGVHD onlybothChi2sTM d10011.7 (0-40.0)15.0 (9.1-19.6)14.0 (9.8-31.2)20.4 (12.3-40.0)0.000sST2 d200550.0 (0-20000)1719.8 (143-11968)2268.6 (506-20000)6718.1 (429-20000)0.000VEGF d100111.7 (7,8-753.3)66.1 (42.1-156.6)114.12 (34.9-497.3)74.8 (19.8-576.6)0.035 DisclosuresNo relevant conflicts of interest to declare.

Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy.

Although genetic testing has been recommended in patients with hypertrophic cardiomyopathy (HCM) in current clinical practice, its utility in prognostic prediction remains to be ascertained. We assessed the dosage effect of rare variants in sarcomere genes on the long-term outcomes of HCM. A total of 529 unrelated HCM patients were prospectively recruited and followed for 4.7 ± 3.2 years. Eight sarcomere genes were screened with targeted resequencing and identified variants were validated through Sanger sequencing. After polymorphisms and likely neutral rare variants were excluded, the patients were segregated into three groups based on the dosage of rare variants: no rare variant, a single rare variant, and multiple rare variants. Multiple rare variants were identified in 7.2% (38/529) of the study patients. Patients with multiple rare variants were younger at diagnosis, and had greater maximum LV wall thicknesses and larger left atria. The risk for cardiovascular death in patients with multiple rare variants was higher than in those without rare variants (P =10⁻⁵) or in those with a single rare variant (P = 2 × 10⁻⁵). Multivariable analysis revealed that multiple rare variants were a risk factor for cardiovascular death [hazard ratio (HR) 3.74, 95% confidence interval (CI) 1.84-7.58, P = 0.0003], as well as sudden cardiac death (HR 3.57, 95% CI 1.23-10.35, P = 0.019) and heart failure-related death (HR 4.62, 95% CI 1.67-12.76, P = 0.003). The presence of multiple rare variants in sarcomere genes is a risk factor for malignant outcomes in HCM, and may be appropriate to consider as a criterion in the risk stratification of HCM patients.

Visceral Fat Level Is an Independent Risk Factor for Cardiovascular Mortality in Hemodialysis Patients

Background: Obesity is an independent risk factor for morbidity and mortality in cardiovascular diseases not only in the general population, but also in hemodialysis (HD) patients. We previously reported that an increased visceral fat area (VFA) determined using computed tomography (CT) scans was associated with atherosclerosis in HD patients. However, whether a high VFA is associated with increased cardiovascular mortality in HD patients remains unknown. Therefore, we investigated the relationship between VFA and prognosis in HD patients. Methods: VFA was estimated in 126 patients on maintenance HD using CT scans. These patients were followed for 60 months. Results: Kaplan-Meier analysis revealed that the cardiovascular survival rate was significantly lower in the high-VFA group, with a VFA of 71.5 cm² or greater, than in the low-VFA group, with a VFA of less than 71.5cm². In univariate Cox proportional hazards analyses, age, albumin, low-density lipoprotein cholesterol, cardio-thoracic ratio and VFA above 71.5 cm² were significantly correlated with cardiovascular deaths. In multivariate analyses testing these factors as dependent variables, VFA above 71.5 cm² was estimated to be an independent predictor of cardiovascular deaths. Conclusion: These results suggest that an increased VFA is a stronger risk factor for cardiovascular deaths in HD patients. Measuring VFA may be recommended for predicting the risk of cardiovascular diseases in HD patients.

Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Hemodialysis Patients

Background: Left ventricular hypertrophy (LVH) is a common cardiovascular complication and an independent risk factor for cardiovascular death in hemodialysis (HD) patients. Previous studies have shown that fibroblast growth factor 23 (FGF23), which has an important role in phosphate metabolism, is elevated in HD patients. Objectives: The aim of this study was to determine the association of FGF23 and LVH and the prognostic value of serum FGF23 level in HD patients. One hundred seven HD patients were evaluated for LVH by echocardiography. Serum FGF23 levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Patients with LVH were more likely to have higher systolic blood pressure (BP) and LVH was significantly associated with female gender and higher serum levels of phosphate and calcium ×phosphate products. LVH was also associated with higher serum FGF23 level. Multivariate analysis indicated that serum FGF23 level, systolic BP, and serum phosphate level remained correlated with LVH. This suggested that serum FGF23 level is independently associated with LVH in our HD patients. Cox analysis indicated no significant difference in risk of death for patients with elevated serum FGF23 level. Conclusion: LVH has a high prevalence in HD patients, and FGF23 is independently associated with LVH but is not a predictor for prognosis during a 4-year follow-up period.

Increased Persistent Sodium Current Due to Decreased PI3K Signaling Contributes to QT Prolongation in the Diabetic Heart

Diabetes is an independent risk factor for sudden cardiac death and ventricular arrhythmia complications of acute coronary syndrome. Prolongation of the QT interval on the electrocardiogram is also a risk factor for arrhythmias and sudden death, and the increased prevalence of QT prolongation is an independent risk factor for cardiovascular death in diabetic patients. The pathophysiological mechanisms responsible for this lethal complication are poorly understood. Diabetes is associated with a reduction in phosphoinositide 3-kinase (PI3K) signaling, which regulates the action potential duration (APD) of individual myocytes and thus the QT interval by altering multiple ion currents, including the persistent sodium current INaP. Here, we report a mechanism for diabetes-induced QT prolongation that involves an increase in INaP caused by defective PI3K signaling. Cardiac myocytes of mice with type 1 or type 2 diabetes exhibited an increase in APD that was reversed by expression of constitutively active PI3K or intracellular infusion of phosphatidylinositol 3,4,5-trisphosphate (PIP3), the second messenger produced by PI3K. The diabetic myocytes also showed an increase in INaP that was reversed by activated PI3K or PIP3. The increases in APD and INaP in myocytes translated into QT interval prolongation for both types of diabetic mice. The long QT interval of type 1 diabetic hearts was shortened by insulin treatment ex vivo, and this effect was blocked by a PI3K inhibitor. Treatment of both types of diabetic mouse hearts with an INaP blocker also shortened the QT interval. These results indicate that downregulation of cardiac PI3K signaling in diabetes prolongs the QT interval at least in part by causing an increase in INaP. This mechanism may explain why the diabetic population has an increased risk of life-threatening arrhythmias.

Resistance Artery Creatine Kinase mRNA and Blood Pressure in Humans

Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of high resistance artery creatine kinase-BB rapidly regenerating ATP for vascular contractility. Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human resistance arteries are associated with blood pressure. We isolated resistance-sized arteries from omental fat donated by consecutive women undergoing uterine fibroid surgery. Blood pressure was measured in the sitting position. Vessels of 13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect correlation with diastolic blood pressure (correlation coefficient, 0.9; 95% confidence interval, 0.6-1.0) and were well correlated with systolic blood pressure, with a 90% relative increase in resistance artery creatine kinase B mRNA in hypertensives compared with normotensives, normalized copy numbers were, respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1), P=0.0045. To our knowledge, this is the first direct evidence suggesting that resistance artery creatine kinase mRNA expression levels concur with blood pressure levels, almost doubling with hypertension. These findings add to the evidence that creatine kinase might be involved in the vasculature's pressor responses.

Simultaneous reversal of risk factors for cardiac death and intensified therapy in long-term survivors of paediatric end-stage renal disease over the last 10 years

In an extended long-term follow-up of patients on chronic renal replacement therapy (RRT) since childhood (LERIC study), we observed a substantial reduction in cardiovascular (CV) death over the last decade. In this study, we investigated the contemporaneous changes in risk factors for CV death and cardioprotective therapy. The cohort consisted of 140 Dutch patients, who were born before 1979 and started RRT before 15 years of age between 1972 and 1992. We compared the prevalence of various factors in 2000 and 2010 by calculating matched odds ratios (OR(matched)). Median age of patients was 38.5 years (range 23.2-50.8) in 2010, after a median time on RRT of 28 years. The prevalence of CV risk factors decreased from 41.3% in 2000 to 18.8% in 2010. The OR(matched) in 2010 compared with 2000 for left ventricular hypertrophy, hypertension and hypercholesterolaemia were 0.26 (95% CI 0.09-0.66), 0.22 (95% CI 0.01-0.59) and 0.04 (95% CI 0.01-0.25), respectively. The rate of nonfatal CV events dropped, although not significantly, from 1.75/100 (95% CI 1.3-2.4) per patient year (py) in 1972-2000 to 0.95/100 (95% CI 0.5-1.7) py in 2000-2010. ACE inhibitors/angiotensin receptor blockers and cholesterol lowering medication were prescribed significantly more often in the period 2000-10 [OR(matched) = 7.40 (95% CI 2.90-24.10) and 11.5 (95% CI 4.20-43.90)]. Trends were similar among those who survived and those who did not survive the last decade. We observed a decrease in clinical CV disease synchronous to intensified antihypertensive and antidyslipidaemic therapy in long-term survivors of paediatric renal failure. This advocates a vigorous cardioprotective management in these patients.

Pathogenic factors and prognosis of non cardiac inpatients with acute myocardial infarction

To collect the clinical data of non-cardiac inpatients with coronary heart disease risk factors and analyze the pathogenic factors and prognosis features of these inpatients with acute myocardial infarction. Retrospective analyses were performed for 650 cases of consecutive non-cardiac inpatients with coronary heart disease risk factors at Tianjin Union Medical Center between January 2009 and January 2012.They were divided into non myocardial infarction (UnAMI, n = 551) and myocardial infarction groups (AMI, n = 99). Firstly the method of single factor analysis was employed to screen some significant influencing factors of acute myocardial infarction.Secondly multivariate Logistic regression analysis was performed to analyze the risk factors associated with the onset of AMI. Also the cardiovascular death event rates during hospitalization were compared between two groups. Cox regression analysis was performed to analyze independent risk factors for cardiovascular death of two group during hospitalization. (1) The significant influencing factors of AMI included total cholesterol (TC), low-density lipoprotein (LDL), advanced age, discontinuation of antiplatelet drug, recent episodes of angina above II grade, arrhythmia, 5 years of PCI or CABG history, blood glucose control or not, cardiac dysfunction (NYHA II-IV), dehydration, severe inflammatory response, infection, peroperative period, emergency operation and without cardiological consultation. (2) Multivariate Logistic regression analysis showed that LDL (OR (odds ratio): 2.047, 95% CI (confidence interval): 1.066-3.930, P = 0.031), discontinuation of antiplatelet drug therapy (OR:15.213, 95% CI: 5.746-40.281, P = 0.000), recent episodes of angina above II grade (OR: 1.990, 95%CI: 1.155-3.430, P = 0.013), glucose non-control (OR: 2.991, 95% CI:1.485-6.026, P = 0.002), advanced age (OR: 2.499, 95% CI: 1.299-4.808, P = 0.006), severe inflammation (OR:4.425, 95% CI: 2.984-6.561, P = 0.000), infection (OR:2.405, 95% CI: 1.058-5.464, P = 0.036), emergency operation (OR:4.365, 95% CI: 1.580-12.060, P = 0.004) were all AMI-related occurring factors. And cardiologic consultation (OR: 0.011, 95% CI:0.003-0.040, P = 0.000) was a favorable factors to reduce AMI; (3) AMI group during hospitalization for cardiovascular death event rate was higher than the UnAMI group; (4) Advanced age (β = 0.776, OR = 0.460, 95% CI: 0.217-0.974, P = 0.042) and without consultation of cardiology department (β = 1.366, OR = 3.918, 95% CI: 1.549-9.912, P = 0.004) were cardiovascular death independent risk factors. (1) Non cardiac inpatients during hospitalization LDL, discontinuation antiplatelet drug therapy, recent episodes of angina above II grade, blood sugar non-control, advanced age, severe inflammatory response, infection and without cardiologic consultations were significant risk factors for AMI. (2) The treatment of Department of Cardiology specialist for non cardiac inpatients with coronary heart disease risk factors to improve the prognosis of them.

Cardiovascular Mortality in Obstructive Sleep Apnea in the Elderly: Role of Long-Term Continuous Positive Airway Pressure Treatment

Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in middle-aged subjects, but it is not known whether it is also a risk factor in the elderly. To investigate whether OSA is a risk factor for cardiovascular death and to assess whether continuous positive airway pressure (CPAP) treatment is associated with a change in risk in the elderly. Prospective, observational study of a consecutive cohort of elderly patients (≥65 yr) studied for suspicion of OSA between 1998 and 2007. Patients with an apnea-hypopnea index (AHI) less than 15 were the control group. OSA was defined as mild to moderate (AHI, 15-29) or severe (AHI, ≥30). Patients with OSA were classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). Participants were monitored until December 2009. The end point was cardiovascular death. A multivariate Cox survival analysis was used to determine the independent impact of OSA and CPAP treatment on cardiovascular mortality. A total of 939 elderly were studied (median follow-up, 69 mo). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 2.25 (confidence interval [CI], 1.41 to 3.61) for the untreated severe OSA group, 0.93 (CI, 0.46 to 1.89) for the CPAP-treated group, and 1.38 (CI, 0.73 to 2.64) for the untreated mild to moderate OSA group. Severe OSA not treated with CPAP is associated with cardiovascular death in the elderly, and adequate CPAP treatment may reduce this risk.

Fibroblast growth factor-23 and interleukin-6 are risk factors for left ventricular hypertrophy in peritoneal dialysis patients

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular death in dialysis patients. Fibroblast growth factor-23 (FGF-23) and interleukin-6 (IL-6) were thought to be related to cardiovascular diseases (CVDs) in dialysis. To determine the relationship between FGF-23, IL-6 and LVH in continuous ambulatory peritoneal dialysis (CAPD) patients, serum FGF-23 and IL-6 levels as well as standard laboratory parameters were assessed in 62 CAPD patients and 30 healthy controls. LVH was determined by echocardiography in dialysis patients. Serum FGF-23 and IL-6 levels were significantly higher in CAPD patients than in healthy controls, whereas both were higher in patients with LVH than in patients without LVH. FGF-23 was found to be positively associated with left ventricle mass index (LVMI) and serum phosphate. IL-6 level was positively associated with LVMI and negatively correlated with serum albumin and hemoglobin. Serum FGF-23 level was positively correlated with IL-6 level. FGF-23 and IL-6 are independent risk factors for LVH in CAPD patients and both collaborated in causing LVH in CAPD.

Risk of adverse cardiovascular events (CVE) and incident diabetes mellitus (DM) in patients (pts) with prostate cancer (PC) treated with androgen deprivation therapy (ADT): A meta-analysis of adjusted observational results.

e15192 Background: ADT is a mainstay treatment in pts with PC and is supposedly associated to an unfavorable metabolic and cardiovascular profile. Recently, a meta-analysis of randomized controlled trials (RCT) found no association between ADT and increased risk of CVE (JAMA 2011). However, no conclusive data were available about ADT association with metabolic changes and adverse CVE or DM because of pts selection in RCT. Therefore, we performed a meta-analysis of adjusted observational results in order to look for DM and CVE onset in an ADT unselected population. Methods: Medline, Cochrane Library and Biomed Central were searched for articles addressing adverse events related to ADT in patients with PC. Selection criteria were: not RCT, pts assigned to ADT or not, adjusted risk of CVE and DM according to ADT. Exclusion criteria were: duplicate publication, comparison of two different strategies of ADT (different drugs or duration). Cardiovascular death was the primary endpoint; non-fatal myocardial infarction (MI), stroke/transient ischemic attack (TIA) and new DM onset were secondary endpoints. Random effects model with generic inverse variance weighting was used to estimate adjusted risks as odds ratios (OR) with 99% confidence interval (CI). Results: We selected 12/2100 screened studies. We included 208643 pts of which 102177 received ADT. At a follow up of 5 years (4-7.5), ADT did not result as an independent risk factor for cardiovascular death (OR= 1.04; 99% CI= 0.94-1.14). No increased risk of MI (OR= 1.13; CI= 0.86-1.48) or of stroke/TIA (OR= 1.11; CI= 0.78-1.57) were detected. Incident DM was more frequent among ADT pts (OR= 1.32; CI= 1.14-1-53). Even in 7205 pts with previous CVE (2450 received ADT), ADT was not associated with an increased risk of overall death (OR= 1.23; CI= 0.87-1.75). Meta-regression analysis showed no significant interactions between duration of ADT and cardiovascular death or incident DM. Conclusions: In non-selected pts,ADT appears to increase the risk of incident DM, but not of CVE or stroke/TIA. Moreover, overall mortality is not increased in pts with a history of CVE.

Stress Testing in Patients With Hypertrophic Cardiomyopathy

Exercise echocardiography is an important and useful tool for the evaluation of symptoms and monitoring the response to therapy in patients with hypertrophic cardiomyopathy (HCM). A significant number of patients without resting left ventricular outflow tract gradients develop dynamic obstruction with exercise. Detection of an exercise-induced gradient provides a therapeutic target for the relief of symptoms. Abnormal blood pressure response to exercise is an important, although nonspecific, risk factor for cardiovascular death in patients with HCM. Stress testing such as myocardial perfusion imaging lacks specificity in diagnosing coronary artery disease in patients with HCM but has a good negative predictive value. Exercise stress test in controlled environment seems to be safe in properly selected patients with HCM, and benefits of the diagnostic and prognostic information obtained outweigh the small risks.

Is Obstructive Sleep Apnea Associated with Cardiovascular Mortality in Women

Obstructive sleep apnea (OSA) is a recognized risk factor for cardiovascular death in men but hasn't been well studied in women. To find out more,

Cardiovascular Mortality in Women With Obstructive Sleep Apnea With or Without Continuous Positive Airway Pressure Treatment

Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in men, but whether it is also a risk factor in women is unknown. To investigate whether OSA is a risk factor for cardiovascular death in women and assess whether continuous positive airway pressure (CPAP) treatment is associated with a change in risk. Prospective, observational cohort study. 2 sleep clinics in Spain. All women consecutively referred for suspected OSA between 1998 and 2007. Every woman had a diagnostic sleep study. Women with an apnea-hypopnea index (AHI) less than 10 were the control group. Obstructive sleep apnea was diagnosed when the AHI was 10 or higher (classified as mild to moderate [AHI of 10 to 29] or severe [AHI ≥30]). Patients with OSA were classified as CPAP-treated (adherence ≥4 hours per day) or untreated (adherence <4 hours per day or not prescribed). Participants were followed until December 2009. The end point was cardiovascular death. 1116 women were studied (median follow-up, 72 months [interquartile range, 52 to 88 months]). The control group had a lower cardiovascular mortality rate (0.28 per 100 person-years [95% CI, 0.10 to 0.91]) than the untreated groups with mild to moderate OSA (0.94 per 100 person-years [CI, 0.10 to 2.40]; P = 0.034) or severe OSA (3.71 per 100 person-years [CI, 0.09 to 7.50]; P < 0.001). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 3.50 (CI, 1.23 to 9.98) for the untreated, severe OSA group; 0.55 (CI, 0.17 to 1.74) for the CPAP-treated, severe OSA group; 1.60 (CI, 0.52 to 4.90) for the untreated, mild to moderate OSA group; and 0.19 (CI, 0.02 to 1.67) for the CPAP-treated, mild to moderate OSA group. The study was observational and not randomized, and OSA was diagnosed by 2 different methods. Severe OSA is associated with cardiovascular death in women, and adequate CPAP treatment may reduce this risk. None.

Prevalência e correlatos de doença vascular no exame de ultrassom em pacientes em hemodiálise

Patients on hemodialysis present an increased risk of cardiovascular death. Intimal media thickness (IMT) and presence of arterial calcifications are well-known risk factors for cardiovascular death in hemodialysis patients.To assess the prevalence of IMT and arterial calcifications in HD patients and to correlate image findings with clinical and laboratory data.Cross-sectional study involving 75 patients on dialysis for >12 months. Patients underwent B-mode ultrasound scan (US) for determination of IMT of the distal third of the common carotid arteries. Arterial calcifications were assessed by US of carotids, femoral and tibial arteries, and labeled positive if calcification was found in any arterial site.Patients were 52±13 years old, 57% were males and 16% were diabetics. IMT > 0.9 mm was found in 57% of cases and arterial calcifications at US in 48%. Aging (decades) and smoking were associated with both increased IMT (adjusted odds ratio [aOR] = 3.4, p < 0.001; aOR = 4.4, p = 0.045, respectively) and presence of vascular calcifications (aOR = 3.0, p < 0.001; aOR = 6.8, p = 0.011, respectively). High intact parathyroid hormone levels (per each 100 pg/ml) were significantly associated with increased IMT (aOR = 1.7, p = 0.021), but not with vascular calcification. In contrast, Diabetes and time on dialysis (years) were significant determinants for calcifications at US (aOR = 15.0, p = 0.009; aOR = 1.39, p = 0.020), but not for increased IMT.Increased IMT and calcifications at US are common findings in hemodialysis patients. Aging and smoking are consistent determinants for both image alterations. Parathyroid hormone elevation is associated with increased IMT. Diabetes and time on dialysis substantially increase the risk for arterial calcification.

Common Variation at the 11-β Hydroxysteroid Dehydrogenase Type 1 Gene Is Associated With Left Ventricular Mass

Polymorphisms in 11-β hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) have been reported to be associated with obesity-related cardiovascular risk factors, such as type II diabetes and hypertension. Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular death associated with these factors but has significant additional heritability, the cause of which is undetermined. The 11β-HSD1 is believed to maintain tonic inhibition of the mineralocorticoid receptor in cardiomyocytes, and mineralocorticoid receptor activation is involved in the pathophysiology of LVH. We assessed the association between polymorphisms in the HSD11B1 gene and left ventricular mass (LVM) in 248 families ascertained through a proband with hypertension. LVM was measured by electrocardiography and echocardiography in 868 and 829 participants, respectively. Single-nucleotide polymorphisms (SNPs) tagging common variation in the HSD11B1 gene were genotyped by mass spectrometry. The rs846910 SNP, which lies in the flanking region 5' to exon 1B of HSD11B1, was associated with LVM both by electrocardiography (≈5% lower LVM per copy of the rare allele, P=0.02) and by echocardiography (≈10% lower LVM per copy of the rare allele, P=0.003). Genotype explained 1% to 2% of the population variability in LVM, or approximately 5% of the heritable fraction. There were no significant associations between any HSD11B1 SNP and blood pressure or body mass index that could have confounded the association with LVM. Genotype at HSD11B1 has a small, but significant effect on LVM, apparently independently of any effect on obesity-related traits. These findings suggest a novel action of 11β-HSD1 in the human cardiomyocyte, which may be of therapeutic importance.