Higher Risk Of Cardiovascular Death Research Articles

Abstract 12660: Model of End-Stage Liver Disease Excluding INR (MELD-XI) Scoring System Provides the Long-Term Prognostic Information in Patients Admitted With Acute Decompensated Heart Failure, Regardless of Reduced or Preserve Left Ventricular Ejection Fraction

Backgrounds: Liver dysfunction has a prognostic impact on the outcome of patients with advanced heart failure. A model of end-stage liver disease excluding INR (MELD-XI) is a robust scoring system of liver dysfunction, and a high score has been shown to be associated with poor prognosis in patients with heart failure. However, there is little information available on the long-term prognostic significance of MELD-XI score in patients admitted with acute decompensated heart failure (ADHF), relating to reduced or preserved left ventricular ejection fraction (HFrEF or HFpEF). Methods and Results: We studied 303 consecutive patients admitted with ADHF and discharged with survival (HFrEF(LVEF<50%); n=163, HFpEF;n=140). MELD-XI score was calculated by the following formula: 5.11[[Unable to Display Character: ･]]ln(bilirubin)+11.79[[Unable to Display Character: ･]]ln(creatinine)+9.44. During a follow-up period of 5.0±4.3 yrs, 75 patients had cardiovascular death (CVD). Receiver-operator curve analysis revealed that MELD-XI score of 12 was a fair discriminator for CVD (AUC 0.704 (95%CI 0.635-0.772), p<0.0001; sensitivity 67% and specificity 62%). In HFrEF group, MELD-XI score was significantly independently associated with CVD (p=0.0037) at multivariate Cox analysis, and patients with high MELD-XI score (≥12) had a higher risk of CVD than those with low MELD score (46% vs 24%, p=0.0038, hazard ratio: 2.20 (95%CI 1.27-3.79)). In HFpEF group, MELD-XI score was also significantly independently associated with CVD (p=0.005) at multivariate Cox analysis, and patients with high MELD-XI score (≥12) had a higher risk of CVD (34% vs 8%, p<0.0001, hazard ratio: 6.25 (95%CI 2.59-15.05)). Conclusion: A MELD-XI scoring system would provide the long-term prognostic information in patients admitted with ADHF, regardless of HFrEF or HFpEF.

Abstract 17312: Amyloid-β (1-40) and the Risk of Death from Cardiovascular Causes in Patients with Coronary Heart Disease

Introduction: Investigation of the clinical value of biologic pathways that are involved in pathogenesis of atherosclerotic disease is essential for identification of novel therapeutic targets and improvement of cardiovascular risk stratification. Hypothesis: To determine the clinical value of amyloid-β 1-40 (Aβ40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects. Methods: Aβ40 was retrospectively measured in blood samples collected from three independent prospective cohorts and two case-control cohorts (total n=1464). Major adverse CV events (MACE) were assessed in the two prospective cohorts (n=877) followed for a median of 4.4 years. Arterial stiffness was evaluated at baseline and after a 5-year follow-up period (n=107) in young healthy subjects. The primary endpoint was the predictive value of Aβ40 for CV mortality and outcomes in patients with CHD. Further, the associations of Aβ40 levels with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD were addressed. Results: In Cox proportional-hazards models adjusted for age, gender, glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein and high-sensitivity troponin-T, Aβ40 was an independent predictor of CV death and MACE in patients with CHD (P<0.05 for all). After multivariate adjustment, Aβ40 levels conferred a substantial enhancement of net reclassification index (continuous NRI value and 95% confidence interval: 36.7%, 12.5-60.7, P=0.001) and integrated discrimination improvement (IDI value±SE: 1.92±0.62, P<0.001) of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Aβ40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD. Conclusions: Measuring blood levels of Aβ40 identifies patients at high risk for cardiovascular death.

Global platelet hyperreactivity and elevated C-reactive protein levels predict long term mortality in STEMI patients

BackgroundData on long term - more than 1-year - prognostic value of global platelet reactivity (G-HPR) – by adenosine diphosphate (ADP) and arachidonic acid (AA) - in patients with STEMI undergoing PCI are limited. High C-reactive protein (CRP) levels have been suggested to be associated with post-PCI atherothrombotic events. Our aim was to evaluate the long-term prognostic impact of G-HPR and CRP levels in STEMI patients. Methods and ResultsWe evaluated 494 STEMI patients (366M/128F; age: 65.8±12.4yrs) undergoing PCI with stent implantation. At a median follow-up of 2.3years (1.09-4.06), in 58 patients we documented cardiovascular death (11.7%). Platelet reactivity was assessed by light transmission aggregometry by 1mM AA (AA-LTA) and 10 microM ADP (ADP-LTA). By the ROC curve analysis, 17%, 52% and 12mg/L were found to be the values of AA-LTA, ADP-LTA and CRP associated with the highest specificity and sensitivity for death. G-HPR was defined as the presence of both AA-LTA ≥17% and ADP-LTA ≥52%. At Cox regression analysis adjusted for age, sex, cardiovascular risk factors, multivessel disease, ejection fraction, renal insufficiency, G-HPR and elevated CRP levels were associated with long-term mortality [HR=1.78 (95%CI 1.04-3.03), p=0.036 and HR=2.91 (1.54-5.52, p=0.001), respectively]. The contemporary presence of G-HPR and elevated CRP levels was associated with the highest risk of death [HR=5.1 (95%CI 1.9-13.4), p=0.001]. ConclusionG-HPR and CRP are independent long-term prognostic markers in STEMI patients. The contemporary presence of G-HPR and CRP identifies a subgroup of patients at significantly higher risk of cardiovascular death.

ECG Morphological Variability in Beat Space for Risk Stratification After Acute Coronary Syndrome

BackgroundIdentification of patients who are at high risk of adverse cardiovascular events after an acute coronary syndrome (ACS) remains a major challenge in clinical cardiology. We hypothesized that quantifying variability in electrocardiogram (ECG) morphology may improve risk stratification post‐ACS.Methods and ResultsWe developed a new metric to quantify beat‐to‐beat morphologic changes in the ECG: morphologic variability in beat space (MVB), and compared our metric to published ECG metrics (heart rate variability [HRV], deceleration capacity [DC], T‐wave alternans, heart rate turbulence, and severe autonomic failure). We tested the ability of these metrics to identify patients at high risk of cardiovascular death (CVD) using 1082 patients (1‐year CVD rate, 4.5%) from the MERLIN‐TIMI 36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non‐ST‐Elevation Acute Coronary Syndrome—Thrombolysis in Myocardial Infarction 36) clinical trial. DC, HRV/low frequency–high frequency, and MVB were all associated with CVD (hazard ratios [HRs] from 2.1 to 2.3 [P<0.05 for all] after adjusting for the TIMI risk score [TRS], left ventricular ejection fraction [LVEF], and B‐type natriuretic peptide [BNP]). In a cohort with low‐to‐moderate TRS (N=864; 1‐year CVD rate, 2.7%), only MVB was significantly associated with CVD (HR, 3.0; P=0.01, after adjusting for LVEF and BNP).ConclusionsECG morphological variability in beat space contains prognostic information complementary to the clinical variables, LVEF and BNP, in patients with low‐to‐moderate TRS. ECG metrics could help to risk stratify patients who might not otherwise be considered at high risk of CVD post‐ACS.

Coronary artery disease severity and aortic stenosis: clinical outcomes according to SYNTAX score in patients undergoing transcatheter aortic valve implantation

The aim of this study was to evaluate whether coronary artery disease (CAD) severity exerts a gradient of risk in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). A total of 445 patients with severe AS undergoing TAVI were included into a prospective registry between 2007 and 2012. The preoperative SYNTAX score (SS) was determined from baseline coronary angiograms. In case of revascularization prior to TAVI, residual SS (rSS) was also determined. Clinical outcomes were compared between patients without CAD (n = 158), patients with low SS (0-22, n = 207), and patients with high SS (SS > 22, n = 80). The pre-specified primary endpoint was the composite of cardiovascular death, stroke, or myocardial infarction (MI). At 1 year, CAD severity was associated with higher rates of the primary endpoint (no CAD: 12.5%, low SS: 16.1%, high SS: 29.6%; P = 0.016). This was driven by differences in cardiovascular mortality (no CAD: 8.6%, low SS: 13.6%, high SS: 20.4%; P = 0.029), whereas the risk of stroke (no CAD: 5.1%, low SS: 3.3%, high SS: 6.7%; P = 0.79) and MI (no CAD: 1.5%, low SS: 1.1%, high SS: 4.0%; P = 0.54) was similar across the three groups. Patients with high SS received less complete revascularization as indicated by a higher rSS (21.2 ± 12.0 vs. 4.0 ± 4.4, P < 0.001) compared with patients with low SS. High rSS tertile (> 14) was associated with higher rates of the primary endpoint at 1 year (no CAD:12.5%, low rSS: 16.5%, high rSS: 26.3%, P = 0.043). Severity of CAD appears to be associated with impaired clinical outcomes at 1 year after TAVI. Patients with SS > 22 receive less complete revascularization and have a higher risk of cardiovascular death, stroke, or MI than patients without CAD or low SS.

A Combinational Therapy for Patients with Severe Psoriasis Associated with Cardiovascular Disease

Psoriasis a chronic inflammatory disease of skin often involving the joints associated with concomitant factors like cardiovascular involvement, leading to high mortality.Hence, we designed the study to know the effect of combinational therapy and the associated risks of cardiovascular disease (CVD) in psoriasis patients.120 psoriasis patients and 50 healthy individuals of both sexes between 25-65 years of age with severe psoriasis attending Chinese hospital during October 2009-November 2013 were included in the study. Patients were treated with methotrexate, acitretin, cyclosporine and also with combination therapy.Patients experienced a reduced degree of lesions with combination therapy with 40% reduction or had complete normalization of the skin. Severe psoriasis patients are at high risk of mortality due to CVD with hazard ratio (HR) 1 · 57, 95% confidence interval (CI) 1 · 26-1 ·96.Severe psoriasis is often associated with higher risk of cardiovascular death. A large scale prospective study is required for analyzing risk factors of CVD in psoriasis (PsA).

Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort

ObjectivesUrinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death. MethodsThe association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes. ResultsHigh u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2–5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7–36, P < 0.001, compared to all three biomarkers normal). ConclusionsThis study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.

Clinical Implications and Correlates of Q Waves in Patients With ST‐Elevation Myocardial Infarction Treated With Fibrinolysis: Observations from the CLARITY‐TIMI 28 Trial

The relationships between Q waves that appear during the acute phase of ST-elevation myocardial infarction (STEMI), clinical characteristics, ST-segment resolution (STRes), and clopidogrel therapy in patients treated with fibrinolysis are not well described. We hypothesized that Q waves would be associated with less successful reperfusion and increased cardiovascular events. In the CLARITY-TIMI 28 trial, 3491 STEMI patients treated with fibrinolysis were randomized to clopidogrel or placebo. Electrocardiograms were evaluated for STRes post-fibrinolysis and the presence of pathologic Q waves during the index hospitalization in 3322 patients. Q waves were identified in 2045 patients (61.6%) prior to discharge and were associated with increased odds of congestive heart failure (CHF) (adjusted odds ratio [ORadj ]: 2.10, P = 0.002) or the composite of cardiovascular death/CHF at 30 days (ORadj : 2.08, P ≤ 0.001). Q waves were associated with lower odds of Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 to 3 (ORadj : 0.78, P = 0.028), TIMI myocardial perfusion grade 3 (ORadj : 0.83, P = 0.029), and complete STRes at 90 minutes (ORadj : 0.80, P = 0.030). Patients with both a Q wave and incomplete STRes 90 minutes after fibrinolysis were at higher risk for cardiovascular death or CHF (11.1%) than patients with no Q wave and at least partial STRes (1.9%). Overall, clopidogrel tended to be equally or more effective in patients without Q waves compared to those with Q waves. Among STEMI patients treated with fibrinolysis, evaluating for Q waves prior to discharge is a simple method of assessing for less successful reperfusion and an increased risk of adverse 30-day cardiovascular outcomes. The combination of Q waves and 90-minute STRes allows additional risk refinement.

Diastolic blood pressure, aortic atheroma, and prognosis in hypertension: New insights into a complex association

ObjectivesOur study aimed at determining the interaction between the prognostic value of diastolic blood pressure (DBP) and aortic atherosclerosis (ATS). BackgroundWith aging, equal systolic blood pressures (SBPs) become associated with low DBPs; i.e., high pulse pressures (PPs) become associated with a high risk of cardiovascular death. This association is usually ascribed to aortic stiffening with age but the precise impact of low DBP per se is yet uncertain. Methods938 hypertensive patients recruited in the seventies had an aortic ATS score at pretreatment aortography. All-cause and cardiovascular deaths were assessed 20 years later. The prognostic values of DBP and SBP were assessed by a multivariate Cox regression model and their interactions with ATS examined. ResultsIn the presence of ATS, an increase of 10 mmHg in DBP was associated with a protective effect: hazard ratios 0.84 [0.72–0.99] for cardiovascular death and 0.88 [0.78–1.00] for all-cause death. However, in the absence of ATS, DBP had no prognostic value: hazard ratios 1.05 [0.89–1.23] for cardiovascular death and 0.99 [0.88–1.11] for all-cause death (p for interaction: 0.061 and 0.087, respectively). No interaction was found between SBP and ATS (p for interaction > 0.40). ConclusionsThe prognostic values of DBP and aortic atheroma are not superimposable; yet, they are tightly connected: a low DBP is disadvantageous only in the presence of a pathologic aorta. Aortic atherosclerosis may explain, at least partly, in some high risk populations, the J-shape of the already reported DBP-outcome relationship.

SOCIO-ECONOMIC RISK FACTORS FOR CARDIOVASCULAR DEATH: DATA FROM 12-YEAR PROSPECTIVE EPIDEMIOLOGIC STUDY

Aim. Studying of the influence of socio-economic risk factors on relative risk (RR) of death from cardiovascular diseases (CVD) in non-organized population of Tyumen city. Material and methods. The epidemiological study was performed with standard approaches on relevant selection of Tyumen citizens aged 25-64 y. During next 12 years the whole cohort (795 men, 814 women) was analyzed for the deaths from cardiovascular diseases (CVD). Multivariate regression model of proportional Kox risk used to estimate RR for cardiovascular death. RR with 95% CI calculated with added concomitant RF like: age, SBP and DBP, BMI, total cholesterol, triglycerides, HDL, smoking state, coronary heart disease anamnesis and arterial hypertension. Results. By 12 years of observation there were 85 (10,7%) cases of cardiovascular death in men and 33 (4,1%) in women. Higher risk of cardiovascular death was in men with low educational level than in those with higher education (RR: 1,94, 95% CI 1,12-3,34). In women the same (RR: 3,42, 95% CI 1,53-7,64) in comparison to more educated women. After standartization of all concomitant factors the risk of cardiovascular death was significantly higher in men and women involved in hard physical labour (RR: 2,51, 95% CI 1,03-6,08 and 5,47, 95% CI 1,69-17,74, resp.), comparing to those of higher labour qualification (RR: 4,08 (95% CI 2,12-7,8), RR 3,19 (95% CI 1,22-8,34) and RR 3,18 (95% CI 1,90-5,34), resp. In women the relation was opposite: RR for cardiovascular death was higher for married women (3,21, 95% CI 1,28-8,06; p<0,001), than for single. Conclusion. The highest risk for cardiovascular death in non-organized Tyumen citizen cohort was found for those with lower educational level, involved into hard physical labour and single, divorced or widowed men. In women, opposite, being married was associated with higher risk of death from CVD.

Cardiovascular morbidity–mortality associated to ankle-brachial index in the general population

Background and objectivesAbnormal ankle-brachial index (ABI) is associated with a high risk of cardiovascular disease. This study has aimed to investigate the association between low ABI and risk of cardiovascular death in a general population attended in a primary care center. Patients and methodsA total of 1361 volunteers aged between 60 and 79 years without any evidence of peripheral artery disease who attended a primary care center participated in the study. They underwent a complete physical examination, together with standard blood tests and ABI was determined. The participants were contacted by telephone 4 years later and asked about any cardiovascular problems for that period. Causes of death and hospitalization were confirmed in the medical records in the primary care center and/or hospital. ResultsInformation was obtained about the clinical evolution of 1300 participants (mean age 69.9 years, 38.2% men). Mean follow-up was 49.8 months. There were 13 cardiovascular death and 49 major cardiovascular events. Low ABI (<0.9) was associated with a significant higher risk of cardiovascular death (adjusted relative risk 6.83; 95% confidence interval 1.36–34.30, P=0.020), and with a higher risk of major cardiovascular events (adjusted relative risk 2.42; 95% confidence interval 0.99–5.91, P=0.051). High or uncompressible ABI was not associated with higher cardiovascular risk. ConclusionsA low ABI was associated with higher risk of cardiovascular death in the general population followed up in a primary care center.

Interaction between baseline and early worsening of renal function and efficacy of renin–angiotensin–aldosterone system blockade in patients with heart failure: insights from the Val‐HeFT study

We evaluated the effect of (dual) renin-angiotensin-aldosterone system (RAAS) blockade with valsartan and an ACE inhibitor [92.7% of patients were treated with an ACE inhibitor in the Valsartan in Heart Failure Trial (Val-HeFT)] in patients with NYHA class II-IV heart failure (HF) and reduced EF on cardiovascular (CV) death and HF hospitalization by subgroups and by presence of early worsening of renal function (EWRF) and according to baseline estimated glomerular filtration rate (eGFR). We analysed the data from 5010 patients enrolled in the Val-HeFT study. A total of 2346 (46.8%) patients had baseline renal impairment (i.e. baseline eGFR <60 mL/min/1.73 m(2)). Further, 425 patients (8.6%) had EWRF (i.e. eGFR decrease >20% within 1 month after randomization), whereas 4503 patients (91.4%) had ≤20% decline in eGFR. Overall, the difference between valsartan and placebo on the composite endpoint of CV death and HF hospitalization was significant [P = 0.0005; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.75-0.92)]. In patients with baseline renal impairment, the difference between the treatment groups was also significant (P = 0.0002; HR 0.76, 95% CI 0.66-0.88). Patients with EWRF had higher risk of CV death and HF hospitalization vs. those without ERWF (P < 0.0001; HR 1.44, 95% CI 1.21-1.71), and within the EWRF group a significant difference was also observed between valsartan and placebo (P = 0.0086; HR 0.63, 95% CI 0.45-0.89). However, the interaction between treatment and eGFR at Month 1 was not significant (P = 0.1160). Benefits were maintained in patients with renal dysfunction at baseline and those who experienced EWRF.

Value of proBNP1–108 testing for the risk stratification of patients with systolic heart failure

The study objectives were to determine the circulating levels of proBNP1–108, the precursor of B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP), in patients with systolic heart failure (HF) and to assess their prognosis value for cardiovascular (CV) death over a long-term follow-up. Seventy-three patients with systolic HF and 68 healthy volunteers were included. ProBNP1–108, BNP and NT-proBNP levels were measured with automated immunoassays and their predictive value for long-term survival was assessed through an 8 years follow-up. ProBNP1–108 levels were markedly increased in patients with systolic HF in comparison to healthy volunteers. In univariate proportional hazard model, survival was related to proBNP1–108, BNP, NT-proBNP, age, EF and glomerular filtration rate (eGFR). Kaplan–Meier survival curves according to proBNP tertiles diverged significantly, and the highest proBNP levels were related to patients with the highest risk of CV death. In a multivariate analysis including age, EF, proBNP1–108, BNP, NT-proBNP, and eGFR levels, NT-proBNP was the strongest predictor of long term CV death. Our study therefore demonstrated that high levels of proBNP1–108, measured with an assay with enhanced analytical specificity, are related to the long-term risk of cardiovascular death in systolic heart failure.

Morbimortalidad cardiovascular asociada al índice tobillo-brazo en la población general

Background and objectivesAbnormal ankle-brachial index (ABI) is associated with a high risk of cardiovascular disease. This study has aimed to investigate the association between low ABI and risk of cardiovascular death in a general population attended in a primary care center. Patients and methodsA total of 1,361 volunteers aged between 60 and 79 years without any evidence of peripheral artery disease who attended a primary care center participated in the study. They underwent a complete physical examination, together with standard blood tests and ABI was determined. The participants were contacted by telephone 4 years later and asked about any cardiovascular problems for that period. Causes of death and hospitalization were confirmed in the medical records in the primary care center and/or hospital. ResultsInformation was obtained about the clinical evolution of 1,300 participants (mean age 69.9 years, 38.2% men). Mean follow-up was 49.8 months. There were 13 cardiovascular death and 49 major cardiovascular events. Low ABI (<0.9) was associated with a significant higher risk of cardiovascular death (adjusted relative risk 6.83; 95% confidence interval 1.36-34.30, P=.020), and with a higher risk of major cardiovascular events (adjusted relative risk 2.42; 95% confidence interval 0.99-5.91, P=.051). High or uncompressible ABI was not associated with higher cardiovascular risk. ConclusionsA low ABI was associated with higher risk of cardiovascular death in the general population followed-up in a primary care center.

Impact of osteoporosis and bone fracture on health-related quality of life in postmenopausal women

Background Osteoporosis is responsible for fragility fractures, which are associated with decreased physical and social function. The GINERISK study was a cross-sectional epidemiological study conducted in 4157 Spanish postmenopausal women initially diagnosed with osteoporosis according to WHO criteria within the last 2 years.Aim The aim of the study was to explore the impact of osteoporosis on health-related quality of life (HRQoL).Method Menopause-specific and generic HRQoL were assessed, respectively, with the specific Cervantes Scale and the generic SF-12v2 Health Survey. The impact of osteoporosis on HRQoL was ultimately evaluated in 3328 (80.1%) women who had measurements for both bone mineral densitometry (BMD) and HRQoL.Results Menopause-specific or generic HRQoL, respectively, were worse in women with current osteoporosis and prior osteoporotic bone fracture (BF) in comparison with current osteoporosis without BF or whose T-score had increased above −2.5 on the BMD after receiving osteoporosis drug therapy. Impaired HRQoL was found both in Spanish postmenopausal female populations and the Spanish general female population. Women with osteoporosis with BF had physical and mental summary component scores in the 20th and 30th percentiles, respectively, of the Spanish general population. Higher risk for cardiovascular death was also associated with greater HRQoL impairment. The use of selective estrogen receptor modulators in women with a BMD T-score ≤ −2.5 was associated with lower impact of osteoporosis on HRQoL, particularly in the domains of physical health and sexuality.Conclusion The HRQoL analysis results in this study demonstrated a loss of quality of life in postmenopausal women with osteoporosis and confirmed that this loss is greater in women with prior osteoporotic fracture.

Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis

Visit-to-visit blood pressure variation (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO Study). We used the coefficient of variation (CV) and the average real variability (ARV) in systolic blood pressure (SBP) as metrics of VTV-BPV. 1844 of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range [IQR] 1.3 to 4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9% ± 4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend towards higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.

Abstract P314: Moderate to Severe Thinness was Strongly Associated with High Risks of Cardiovascular and Infectious Disease-related Death and Incident Stroke Among Japanese Hemodialysis Patients

Background: Overweight and obese is shown to be associated with a high risk for cardiovascular morbidity and mortality in the general population. While, inverse relationship between body mass index (BMI) and a risk for all-cause death was observed in dialysis patients. Thinner dialysis patients are supposed to be a high risk population. However, whether cardiovascular death contributes to a high risk for all-cause mortality or whether non-cardiovascular death contributes to a high risk for all-cause mortality in thinner dialysis patients has not been fully elucidated. Methods: A population-based prospective study of adult hemodialysis patients was carried out. A total of 1209 male and female hemodialysis patients were enrolled and divided into four groups according to BMI (G1: BMI &lt; 17.0; G2: 17.0 ≤ BMI &lt; 18.5; G3: 18.5 ≤ BMI &lt; 25.0; G4: BMI ≥ 25.0 kg/ m 2 ). Main outcomes were all-cause death (ACD), cardiovascular death (CVD), infectious disease-related death (IFD), malignant disease-related death (MAD), incident acute myocardial infarction (AMI) and stroke. Sex- and age-adjusted mortality and incidence rates were estimated in the groups using Poisson’s regression analysis. Results: A total of 453 patients died during the 5 year observation period (4,790 person-years). Overweight (BMI ≥ 25.0 kg/ m 2 ) was not associated with a high risk for ACD, CVD, IFD, MAD, AMI and stroke, while moderate to severe thinness was strongly associated with excessive risks of ACD, CVD, IFD and stroke. Associations between BMI and risks for MAD and AMI were not observed (see table). Conclusion: Skinny hemodialysis patients are supposed to be a high risk population for infectious disease-related and stroke-related death and the findings should be known to hemodialysis patients and their caretakers.

Baseline White Blood Cell Count Is an Independent Predictor of Long-Term Cardiovascular Mortality in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome, but It Does Not Improve the Risk Classification of the GRACE Score

Objectives: To investigate the prognostic significance of baseline white blood cell count (WBCc) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and its additive predictive value beyond the Global Registry of Acute Coronary Events (GRACE) score. Methods: We included 1,315 consecutive NSTE-ACS patients. Patients were divided in quartiles according to the WBCc (cells per 1 mm³) i.e. Q1 <6,850, Q2 = 6,850–8,539, Q3 = 8,540–10,857 and Q4 ≥10,858. The study end point was 3-year cardiovascular death (CVD). Results: The median age of the study population was 76 years. Overall, 335 patients (25.5%) died with 211 of these (16%) suffering from CVD. Patients in Q4 showed a higher cumulative probability of CVD compared to patients in Q1–Q3. On multivariable analysis, patients in Q4 were at higher risk of CVD [hazard ratio (HR) = 1.47, 95% confidence interval (CI) 1.09–1.98, p = 0.011]. WBCc as a continuous variable was also independently associated with the study end point (HR = 1.043; 95% CI 1.02–1.07; p = 0.001). However, the incorporation of WBCc into the GRACE score did not improve either prediction of risk (C-index = 0.796 for GRACE score with or without WBCc) or classification of risk [relative integrated discrimination improvement = 0.0154, 95% CI) –0.029 to 0.0618; continuous net reclassification improvement = –0.0676, 95% CI –0.2149–0.0738). Conclusions: WBCc was an independent predictor of 3-year CVD in patients with NSTE-ACS. However, it did not add prognostic information beyond the GRACE score.

Measuring Platelet Reactivity after Clopidogrel-Has it Reached the End of the Road?

Clopidogrel is traditionally prescribed at 75 mg daily after a 300 mg loading dose. It is a pro-drug, with a two-step activation process involving a series of cytochrome P-450 (CYP) isoenzymes. Its antiplatelet effect is variable and susceptible to genetic polymorphisms. In particular, patients with either 1 or 2 loss-of-function CYP2C19 alleles have an attenuated pharmacologic response and worse clinical outcomes with standard dose clopidogrel [1]. Among clopidogrel-treated subjects in TRITON–TIMI 38, carriers had higher risk of cardiovascular death, myocardial infarction, or stroke as compared with non-carriers (12.1% vs. 8.0%; P=0.01) and higher risk of stent thrombosis (2.6% vs. 0.8%; p=0.02) [1]. Also, the common polymorphisms in the CYP2C19 gene, seen in approximately 30% of whites, may be more common in other ethnic groups -40% of blacks and >55% of East Asians [2].

Ambulatory ECG-based T-wave alternans and heart rate turbulence can predict cardiac mortality in patients with myocardial infarction with or without diabetes mellitus

BackgroundMany patients who survive a myocardial infarction (MI) remain at risk of sudden cardiac death despite revascularization and optimal medical treatment. We used the modified moving average (MMA) method to assess the utility of T-wave alternans (TWA) and heart rate turbulence (HRT) as risk markers in MI patients with or without diabetes mellitus (DM).MethodsWe prospectively enrolled 248 consecutive patients: 96 with MI (post-MI patients); 77 MI with DM (post-MI + DM patients); 75 controls without cardiovascular disease (group control). Both TWA and HRT were measured on ambulatory electrocardiograms (AECGs). HRT was assessed by two parameters ─ turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO ≥0% and TS ≤2.5 ms/R-R interval were met. The endpoint was cardiac mortality. ResultsTWA values differed significantly between MI and controls. Post-MI + DM patients had higher TWA values than post-MI patients (58 ± 21 μV VS 52 ± 18 μV, P = 0.029). Impaired HRT--increased TO and decreased TS were observed in MI patients with or without DM. During follow-up of 578 ± 146 days, cardiac death occurred in ten patients and three of them suffered sudden cardiac death (SCD). Multivariate analysis determined that a HRT-positive outcome [HR (95% CI): 5.01, 1.33–18.85; P = 0.017], as well as the combination of abnormal TWA (≥47 μV) and positive HRT had significant association with the endpoint [HR (95% CI): 9.08, 2.21–37.2; P = 0.002)].ConclusionThis study indicates that AECGs-based TWA and HRT can predict cardiac mortality in MI patients with or without DM. Combined analysis TWA and HRT may be a convenient and useful method of identifying patients at high risk for cardiovascular death.