Angiotensin II Receptor Blocker-based Therapy in Japanese Elderly, High-risk, Hypertensive Patients

BackgroundIt is unknown whether high-dose angiotensin II receptor blocker therapy or angiotensin II receptor blocker + calcium channel blocker combination therapy is better in elderly hypertensive patients with high cardiovascular risk. The objective of the study was to compare the efficacy of these treatments in elderly, high-risk Japanese hypertensive patients.MethodsThe OlmeSartan and Calcium Antagonists Randomized (OSCAR) study was a multicenter, prospective, randomized, open-label, blinded-end point study of 1164 hypertensive patients aged 65 to 84 years with type 2 diabetes or cardiovascular disease. Patients with uncontrolled hypertension during treatment with olmesartan 20 mg/d were randomly assigned to receive 40 mg/d olmesartan (high-dose angiotensin II receptor blocker) or a calcium channel blocker + 20 mg/d olmesartan (angiotensin II receptor blocker + calcium channel blocker). The primary end point was a composite of cardiovascular events and noncardiovascular death.ResultsDuring a 3-year follow-up, blood pressure was significantly lower in the angiotensin II receptor blocker + calcium channel blocker group than in the high-dose angiotensin II receptor blocker group. Mean blood pressure at 36 months was 135.0/74.3 mm Hg in the high-dose angiotensin II receptor blocker group and 132.6/72.6 mm Hg in the angiotensin II receptor blocker + calcium channel blocker group. More primary end points occurred in the high-dose angiotensin II receptor blocker group than in the angiotensin II receptor blocker + calcium channel blocker group (58 vs 48 events, hazard ratio [HR], 1.31, 95% confidence interval, 0.89-1.92; P = .17). In patients with cardiovascular disease at baseline, more primary events occurred in the high-dose angiotensin II receptor blocker group (HR, 1.63, P = .03); in contrast, fewer events were observed in the subgroup without cardiovascular disease (HR, 0.52, P = .14). This treatment-by-subgroup interaction was significant (P = .02).ConclusionThe angiotensin II receptor blocker and calcium channel blocker combination lowered blood pressure more than the high-dose angiotensin II receptor blocker and reduced the incidence of primary end points more than the high-dose angiotensin II receptor blocker in patients with cardiovascular disease. The addition of a second antihypertensive agent is more effective at lowering blood pressure than simply doubling the dose of an existing agent.     

Which leukocyte subsets predict cardiovascular mortality? From the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study

ObjectiveWhite blood cells are known to predict cardiovascular mortality, but form a highly heterogeneous population. It is therefore possible that specific subtypes disproportionally contribute to the prediction of cardiovascular outcomes. Therefore, we compared leukocyte subsets alone and in conjunction with an established inflammatory marker, C-reactive protein, for predicting death due to cardiovascular disease in a high-risk population.MethodsPatients, 3316, (mean [SD] age, 62 [10] years) scheduled for coronary angiography were prospectively followed up. Neutrophil, monocyte and lymphocyte counts were determined. Neutrophil and monocyte subsets were further analysed on the basis of surface expression of CD11b, CD18, CD31, CD40 and CD58. Lymphocytes were further subdivided into CD3, CD4, CD8, and CD19 subsets. The association between each marker and subsequent cardiovascular mortality was assessed using multivariable Cox regression models.ResultsDuring a median follow-up period of 7.8 years, 745 (22.5%) patients died, of which 484 were due to cardiovascular events. After entering conventional risk factors and removing patients with a current infection, neutrophil count (HR [95% CI] = 1.90 [1.39, 2.60], P < 0.001) and the neutrophil/lymphocyte ratio (HR [95% CI] = 1.68 [1.24, 2.27], P = 0.003) emerged as independent predictors of cardiovascular mortality. After mutual adjustment, neutrophil count (HR [95% CI] = 1.87 [1.35, 2.50], P < 0.001) out-performed C-reactive protein (HR [95% CI] 1.32 [0.99, 1.78], P = 0.06) as a predictor of cardiovascular mortality.ConclusionsDue to its predictive potential and inexpensive determination, assessment of high neutrophil counts may represent an important marker, possibly improving cardiovascular mortality risk prediction.     

Hypoglycemia-associated mortality is not drug-associated but linked to comorbidities

ObjectiveAlthough tight glucose control is used widely in hospitalized patients, there is concern that medication-induced hypoglycemia may worsen patient outcomes. We sought to determine if the mortality risk associated with hypoglycemia in hospitalized noncritically ill patients is linked to glucose-lowering medications (drug-associated hypoglycemia) or merely an association mediated by comorbidities (spontaneous hypoglycemia).MethodsA retrospective cohort of patients admitted to the general wards of an academic center during 2007 was studied. The in-hospital mortality risk of a hypoglycemic group (at least 1 blood glucose ≤ 70 mg/dL) was compared with that of a normoglycemic group using survival analysis. Stratification by subgroups of patients with spontaneous and drug-associated hypoglycemia was performed.ResultsAmong 31,970 patients, 3349 (10.5%) had at least 1 episode of hypoglycemia. Patients with hypoglycemia were older, had more comorbidities, and received more antidiabetic agents. Hypoglycemia was associated with increased in-hospital mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.33-2.09; P < .001). However, this greater risk was limited to patients with spontaneous hypoglycemia (HR, 2.62; 95% CI, 1.97-3.47; P < .001) and not to patients with drug-associated hypoglycemia (HR, 1.06; 95% CI, 0.74-1.52; P = .749). After adjustment for patient comorbidities, the association between spontaneous hypoglycemia and mortality was eliminated (HR, 1.11; 95% CI, 0.76-1.64; P = .582).ConclusionDrug-associated hypoglycemia was not associated with increased mortality risk in patients admitted to the general wards. The association between spontaneous hypoglycemia and mortality was eliminated after adjustment for comorbidities, suggesting that hypoglycemia may be a marker of disease burden rather than a direct cause of death.     

Major Adverse Cardiovascular Events and Mortality in Systemic Lupus Erythematosus Patients After Successful Delivery: A Population-based Study

BackgroundLimited data exist regarding the incidence rate and hazard ratios (HRs) of major adverse cardiovascular events and mortality in the successful-delivery women with or without systemic lupus erythematosus.MethodsA retrospective, population-based cohort study was performed on 1,132,089 parturients from 1999 to 2003. The Kaplan-Meier method and the log-rank test were used to examine the effect of systemic lupus erythematosus on the incidence of major adverse cardiovascular events and mortality. Cox-proportional hazard regression modeling was used to determine the adjusted HRs of systemic lupus erythematosus on the risk of major adverse cardiovascular events and mortality among successful-delivery women.Resultssystemic lupus erythematosus group has the highest risk for major adverse cardiovascular events and mortality. The incidence rate of major adverse cardiovascular events and all-causes mortality among lupus women was 194.67 and 438.82 per 100,000 patients per year, respectively. Lupus women had higher incidence rates of major adverse cardiovascular events, including myocardial infarction, (HR, 54.43; confidence interval [CI], 16.04–184.78; P < 0.0001), heart failure (HR, 11.10; CI, 2.71–45.52; P < 0.0001), percutaneous coronary intervention (HR, 228.32; CI, 43.34–1203.00; P < 0.0001), stroke (HR, 8.02; CI, 3.79–16.99; P < 0.0001) and maternal death (HR, 11.68; CI, 7.97–17.10; P < 0.0001).ConclusionsAlthough major adverse cardiovascular events and mortality are rare events in women of reproductive age, the incidence rates have increased approximately 10-fold among lupus women with successful delivery. Clinicians should note the possibility of persisting major adverse cardiovascular events and death in young women with lupus and successful delivery.     

Fate of individuals with ischemic amputations in the REACH Registry: three-year cardiovascular and limb-related outcomes

ObjectiveTo evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes.MethodsThe REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003–2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up.ResultsPAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P < .001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P = .005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P < .001) and all-cause mortality (21.8% vs. 12.6%, P < .001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P < .001) were noted. Recent (≤1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level.ConclusionsIndividuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of “minor” ischemic amputation may confer an identical systemic risk as “major” leg amputation.     

Interleukin-18 and the risk of future cardiovascular disease among initially healthy women

ObjectiveElevated levels of interleukin (IL)-18 have been implicated in the development of atherosclerosis in animals. Data in humans are less clear, and data in women are particularly scarce.Methods and resultsIn a prospective nested case–control study of initially healthy women, we measured baseline plasma IL-18 levels in 253 participants who subsequently developed cardiovascular disease (CVD) and in 253 healthy age- and smoking-matched controls. IL-18 levels were higher at baseline among those who developed CVD (274.1 pg/mL versus 233.8 pg/mL, P < 0.001), and were associated with future CVD (relative risk (RR) for highest versus lowest quartile 2.53; 95% CI, 1.47–4.35, P < 0.001). While that risk was attenuated after adjustment for traditional cardiovascular risk factors (RR 1.60; 95% CI, 0.77–3.34, P = 0.13), those with IL-18 levels at or above a threshold of the 90th percentile (442 pg/mL) remained at elevated risk after adjustment (RR 2.40; 95% CI, 1.05–5.56, P = 0.04). Levels of IL-18 above this threshold modify the fully adjusted risk of future CVD conferred by elevated levels of total cholesterol (P_interaction = 0.02).ConclusionsIn this population of apparently healthy women, IL-18 levels associate with increased risk of cardiovascular disease, but that risk is attenuated in models adjusting for traditional cardiovascular risk factors. Very high levels of IL-18 interact with hypercholesterolemia to alter CVD risk.     

Impact of contrast-induced acute kidney injury on outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

PurposeThe purpose of this study was to identify predictors of contrast-induced acute kidney injury (CI-AKI) and the effect of CI-AKI on cardiovascular outcomes after hospital discharge in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).Methods and MaterialsWe retrospectively reviewed 194 STEMI consecutive patients who underwent primary PCI to evaluate the predictors for CI-AKI and 187 survivors to examine all-cause mortality and cardiovascular events. Outcomes were compared between patients with CI-AKI and those without CI-AKI, which was defined as an increase > 50% or > 0.5 mg/dl in serum creatinine concentration within 48 hours after primary PCI.ResultsCI-AKI occurred in 23 patients (11.9%). Multivariate analysis identified pre-procedural renal insufficiency as a predictor of CI-AKI, and this predictor was independent from hemodynamic instability and excessive contrast volume. Receiver-operator characteristics analysis demonstrated that patients with an estimated glomerular filtration rate (eGFR) of ≤ 43.6 ml/min per 1.73 m² had the potential for CI-AKI. Patients who developed CI-AKI had higher mortality and cardiovascular events than did those without CI-AKI (27.8% vs. 4.7%; log-rank P = .0003, 27.8% vs. 11.2%; log-rank P = .0181, respectively). Cox proportional hazards model analysis identified CI-AKI as the independent predictor of mortality and cardiovascular events [hazard ratio [HR] = 5.36; P = .0076, HR = 3.10; P = .0250, respectively].ConclusionsThe risk of CI-AKI is increased in patients with pre-procedural renal insufficiency, and eGFR is clinically useful in the emergent setting for CI-AKI risk stratification before primary PCI.     

Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study

ObjectiveSerum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD.MethodsWe measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded.ResultsDuring an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p = 0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p < 0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p = 0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p < 0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09, p = 0.06).ConclusionsHigher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD.     

CRP,IL-6 and endothelin-1 levels in patients undergoing coronary artery bypass grafting. Do preoperative inflammatory parameters predict early graft occlusion and late cardiovascular events?

BackgroundInflammation is a major contributor to atherosclerotic vascular disease. Inflammatory parameters such as C-reactive protein (CRP) and Interleukin-6 (IL-6) have been shown to be strong predictors of cardiovascular events. The association between preoperative inflammatory parameters and early graft occlusion as well as cardiovascular events after coronary artery bypass grafting (CABG) has not, however, been fully elucidated. The aims of the present study were to prospectively investigate the prognostic value of the inflammatory parameters IL-6, CRP, and endothelin (ET-1) to predict early graft occlusion as well as late cardiovascular events after CABG.MethodsIn the present study 99 patients undergoing CABG because of stable angina pectoris due to significant coronary artery disease were prospectively included. Coronary angiography was repeated 3 months after CABG in 81 patients in order to evaluate early graft occlusion. Blood samples were collected before CABG in all patients. Patients were followed up for a median of 5 (3–7) years after CABG.ResultsTwenty-five patients (31%) had one or more occluded grafts at the 3-month control coronary angiography. The patients with occluded grafts had higher preoperative CRP and IL-6 levels in plasma [CRP 2.22 (1.11–4.47) mg/L vs. 1.23 (0.71–2.27) mg/L P = 0.03] and [IL-6 2.88 (1.91–5.94) pg/mL vs. 2.15 (1.54–3.14) pg/mL P = 0.006]. There were 23 late cardiovascular events among the 99 patients during the follow-up. Patients experiencing late cardiovascular events had higher preoperative IL-6 levels than those without late cardiovascular events [4.13 (1.83–5.87) pg/mL vs. 2.08 (1.53–2.29) pg/mL, P = 0.002] whereas CRP levels did not differ significantly between the two groups [1.5 (0.79–4.41) mg/L vs. 1.33 (0.74–2.48) mg/L, P = 0.41]. Looking at IL-6, a cut off value more than 3.8 pg/ml was associated with a significant higher risk for an early graft occlusion (P = 0.04) and late cardiovascular events (P = 0.00003). Preoperative endothelin-1 did not predict early graft occlusions or late cardiovascular events.ConclusionsRaised preoperative IL-6 levels are predictors of both early graft occlusion and late cardiovascular events after CABG. Elevated preoperative CRP levels can predict early graft occlusion after CABG. Endothelin did not differ between the two groups.     

Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT)

BackgroundThe Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) showed that gemfibrozil significantly reduced major coronary events in men with known coronary heart disease (CHD). To better understand why therapy was especially effective with obesity, diabetes, and hyperinsulinemia, changes in body weight and plasma insulin were determined after 1 year of gemfibrozil or placebo therapy and related to changes in lipids and CHD events.ResultsWith gemfibrozil significantly more subjects lost weight (51.7% versus 38.6%, P < 0.0001) and significantly fewer subjects gained weight (42.5% versus 54.0%, P < 0.0001) than with placebo. Both a greater loss and smaller gain in weight with gemfibrozil were age-related and significant in subjects ≥66 years (median age), but not in younger subjects. Weight change was paralleled by changes in insulin. With gemfibrozil, CHD events were significantly reduced with weight loss (hazard ratio [HR], 0.61; 95% CI, 0.44–0.84; P = 0.002) and, particularly, with diabetes or hyperinsulinemia (HR, 0.53; 95% CI, 0.34–0.83; P = 0.006). In contrast, CHD events were not significantly reduced without weight loss (HR, 0.83; 95% CI, 0.62–1.12; P = 0.22).ConclusionsIn VA-HIT, gemfibrozil resulted in weight loss associated with reductions in insulin. With weight loss gemfibrozil produced a significant reduction in CHD events that did not occur in the absence of weight loss.     

Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: a population-based cohort study

ObjectiveThere is debate whether infection with Helicobacter (H.) pylori, the main inducer of chronic atrophic gastritis (CAG), is a risk factor for cardiovascular disease and premature mortality.MethodsSerological measurements of H. pylori infection and pepsinogen (PG) I and II were obtained in a population-based German cohort of 9953 older adults (50–74 years). Cox regression was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for myocardial infarction, stroke, cardiovascular and all-cause mortality during five-year follow-up.ResultsAccording to serology, 4977 participants (51.9%) were infected with H. pylori (2604 with cytotoxin-associated gene A (cagA) strains) and 541 (5.7%) had CAG (PGI < 70 ng/mL and PGI/PGII < 3). During follow-up, 540 participants died (163 from cardiovascular causes), 170 experienced a primary myocardial infarction and 241 had a stroke. Neither cytotoxin-associated gene A (cagA) negative nor cagA positive H. pylori infections were associated with an increased risk for myocardial infarction, stroke or all-cause mortality. Intriguingly, infection with cagA positive H. pylori strains was inversely associated with cardiovascular mortality (HR, 0.62; CI: 0.41–0.94). No statistically significant associations were observed for the small group of participants with CAG, but point estimates of adjusted HRs for myocardial infarction, stroke and cardiovascular mortality were all below 1 (0.71, 0.59 and 0.65, respectively).ConclusionsOur results do not support the hypothesis that H. pylori infection or CAG are risk factors for cardiovascular disease or mortality and instead suggest an inverse relationship of cagA positive H. pylori infection with fatal cardiovascular events.     

Probucol therapy improves long-term (>10-year) survival after complete revascularization: a propensity analysis

ObjectiveProbucol has anti-atherosclerotic properties and has been shown to reduce post-angioplasty coronary restenosis. However, the effect of probucol therapy on long-term (>10 years) outcome following coronary revascularization is less well established. Accordingly, we sought to determine if probucol therapy at the time of complete coronary revascularization reduces mortality in patients with coronary artery disease (CAD).MethodsWe collected data from 1694 consecutive patients who underwent complete revascularization (PCI and/or bypass surgery). Mortality data were compared between patients administered probucol and those not administered probucol at the time of revascularization. A propensity score (PS) was calculated to evaluate the effects of variables related to decisions regarding probucol administration. The association of probucol use and mortality was assessed using 3 Cox regression models, namely, conventional adjustment, covariate adjustment using PS, and matching patients in the probucol and no-probucol groups using PS.ResultsIn the pre-match patients, 231 patients were administered probucol (13.6%). During follow-up [10.2 (SD, 3.2) years], 352 patients died (including 113 patients who died of cardiac-related issues). Probucol use was associated with significant decrease in all-cause death (hazard ratio [HR], 0.65; P = 0.036 [conventional adjustment model] and HR, 0.57; P = 0.008 [PS adjusted model]). In post-match patients (N = 450, 225 matched pair), the risk of all-cause mortality was significantly lower in the probucol group than in the no-probucol group (HR, 0.45; P = 0.002).ConclusionIn CAD patients who had undergone complete revascularization, probucol therapy was associated with a significantly reduced risk of all-cause mortality.     

Supervivencia a largo plazo de una población española con cardiopatía isquémica estable: el registro CICCOR

Introduction and objectivesData are lacking on the long-term prognosis of stable ischemic heart disease (SIHD). Our aim was to analyze long-term survival in patients with SIHD and to identify predictors of mortality.MethodsA total of 1268 outpatients with SIHD were recruited in this single-center prospective cohort study from January 2000 to February 2004. Cardiovascular and all-cause death during follow-up were registered. All-cause and cardiovascular mortality rates were compared with those in the Spanish population adjusted by age, sex, and year. Predictors of these events were investigated.ResultsThe mean age was 68 ± 10 years and 73% of the patients were male. After a follow-up lasting up to 17 years (median 11 years), 629 (50%) patients died. Independent predictors of all-cause mortality were age (HR, 1.08; 95%CI, 1.07-1.11; P < .001), diabetes (HR, 1.36; 95%CI, 1.14-1.63; P < .001), resting heart rate (HR, 1.01; 95%CI, 1.00-1.02; P < .001), atrial fibrillation (HR, 1.61; 95%CI, 1.22-2.14; P = .001), electrocardiographic changes (HR, 1.23; 95%CI, 1.02-1.49; P = .02) and active smoking (HR, 1.85; 95%CI, 1.31-2.80; P = .001). All-cause mortality and cardiovascular mortality rates were significantly higher in the sample than in the general Spanish population (47.81/1000 patients/y vs 36.29/1000 patients/y (standardized mortality rate, 1.31; 95%CI, 1.21-1.41) and 15.25/1000 patients/y vs 6.94/1000 patients/y (standardized mortality rate, 2.19; 95%CI, 1.88-2.50, respectively).ConclusionsThe mortality rate was higher in this sample of patients with SIHD than in the general population. Several clinical variables can identify patients at higher risk of death during follow-up.Full English text available from:www.revespcardiol.org/en     

The impact of prior heart failure hospitalizations on long-term mortality differs by baseline risk of death

BackgroundHospitalizations for decompensated heart failure (HF) are thought to increase long-term mortality. However, previous reports focus on newly hospitalized HF patients or clinical trial populations and do not always adjust for baseline mortality risk. We hypothesized that the number of HF hospitalizations within the prior 12 months would improve overall mortality risk stratification, particularly in otherwise “low-risk” HF inpatients.MethodsWe studied 2221 HF patients admitted to 14 Michigan community hospitals during 2002-2004. We estimated 1-year mortality using the multivariable (Enhanced Feedback For Effective Cardiac Treatment [EFFECT]) model and classified patients as low (EFFECT <90), moderate (90-120), and high risk (>120). We used logistic regression and stratified Cox proportional hazard modeling to explore the overall EFFECT model performance and the influence of HF hospitalizations within the prior 12 months on mortality risk.ResultsThe EFFECT model adequately predicted and stratified for 1-year mortality (odds ratio 1.35 [95% confidence interval (CI), 1.30-1.40] per 10 points, P <.001, C-statistic 0.698), with low-, moderate-, and high-risk group mortality 18%, 35%, and 58%, respectively. The number of prior HF hospitalizations only modestly improved overall discrimination (C-statistic 0.704, P = .04). However, in low-risk patients the number of prior HF hospitalizations progressively increased the hazard for 1-year mortality (none: mortality 13%; 1: mortality 20%, hazard ratio [HR] 1.50 (95% CI, 0.86-2.60), P = .15; 2 or 3: mortality 27%, HR 2.24 (95% CI, 1.39-3.60); P = .001; 4 or more: mortality 31%, HR 2.80 (95% CI, 1.70-4.63); P <.001; P <.001 for trend). There was no consistent relationship between prior HF hospitalizations and 1-year mortality in moderate- or high-risk HF patients.ConclusionIn otherwise “low-risk” HF inpatients, a history of 2 or more HF hospitalizations within the prior 12 months markedly increases 1-year mortality risk. This easily obtained information could help allocate specialized HF resources to the subset of “low-risk” patients most likely to benefit.     

Impact of dyslipidaemia on arterial structure and function in urban indigenous Australians

BackgroundPremature cardiovascular disease (CDV) is highly prevalent in urban Indigenous Australians. We studied arterial structure and function in 144 volunteers aged 15–66 years to assess the role of dyslipidaemia and other traditional vascular risk factors on cardiovascular risk in young and older urban Indigenous Australians.MethodsWe assessed carotid intima-media thickness (CIMT) by high-resolution B-mode ultrasound imaging of the common carotid artery and peripheral wave reflection using applanation tonometry to obtain the aortic augmentation index (AI) in Indigenous Australian participants of the Darwin Region Urban Indigenous Diabetes (DRUID) study.ResultsParticipants aged 15–24 years demonstrated fewer cardiovascular risk factors than the older group (25–66 years) and predictors of CIMT and AI differed between younger and older groups. CIMT was higher in the older group (0.67 mm vs. 0.61 mm, p = 0.004) and in those with diabetes (0.81 mm vs. 0.67 mm, p < 0.001). AI was higher in the older group (24% vs. 0%, p < 0.001), but was not affected by diabetes status. On multivariate regression analysis, low HDL-cholesterol was the only independent predictor of CIMT in the younger group; triglycerides, heart rate (inverse) and height (inverse) were independent predictors of AI in the same group.ConclusionDyslipidaemia (low HDL-cholesterol or elevated triglycerides) is independently associated with non-invasive measures of cardiovascular disease in a relatively healthy and young subgroup of this high-risk population. We propose that triglycerides and low HDL-cholesterol may represent the most useful commonly measured clinical indicators of cardiovascular risk in young, urban Indigenous Australians.     

Different prognostic value of silent peripheral artery disease in type 2 diabetic and non-diabetic subjects with stable cardiovascular disease

ObjectiveABI is a good predictor of morbidity and motality in diabetic subjects with no known cardiovascular disease. However, its prognostic value in diabetic patients with prior coronary or cerebrovascular disease has not previously been evaluated.MethodsMulticenter, prospective study of 1 year of follow-up, in 1096 patients (73.6 years, 65% males, 45.4% with diabetes) with cardiovascular disease and without known peripheral arterial disease. The main outcome measure was the first occurrence of a major cardiovascular event (non-fatal acute coronary syndrome, non-fatal stroke, revascularization procedure, or cardiovascular death). Secondary endpoints included major cardiovascular events, cardiovascular death and death from any cause.ResultsPrevalence of an abnormal ABI (<0.9 or >1.4) was 38.2% in diabetic and 26.8% in non-diabetic subjects. There were 150 major cardiovascular events (38.3/1000 person-years in diabetics vs. 30.6/1000 person-years in non-diabetics subjects, p = 0.012) and 60 cardiovascular deaths (11.8/1000 person-years in diabetics vs. 10.7/1000 person-years in non-diabetics subjects, p = 0.156). Patients with abnormal ABI had a higher rate of vascular complications. There was a significant interaction between ABI and diabetes. In non-diabetic patients, an abnormal ABI was associated with an increase risk of the primary endpoint (HR 2.71; 95% CI 1.54–4.76), cardiovascular mortality (HR 4.62; 95% CI 1.47–14.52) and total mortality (HR 2.80; 95% CI 1.08–7.27). These associations were not observed in patients with diabetes.ConclusionIn patients with cardiovascular disease, ABI is a good predictor of risk of recurrent cardiovascular events and death, only in non-diabetic subjects.     

Metabolic syndrome, abdominal obesity, and cardiovascular risk in elderly women

BackgroundMetabolic syndrome and abdominal obesity are risk factors for cardiovascular diseases in middle age women but, not completely understood in older people. In this study we analyzed the association between metabolic syndrome and abdominal obesity and the occurrence of cardiovascular events in these elderly women.MethodsA prospective follow-up study included 516 consecutive women aged 60–84 years who sought medical care at a geriatric outpatient facility. The presence of metabolic syndrome and higher quartiles of waist circumference and waist-to-hip ratio were analyzed as predictive variables, and were adjusted for age, smoking, and previous cardiovascular diseases. The outcomes were the occurrence of stroke, myocardial infarction, evidence of coronary artery disease, or cardiovascular death.ResultsDuring a mean follow-up of 6.6 years, 94 (18.2%) cardiovascular events were observed (48 fatal and 46 non-fatal). Metabolic syndrome was diagnosed in 206 women (39.9%). After adjustments for confounding variables, metabolic syndrome and waist-to-hip ratio above the 75th percentile (> 0.98) were predictors of the outcomes, but greater waist circumference (> 96 cm) was not. Adjusted hazard ratios for these variables were: metabolic syndrome, 1.66, 95% CI − 1.11 to 2.47, p = 0.01; waist-to-hip ratio, 1.72, 95% CI − 1.05 to 2.82; p = 0.03 and waist circumference, 1.37, 95% CI − 0.91 to 2.07, p = 0.12.ConclusionMetabolic syndrome and high waist-to-hip ratio were associated with increased risk of cardiovascular events in the studied sample.     

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.     

Glycemic Status and Incident Heart Failure in Elderly Without History of Diabetes Mellitus: The Health, Aging, and Body Composition Study

BackgroundIt is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).Methods and ResultsThe association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A_1c [HbA_1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new-onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health, Aging, and Body Composition Study (median age, 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate was 10.7 cases per 1000 person-years with FG <100 mg/dL, 13.1 with FG 100–125 mg/dL, and 26.6 with FG ≥126 mg/dL (P = .002; P = .003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate [HR], and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10 mg/dL, 1.10; 95% CI, 1.02–1.18; P = .009); the addition of OGTT, fasting insulin, HbA_1c, HOMA-IR, or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n = 69), FG showed a strong association in adjusted models (HR per 10 mg/dL, 1.15; 95% CI, 1.03–1.29; P = .01). In comparison, when only HF with LVEF >40%, was considered (n = 71), the association was weaker (HR per 10 mg/dL, 1.05; 95% CI; 0.94–1.18; P = .41).ConclusionsFasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.