Cardiovascular Disease Events In Patients Research Articles

Abstract 16978: Midregional Pro-Atrial Natriuretic Peptide and Risk of Recurrent Cardiovascular Disease Events in Patients with Stable Coronary Heart Disease Followed Over 8 Years

Aim: Natriuretic peptides provide valuble information about cardiac dysfunction. The clinical relevance of elevated circulating midregional pro-atrial natriuretic peptide (MR-proANP) in patients with stable coronary heart disease (CHD) several weeks after an acute event has not been fully evaluated. We aimed to assess the predictive value of MR-proANP for recurrent cardiovascular disease (CVD) events in stable CHD patients, simultaneously controlling for a large number of potential confounders. Methods: Plasma concentrations of MR-proANP (BRAHMS) were measured at baseline in a cohort of 1,048 patients aged 30-70 years with CHD. The Cox proportional hazards model was used to determine the prognostic value of MR-proANP on a combined CVD endpoint after adjustment for covariates. Results: The median MR-proANP level was 135.2 pmol/L (interquartile range 95.2-185.8). Elevated MR-proANP levels were associated with higher age, obesity, history of hypertension, diabetes, and heart failure, higher number of affected vessels, initial management of CHD, and left-ventricular dysfunction in a statistically significant way. Furthermore, after adjustment for age and gender MR-proANP was correlated with CRP (correlation coefficient (R=0.21), NT-proBNP (R=0.72), creatinine clearance (R= -0.32), cystatin C (R=0.43), hsTnT (R= 0.51) respectively (all p-values <0.0001). During a median follow-up of 8.1 years, 150 patients (21.1%) experienced a fatal- or non-fatal secondary CVD event. In a multivariate model MR-proANP was associated with a hazard ratio (HR) of secondary CVD events of 3.00 (95% confidence interval (CI), 1.70-5.28) when extreme quartiles were compared. Further adjustment for NT-proBNP attenuated the association only slightly (HR 2.67; 95% CI, 1.48-4.79). Conclusions: Elevated MR-proANP levels in stable CHD patients are associated with several CVD disorders and predict long-term CVD events in these patients.

Metabolic syndrome is an independent risk factor for cardiovascular disease events in patients with ischemic stroke

To explore the association between metabolic syndrome (MS) and risk of cardiovascular disease events (CVD) in patients with ischemic stroke. A total of 1087 patients with ischemic stroke were enrolled from 5 community-based medical centres and underwent baseline evaluation on risk factors of stroke during the period of Jan. 2003 to Dec. 2006. After baseline survey, all patients were followed up until Dec 31, 2008 and new CVD events were recorded. MS was defined using CDS criteria. Proportional hazard models were used to assess the HRs and 95% CI of CVD events associated with MS and other components. The prevalence of MS was 40.4% at baseline. During an average follow-up of 3.5 years, 178 patients developed new CVD events. After adjusted for age, gender, smoking, drinking, marriage status, education level, hospitalization, recurrence of stroke, stroke duration, depression, cognition impairment and ADL, MS remains the independent predictor for the risk of CVD events. Compared with patients with non-MS, the risk of CVD events increased by 44% (HR: 1.44, 95%CI: 1.06 - 1.95). The risk of CVD also increased with the number of MS components. Compared with patients with 1 or less than 1 components of MS, the risk of CVD events increased by 30% (HR: 1.30, 95% CI: 0.83 - 2.04) in those with 2 components and by 69% (HR: 1.69, 95%CI: 1.11 - 2.56) in those with 3 or more components of MS. Hypertension and hyperglycemia and impaired fasting glucose also served as independent risk factors for CVD event (all P < 0.001). MS was independently associated with increased risk of CVD events in patients with ischemic stroke. There was a dose-response relationship between the numbers of MS components and the risk of CVD event.

Risk of Cardiovascular Disease Events in Patients With Type 2 Diabetes Prescribed the Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist Exenatide Twice Daily or Other Glucose-Lowering Therapies

OBJECTIVETo test the hypothesis that exenatide twice daily reduces the relative incidence of cardiovascular disease (CVD) events among patients with type 2 diabetes compared with other glucose-lowering agent(s).RESEARCH DESIGN AND METHODSA retrospective database analysis was performed of the LifeLink database of medical and pharmaceutical insurance claims for June 2005 through March 2009. Patients with no history in the preceding 9 months of myocardial infarction, ischemic stroke, or coronary revascularization procedure were assigned to the exenatide-initiated or non–exenatide-initiated cohorts based on the first new prescription filled and reassigned if exenatide was prescribed or discontinued. Incident CVD events (myocardial infarction, ischemic stroke, or coronary revascularization procedure) were identified by ICD-9-CM diagnosis codes. Patient outcomes were adjusted for differences in clinical and demographic characteristics and compared using propensity score–weighted discrete time survival analysis with time-varying exposure to exenatide.RESULTSA total of 39,275 patients with type 2 diabetes were treated with exenatide twice daily, and 381,218 patients were treated with other glucose-lowering therapies. Patients who initiated exenatide were more likely to have prior ischemic heart disease, obesity, hyperlipidemia, hypertension, and/or other comorbidities at baseline. Exenatide-treated patients were less likely to have a CVD event than non–exenatide-treated patients (hazard ratio 0.81; 95% CI 0.68–0.95; P = 0.01) and lower rates of CVD-related hospitalization (0.88; 0.79–0.98; P = 0.02) and all-cause hospitalization (0.94; 0.91–0.97; P < 0.001).CONCLUSIONSExenatide twice-daily treatment was associated with a lower risk of CVD events and hospitalizations than treatment with other glucose-lowering therapies.

ACCORD Blood Pressure and ACCORD Lipid: how low can we go?

Lowering blood pressure to normal levels, below those currently recommended, does not reduce the risk of cardiovascular disease events in patients with type 2 diabetes mellitus. Nor does treating dyslipidemia with fibrate and statin combination therapy reduce the risk of cardiovascular disease events more than treatment with statin alone.

Insights from recent meta-analysis: Role of high-density lipoprotein cholesterol in reducing cardiovascular events and rates of atherosclerotic disease progression

Although low-density lipoprotein cholesterol (LDL-C) traditionally has been the focus of treatment guidelines and clinical trials of lipid therapy, patients continue to have cardiovascular disease (CVD) events despite effective lowering of their LDL-C levels, suggesting the influence of other risk factors. High-density lipoprotein cholesterol (HDL-C) levels have been shown to be inversely associated with CVD risk in epidemiological studies. Meta-analyses and clinical trials that reported on the potential relation between HDL-C and CVD were reviewed. Low HDL-C level is associated with increased CVD risk. Statins reduce CVD events in patients with low HDL-C, and fibrates benefit patients with low HDL-C and high triglyceride levels. The benefit of statins on event reduction may be related to their effects on HDL-C. However, not all therapies that increase HDL-C reduce CVD events. Imaging trials have provided evidence of the combined influence of HDL-C and LDL-C on surrogate end points. Drugs in the same class may have different effects on HDL-C, and these different lipid effects may translate into different effects on atherosclerosis and CVD events. A new class of agents, cholesteryl ester transfer protein inhibitors, is being examined in ongoing trials to determine whether dalcetrapib may have different effects than torcetrapib, which increased levels of HDL-C but was associated with increased adverse events. In addition, ongoing trials are examining whether targeting both HDL-C and LDL-C, by combining a second agent such as niacin with a statin, leads to greater benefit on CVD and clinical events.

Serum vitamin D and risk of secondary cardiovascular disease events in patients with stable coronary heart disease

Recent longitudinal analyses suggested that low levels of serum 25-hydroxyvitamin D (25-OH-D) predict incident cardiovascular disease in initially healthy populations. Because the prognostic value of vitamin D for the occurrence of secondary cardiovascular events remains unclear, we examined the association of baseline 25-OH-D levels with prognosis in patients with stable coronary heart disease (CHD). Serum 25-OH-D levels from 1,125 CHD patients of 2 German clinics undergoing a 3-week rehabilitation program after an acute cardiovascular event were measured, and participants were followed for up to 8 years. We used multivariate Cox regression analysis to model cardiovascular event incidence (fatal and nonfatal, including myocardial infarction, stroke, and death due to cardiovascular diseases) and all-cause mortality according to 25-OH-D quartiles, categories based on cut points of 15 and 30 ng/mL, or continuous vitamin D concentrations. During follow-up, 148 cardiovascular events and 121 deaths were recorded. Elevation of risk for the lowest quartile or category in comparison to the highest category was weak and nonsignificant for both incidence (hazard ratio [HR](quartile1) = 1.15 [0.72-1.84], HR(<15 ng/mL) = 1.17 [0.61-2.23]) and mortality (HR(quartile1) = 1.29 [0.77-2.14], HR(<15 ng/mL) = 1.87 [0.91-3.82]) in unadjusted Cox regression analysis and disappeared entirely after adjustment for potential confounders (cardiovascular events: HR(quartile1) = 0.84 [0.47-1.50], HR(<15 ng/mL) = 0.90 [0.41-1.96]; mortality: HR(quartile1) = 0.63 [0.33-1.21], HR(<15 ng/mL) = 0.93 [0.39-2.21]). Models treating vitamin D as a continuous variable likewise suggested no significant associations. Unlike previous population-based studies, our analysis in high-risk patients with stable CHD does not support a prognostic value of baseline-25-OH-D levels for secondary cardiovascular event incidence or all-cause mortality.

The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review

Patients with RA have an increased prevalence of cardiovascular disease (CVD). This is due to traditional risk factors and the effects of chronic inflammation. MTX is the first-choice DMARD in RA. We performed a systematic literature review to determine whether MTX affects the risk of CVD in patients with RA. We searched Medline, Embase, Cochrane database, database of abstracts of reviews of effects, health technology assessment and Science Citation Index from 1980 to 2008. Conference proceedings (British Society of Rheumatology, ACR and EULAR) were searched from 2005 to 2008. Papers were included if they assessed the relationship between MTX use and CVD in patients with RA. Two reviewers independently assessed each title and abstract for relevance and quality. A total of 2420 abstracts were identified, of which 18 fulfilled the inclusion criteria. Two studies assessed the relationship between MTX use and CVD mortality, one demonstrated a significant reduction in CVD mortality and the second a trend towards reduction. Five studies considered all-cause CVD morbidity. Four demonstrated a significant reduction in CVD morbidity and the fifth a trend towards reduction. MTX use in the year prior to the development of RA decreased the risk of CVD for 3-4 years. Four studies considered myocardial infarction, one demonstrated a decreased risk and three a trend towards decreased risk with MTX use. The current evidence suggests that MTX use is associated with a reduced risk of CVD events in patients with RA. This suggests that reducing the inflammation in RA using MTX not only improves disease-specific outcomes but may also reduce collateral damage such as atherosclerosis.

Administration of alfacalcidol for patients with predialysis chronic kidney disease may reduce cardiovascular disease events

Besides its effect on calcium metabolism, vitamin D may play a part in preventing the onset and progression of cardiovascular disease (CVD) events. Only a few reports on the studies relating to whether vitamin D may reduce CVD events in patients with predialysis chronic kidney disease (CKD) are available, and many ambiguities remain. We conducted a retrospective cohort study of 665 patients with predialysis CKD. With log-rank test using the Kaplan-Meyer survival curve, comparison of incidences of CVD events, CVD-related mortality, and all-cause mortality were made between patients in the alfacalcidol treatment group (107 patients) in the predialysis stage to whom alfacalcidol 0.25-0.5 microg/day was orally administered for at least 24 weeks, and patients in the nontreatment group (558 patients) who received no administration of alfacalcidol or other type of activated vitamin D and its analogues. Patients to whom alfacalcidol administration was discontinued within 24 weeks as well as initiation of dialysis of <24 weeks were excluded for this study. Factors relating to CVD events were examined using Cox's proportional hazards analysis. The mean follow-up period was 55.1 +/- 38.9 months in the alfacalcidol treatment group and 41.9 +/- 38.4 months in the nontreatment group. CVD events occurred in 172 patients during the follow-up period, and 74 of those occurred during the predialysis period. In the alfacalcidol treatment group, the incidence of cumulative CVD events was significantly lower. In relation to all-cause deaths and CVD-related deaths, the cumulative mortality rate was significantly lower in the alfacalcidol treatment group during the follow-up period. Throughout the follow-up period, the association between CVD events and alfacalcidol use was detected when adjusted for age, sex, diabetes, hypertension, use of renin-angiotensin system inhibitors, estimated glomerular filtration rate, and albumin and parathyroid hormone. These data showed that oral administration of alfacalcidol for predialysis CKD patients was associated with reduced risk for CVD.

Aspirin for the Primary Prevention of Cardiovascular Events: An Update of the Evidence for the U.S. Preventive Services Task Force

Coronary heart disease and cerebrovascular disease are leading causes of death in the United States. In 2002, the U.S. Preventive Services Task Force (USPSTF) strongly recommended that clinicians discuss aspirin with adults who are at increased risk for coronary heart disease.To determine the benefits and harms of taking aspirin for the primary prevention of myocardial infarctions, strokes, and death.MEDLINE and Cochrane Library (search dates, 1 January 2001 to 28 August 2008), recent systematic reviews, reference lists of retrieved articles, and suggestions from experts.English-language randomized, controlled trials (RCTs); case-control studies; meta-analyses; and systematic reviews of aspirin versus control for the primary prevention of cardiovascular disease (CVD) were selected to answer the following questions: Does aspirin decrease coronary heart events, strokes, death from coronary heart events or stroke, or all-cause mortality in adults without known CVD? Does aspirin increase gastrointestinal bleeding or hemorrhagic strokes?All studies were reviewed, abstracted, and rated for quality by using predefined USPSTF criteria.New evidence from 1 good-quality RCT, 1 good-quality meta-analysis, and 2 fair-quality subanalyses of RCTs demonstrates that aspirin use reduces the number of CVD events in patients without known CVD. Men in these studies experienced fewer myocardial infarctions and women experienced fewer ischemic strokes. Aspirin does not seem to affect CVD mortality or all-cause mortality in either men or women. The use of aspirin for primary prevention increases the risk for major bleeding events, primarily gastrointestinal bleeding events, in both men and women. Men have an increased risk for hemorrhagic strokes with aspirin use. A new RCT and meta-analysis suggest that the risk for hemorrhagic strokes in women is not statistically significantly increased.New evidence on aspirin for the primary prevention of CVD is limited. The dose of aspirin used in the RCTs varied, which prevented the estimation of the most appropriate dose for primary prevention. Several of the RCTs were conducted within populations of health professionals, which potentially limits generalizability.Aspirin reduces the risk for myocardial infarction in men and strokes in women. Aspirin use increases the risk for serious bleeding events.

Plasma Parathyroid Hormone Level and Prevalent Cardiovascular Disease in CKD Stages 3 and 4: An Analysis From the Kidney Early Evaluation Program (KEEP)

Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). Secondary hyperparathyroidism is common in patients with CKD, and its relationship to CVD is not well defined. This analysis aims to assess whether serum intact parathyroid hormone (PTH) level is an independent risk factor for CVD in patients with CKD stages 3 and 4. In this cross-sectional study, medical history surveys, including CVD events, were collected from 4,472 patients with stages 3 and 4 CKD identified by the National Kidney Foundation Kidney Early Evaluation Program (KEEP), which included blood pressure measurement and laboratory testing. Age, hemoglobin level, estimated glomerular filtration rate, serum phosphorus level, and serum calcium level were evaluated as continuous variables, and plasma PTH levels, by tertile: less than 35, 35 to 70, and greater than 70 pg/mL. Multivariate logistic regression was used to estimate odds ratios (ORs) of CVD predictor variables. Mean age was 68.3 +/- 11.8 years. Of the study population, 68% were women, 69% were white, 6% were current smokers, 45% were obese, 46% had diabetes, and 83% had hypertension. A history of CVD was present for 1,972 (44.1%), and plasma PTH level greater than 70 pg/mL, for 2,239 (50.1%). Multivariate logistic regression showed ORs for CVD events increasing with age (OR, 1.03; P < 0.001), male sex (OR, 1.51; P < 0.001), diabetes (OR, 1.73; P < 0.001), hypertension (OR, 1.43; P < 0.001), and intact PTH level greater than 70 pg/mL (OR, 1.51; P < 0.001; reference, <35 pg/mL). PTH level greater than 70 pg/mL is independently associated with CVD events in patients with CKD stages 3 and 4. No association was observed between serum phosphorus or calcium level and CVD events. These findings provide support for intact PTH testing, along with testing for other indicators of CKD mineral and bone disorders, at earlier CKD stages.

Cardiovascular Disease in Patients with Hemophilia: Single Centre Experience.

Background: Cardiovascular disease (CVD) is at epidemic levels (37%, Heart Disease and Stroke Statistics, 2008 Update) in the US and is also affecting hemophilia patients. Conflicting reports exist concerning the potential protective effect of hemophilia on the occurrence of CVD.Objective: To evaluate the prevalence and risk factors of CVD events in patients with hemophilia ≥40 years old.Methods: This cross sectional study included all patients with hemophilia followed at Indiana Hemophilia and Thrombosis Center (IHTC) from January 2004 to June 2008. The following data were obtained from patient medical records: demographics; hemophilia severity; inhibitor history; HIV/HCV infection; established CVD risk factors including body mass index (BMI), hypertension, diabetes, smoking, hypercholesterolemia, and lipid profiles; information on CVD events; and cause of death. CVD events were defined as documented ischemic heart disease, coronary artery disease, and stroke/transient ischemic attacks due to hypertension/atherosclerosis. Univariate and multivariate analyses were performed to identify risk factors for CVD in this population.Results: A total of 174 patients were identified; 17 (9.7%) were excluded due to incomplete medical records. Population characteristics are described in Table I. Compared to hemophilia A, hemophilia B patients were more frequently obese, hypertensive and prone to cardiac events (Table I). The life-time prevalence of CVD events for the entire cohort was 22.9% (36/157; 95% CI 16.7 to 29.7%). Mortality rate for the entire cohort was 10.8% (17/157); CVD contributed to 64.7% (11/17) of deaths. For hemophilia A, hypertension, high cholesterol, smoking, obesity/elevated BMI were associated with risk of CVD events while HCV infection and low HDL showed a trend towards significance. For hemophilia B, age, hypertension and presence of diabetes were associated with CVD events while smoking showed a trend towards significance. In multivariate analysis, older age, presence of hypertension, and smoking were predictors of CVD. Type and severity of hemophilia, presence of HIV/HCV infection, lipid profile abnormalities, HCV infection and inhibitor history did not influence the CVD risk. The loss of a considerable number of severe hemophilics due to HIV related deaths over the last two decades may have influenced the demographics of the study cohort.Conclusion: This single center study underscores the increasing burden of CVD in patients with hemophilia in the US, implying that the diagnosis of hemophilia regardless of severity does not confer a protective effect against CVD. Routine screening for CVD thus should be mandatory for hemophilia patients after the age of 40 years.Table I: Patient characteristics of hemophilia A and BVariableHemophilia A (N=81)Hemophilia B (N=76)P valueSeveritySevere21 (25.9%)21 (27.63%)0.001Moderate15 (18.5%)32 (42.10%)Mild45 (55.6%)23 (30.26%)Age (decade)40–5035 (43.2%)28 (36.8%)0.75751–6024 (29.6%)20 (26.3%)61–7016 (19.8%)19 (25%)>706 (7.4%)9 (11.9%)Mean Age (yrs)54±11.3257.35±130.092HypertensionNo56 (69.1%)42 (55.3%)0.041Yes24 (29.6%)34 (44.7%)Cholesterol (↑)No50 (61.7%)34 (44.7%)0.103Yes21 (25.9%)27 (35.5%)Missing data10 (12.3%)15 (19.75)DiabetesNo72 (88.9%)63 (82.9%)0.0359Yes9 (11.1%)13 (17.1%)ObesityNo64 (79.0%)35 (46.1%)0.001Yes16 (19.8%)40 (52.6%)HIVNo21 (25.9%)73 (96.1%)0.000Yes59 (72.8%)3 (3.9%)HCVNo21 (25.9%)29 (38.2%)0.125Yes59 (72.8%)47 (61.8%)InhibitorNo75 (92.6%)75 (98.7%)0.059Yes5 (6.2%)1 (2.3%)CVD eventsNo66 (81.5%)55 (72.4%)0.189Yes15 (18.5%)21 (27.6%)CVD event typeCardiac9/15 (60%)18/21 (85.7%)0.03Stroke/TIA8/15 (53.3%)5/21 (23.8%)0.563Table II: Multivariate analysis showing association between variables and cardiovascular events for the entire cohort95% Wald Confidence LimitsVariableOdds ratioLower limitUpper limitHypertension5.771.7718.84Smoking5.991.9218.72Hemophilia B versus A1.870.5486.38Age (51–60 years versus 40–50 years)13.402.5969.44Age group (61–70 years versus 40–50 years)4.140.7821.871Age group (>70 years versus 40–50 years)44.465.72345.75Disease severity (Moderate versus Mild)2.220.578.70Disease severity (Severe versus Mild)4.040.7721.23Diabetes2.900.8410.10Obesity0.4910.1491.615

Abstract 5070: Progression of Urine Albumin Excretion Despite of Optimized Therapies to Reduce Atherosclerotic Risk Factors has an Adverse Outcome in Patients with Coronary Artery Disease

Although microalbuminuria is considered a strong risk factor of future cardiovascular disease (CVD), it remains unclear whether changes in urine albumin excretion (UAE) in response to a reduction of coronary risk factors may provide prognostic information in patients with coronary artery disease (CAD). Thus, this study assessed the hypothesis that changes in UAE in response to optimized therapy for reduction of CAD risk may predict future CVD events in patients with CAD. This study enrolled of 213 patients with newly diagnosed CAD who had microalbuminuria (30 mg/day ≤ UAE &lt; 300 mg/day) at entry. Patients with late-stage chronic kidney disease (GFR &lt; 60 ml/min/1.73 m 2 ) at entry were excluded. All patients had individualized, optimized therapies including medications and recommended life style changes to reduce risk factors for CAD according to AHA guidelines. All patients had a repeated test of UAE at 6 months (2 nd test) after the 1 st UAE test. Thereafter, all patients were prospectively followed up for 3 years or until the occurrence of 1 of the following events: CVD death, nonfatal myocardial infarction, unstable angina pectoris requiring revascularization, or ischemic stroke. Progression of UAE at the 2 nd test was defined as &gt; 50% increase from the UAE at the 1 st test. UAE at 2 nd test was progressed in 62 (29%) patients, while it was not progressed in the remaining 151 (71%) patients. UAE at entry was comparable between patients with and without progression of UAE (52 ± 6.2 vs.61 ± 4.7 mg/day, respectively, p = ns). During follow-up period, events occurred in 15 (24%) of the 62 patients with progression of UAE and in 16 (10%) of the 151 patients without progression of UAE (p &lt; 0.01 by chi-square test). Using a multivariate Cox hazards analysis, progression of UAE was a predictor of future CVD events that was independent of UAE at 1 st test, use of medications, age, and traditional CAD risk factors (HR 2.5, 95%CI 1.2 – 4.8, p = 0.01). Progression of urine albumin excretion despite individualized and optimized therapies to reduce CAD risk factors represents an adverse outcome in CAD patients. Periodic measurement of urine albumin excretion may be useful for risk stratification in CAD.

Abstract 3484: High Plasma Levels of Endogenous Free Dopamine Predict an Adverse Outcome in Patients with Heart Disease and Chronic Kidney Disease

Sympathetic activity is heightened in chronic kidney disease (CKD). The increased sympathetic activity is a risk of future cardiovascular disease (CVD) events. Dopamine, a precursor of norepinephrine biosynthesis, is metabolized in the kidney and excreted into urine, and its plasma levels are increased in renal dysfunction. Thus, we examined whether plasma levels of endogenous dopamine may be related to future CVD events in patients with CKD. A total of 840 patients in stable condition with chronic heart disease (622 patients with ischemic heart disease and 218 with non-ischemic heart disease) (586 patients with GFR ≥ 60 ml/min/1.73 m 2 [normal/mild CKD]; 153 patients with 60 &gt; GFR ≥ 30 [moderate CKD]; 101 patients with 30 &gt; GRF [advanced CKD]) were prospectively followed-up for 5 years or until one of the following CVD events: cardiac death, non-fatal myocardial infarction, unstable angina pectoris requiring unplanned revascularization, worsening heart failure requiring hospitalization, or stroke. Plasma levels of endogenous free dopamine at entry were measured by high-performance liquid chromatography. Patients with a higher stage of CKD had higher dopamine levels than patients with a lower stage (63.0 ± 5.5, 45.0 ± 5.1, and 26 ± 1.2 pg/mL, respectively, ρ = 0.54, p &lt; 0.0001 Spearman rank correlation test). During the follow-up period, 233 patients had CVD events (cardiac death in 54, myocardial infarction in 18, others events in 161) (113 events [19%] in normal/mild CKD, 64 [42%] in moderate CKD, and 56 [55%] in advanced CKD). In patients with moderate CKD and advanced CKD, higher dopamine levels (≥ 40 pg/mL, defined by ROC analysis) were the strongest predictor of CVD events (HR 2.1 and 3.3, 95% CI 1.2 – 3.7 and 1.5 – 7.2, p = 0.006 and 0.003, respectively) in a multivariate Cox hazards analysis using plasma norepinephrine and BNP levels, hypertension, and hyperlipidemia as covariates. In contrast, dopamine levels did not have predictive value in normal/mild CKD (HR 1.2, 95% CI 0.7 – 2.0, p = 0.5). High plasma levels of endogenous free dopamine are a risk factor for future CVD in patients with CKD independently of norepinephrine levels. Increases in plasma endogenous free dopamine levels may serve as a mechanistic link between CKD and CVD.

Effect of Angiotensin Receptor Blockers on Cardiovascular Events in Patients Undergoing Hemodialysis: An Open-Label Randomized Controlled Trial

Cardiovascular disease is the leading cause of mortality in patients with kidney failure treated with hemodialysis (HD). Although angiotensin receptor blockers (ARBs) reduce cardiovascular disease (CVD) events in patients with diabetes and chronic kidney disease, their effect in patients with kidney failure on HD therapy is not known. Open-labeled randomized trial. Patients aged 30 to 80 years receiving HD 2 to 3 times weekly for 1 to 5 years at 5 university-affiliated dialysis centers. Treatment with ARBs (valsartan, candesartan, and losartan) versus without ARBs after stratification by sex, age, systolic blood pressure, and diabetes. The primary end point is the development of fatal and nonfatal CVD events, defined as the composite of CVD death, myocardial infarction, stroke, congestive heart failure, coronary artery bypass grafting, or percutaneous coronary intervention. The secondary end point is all-cause death. 366 subjects initially were randomly assigned to an ARB or no ARB (control), but after a run-in phase, 180 were retained in each group. Mean age was 60 years, 59% were men, 51% had diabetes, and mean predialysis systolic blood pressure was 154 mm Hg. There were 93 fatal or nonfatal CVD events (52%); 34 (19%) in the ARB group and 59 (33%) in the non-ARB group. After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002). There were 63 deaths (35%); 25 (14%) in the ARB group and 38 (21%) in the non-ARB group. After adjustment, all-cause mortality differed between the 2 groups (hazard ratio, 0.64; 95% confidence interval, 0.39 to 1.06; P = 0.1). Because of the small sample size of this trial, the large effect may be a spurious finding. Use of an open-label design and 3 different agents in the ARB group might have influenced results. Use of an ARB may be effective in reducing nonfatal CVD events in patients undergoing long-term HD. A larger study is required to confirm these results.

The impact of fish‐oil supplements on insulin sensitivity

Background: Insulin resistance is a condition in which the amount of insulin released is inadequate to produce a normal glucose response from fat, muscle and liver cells. Its prevalence is increasing, affecting approximately 25% of the UK population (Diabetes UK, 2006) and with it the risk of developing type 2 diabetes and cardiovascular disease (CVD). One of the major contributing factors to insulin resistance is obesity, the incidence of which is also on the rise in the UK (Zaninotto et al.,2006). Medication and lifestyle changes can be implemented to improve insulin sensitivity but whilst the use of fish oils to improve cardiovascular risk is well documented (Erkkila et al., 2003) its effect on insulin sensitivity are less well known. The aim of the study was to determine the effects of 60 days of fish oil supplementation on insulin sensitivity, plasma glucose and insulin levels as assessed by an oral glucose tolerance test (OGTT), total serum cholesterol levels and serum triglyceride (TG) levels.Method: Subjects (n = 5) from Surrey, UK, were selected based on BMI (≥25 kg m−2) and waist circumference (&gt;37 inches for men and &gt;31 inches for women) and current oily fish consumption (no fish oil supplements and &lt;2 portions of oily fish per week). Selected subjects self‐reported to be otherwise mentally and physically healthy. This was a single‐blind intervention study with all subjects being placed on fish oil supplements [n‐3 Polyunsaturated fatty acid (PUFA) (100%); 440 mg Docosahexaenoic acid (DHA), 660 mg Eicosapentaenoic acid (EPA)] for 60 days. An oral glucose tolerance test (OGTT) over 120 min was completed to assess fasting plasma insulin and glucose levels and glucose response over time. Fasting serum triglycerides (TG's) and total cholesterol were also measured from baseline blood samples and blood pressure and anthropometric measurements taken before and after supplementation with the fish oils. Dietary intake was assessed and subjects’ insulin sensitivity and b‐cell function assessed using the homeostatic model assessment (HOMA). Data was analysed using SPSS (v14) with non‐parametric statistics, performed due to the small sample size.Results: Following supplementation there was a significant decrease in diastolic blood pressure (Z = −2.03; P = 0.042), but no other significant changes in anthropometric measurements (Table 1). There was an increase in insulin sensitivity following supplementation as demonstrated by a reduction in the plasma glucose response during the OGTT, and a mean reduction in serum TG's and total cholesterol, although these were not statistically significant (Table 1). Data for the anthropometric measurements, TAG, total cholesterol, fasting plasma glucose and insulin levels and insulin resistance (HOMA‐IR) and b‐cell function (HOMA‐B) of the subjects at baseline and following supplementation; mean (SD) Measurements Baseline Following supplementation Weight (kg) 95.3 (14.3) 95.8 (13.9) BMI (kg m−2) 34.2 (3.9) 34.4 (3.9) Waist (cm) 109.3 (10.3) 111.3 (8.8) Hip (cm) 119.0 (10.3) 122.0 (10.9) % body fat 40.2 (5.1) 41.2 (6.2) % lean body mass 59.8 (10.3) 58.8 (6.2) % water 44.2 (44.2) 43.6 (4.4) Systolic blood pressure (mmHg) 137.4 (21.5) 130.2 (14.6) Diastolic blood pressure (mmHg) 90.4* (11.5) 82.8* (8.9) TAG 1.4 (0.6) 1.2 (0.5) Cholesterol 5 (0.97) 4.6 (0.5) Fasting blood glucose levels (mM) 5.3 (0.3) 5.2 (0.5) Fasting insulin levels (pM) 25.3 (0.3) 23.2 (0.53) HOMA‐%S 1.0 (0.39) 0.9 (0.45) HOMA‐%B 46.4 (9.7) 45 (4.8) Figures with asterisks (*) are significantly different (P &lt; 0.05) Discussion: Supplementation with fish oils over 60 days improves a number of biomarkers used to assess risk of CVD in overweight individuals. Whilst only changes in diastolic BP were statistically significant, clinically significant reductions in all other biomarkers with positive implications for CVD risk and mortality were found. There were however a number of limitations, such as the small samples size, screening method, original glucose tolerance and insulin sensitivity of the subjects and the lack of a control group, that reduced the strength of these findings. Future, high dose, long‐term, double‐blind intervention studies controlling for these limitations would therefore be recommended.Conclusion: The findings of this pilot study show that the intake of high dose fish oil supplements over 60 days can help to reduce the risk of CHD and mortality in overweight individuals.References Diabetes UK. (2006) Guide to Diabetes [Online]. Available at http://www.diabetes.org.uk/Gdide‐to‐diabetes/Guide_to_Diabetes_Archived_pages/Insulin_resistance. Diabetes UK (accessed on December 2006).Erkkila, A., Lehto, S., Pvorala, K. &amp; Uusitupa, M. (2003) n‐3 fatty acids and 5 year risk of death and cardiovascular disease events in patients with coronary artery disease. Am. J. Clin. Nutr.78, 65–71.Zaninotto, P., Wardle, H., Stamatakis, E., Mindell, J. &amp; Head, J. (2006) Forecasting obesity to 2010; Prepared for the Department of Health: Joint Health Surveys Unit (National Centre for Social Research and Department of Epidemiology and Public Health at the Royal Free and University College Medical School).

Lipoprotein Management in Patients With Cardiometabolic Risk

Risk factors for type 2 diabetes and cardiovascular disease (CVD) often cluster, including obesity (particularly central), insulin resistance, hyperglycemia, dyslipoproteinemia, and hypertension. These conditions can also occur in isolation, and they are exaggerated by physical inactivity and smoking. Since each of these factors increases risk of CVD, the concept of global cardiometabolic risk (CMR) (Fig. 1) is of value (1). Lipoprotein abnormalities, including elevated triglycerides, low HDL cholesterol, and increased numbers of small dense LDL particles, are common findings in patients with CMR. Clinical entities with increased CMR include type 2 diabetes, familial combined hyperlipidemia, familial hypoalphalipoproteinemia, and polycystic ovary syndrome (2). These disorders often share the CMR characteristics of central obesity, insulin resistance, dyslipoproteinemia, and hypertension. There are stringent lipid treatment goals for patients with type 2 diabetes or CVD; however, guidelines for treatment of dyslipoproteinemia in high-risk subjects without diabetes or CVD are less intense and are based primarily on LDL cholesterol concentrations, with non-HDL concentrations a secondary consideration in some subjects. Numerous trials have demonstrated that therapies (primarily statins) directed at LDL cholesterol lowering clearly reduce risk of CVD events in patients with diabetes and in those without diabetes but with other CVD risk factors; yet, a number of questions remain. Even with adequate LDL cholesterol lowering, many patients on statin therapy have significant residual CVD risk. It is unclear whether lipoprotein parameters other than LDL or non-HDL cholesterol provide clinically significant additional prognostic information regarding CVD risk, yield more information about the effectiveness of therapy, or indicate more appropriate treatment targets. Many patients with CMR or diabetes have relatively normal levels of LDL cholesterol but increased numbers of small dense LDL particles and other atherogenic lipoproteins. Some have advocated that assessment of other lipoprotein parameters might be more helpful than assessment limited to LDL or non-HDL …

Long-Term Continuation on Cardiovascular Drug Treatment in Patients with Coronary Heart Disease

Combination therapy to reduce risk factors is effective in preventing recurrent cardiovascular disease events in patients with coronary heart disease (CHD), but medications need to be continued indefinitely to maximize the benefits. To evaluate the extent of long-term continuation with cardiovascular drug therapy and its expected impact on the prevention of CHD. We studied 242 patients with CHD who underwent percutaneous coronary intervention following an acute coronary syndrome over a 6 month period in 2004. We prospectively examined the extent to which specific drugs and drug combinations were continued over time by reviewing medication use at the time of hospital discharge and after 2 years. The results were used to estimate the expected loss in preventive efficacy due to discontinuation of therapy. The changes over a 2 year period in the proportions of patients taking each drug class were as follows: 15% reduction for aspirin (95% CI, -21 to -9), 10% reduction for statins (95% CI, -16 to -5), 19% reduction for angiotensin-converting enzyme inhibitors (95% CI, -26 to -12), 12% reduction for beta-blockers (95% CI, -18 to -6), 0% increase for calcium-channel blockers (95% CI, -5 to 6), 2% increase for thiazides (95% CI, -2 to 6), and 12% increase for angiotensin-II receptor blockers (95% CI, 6 to 18). The combination of aspirin, statin, and at least 2 blood pressure lowering drugs was prescribed to 81% of patients, three-quarters of whom remained on this combination after 2 years. The overall expected preventive effect on CHD of the combined medication taken during hospitalization and after 2 years was 80% and 74%, respectively. In patients with CHD, long-term continuation of combination cardiovascular drug therapy is considerably greater than generally perceived.

Glycemia Treatment Strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

There is an independent progressive epidemiologic relation between glycemia and cardiovascular disease (CVD) events; however, whether lowering glucose levels with currently available therapies can reduce CVD events remains unknown. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is designed to answer this question in high-risk patients with type 2 diabetes mellitus. In ACCORD, 10,251 patients with type 2 diabetes and other CVD risk factors or CVD were randomly allocated to intensive glycemic control, targeting a glycosylated hemoglobin (HbA1c) level <6%, or standard glycemic control, targeting an HbA1c level of 7.0%-7.9%. All participants are provided with diabetes education, glucose-monitoring equipment, and antidiabetic medications. All participants in the intensive glycemic control group are started on > or = 2 classes of agents. Doses are intensified or a new medication class is added every month if HbA1c levels are > or = 6% or if >50% of premeal or postmeal capillary glucose readings are >5.6 mmol/L (100 mg/dL) or >7.8 mmol/L (140 mg/dL), respectively. All drug combinations are permitted, and drugs are reduced only because of side effects or contraindications. Annual training, menus of approaches for intensification, regular electronic messaging, audits of achieved glycemia, and central feedback to sites support glycemic intensification strategies in intensive participants. In participants in the standard glycemic control group, therapy is intensified whenever HbA1c is > or = 8%, and antihyperglycemic drugs that promote hypoglycemia (ie, insulin or insulin secretagogues) are reduced if HbA1c persistently decreases to <7% in the setting of hypoglycemia. ACCORD addresses the hypothesis that aggressive glucose lowering prevents CVD events in patients with type 2 diabetes. It is focused on the levels of glycemia achieved using a variety of strategies, not on the specific therapies used. It will also provide information on how to safely approach near-normal levels of glucose control in clinical practice and evidence to support future clinical guidelines for diabetes management in older adults.

Rationale and Design for the Blood Pressure Intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

The Action to Control Cardiovascular Disease in Diabetes (ACCORD) blood pressure trial is an unmasked, open-label, randomized trial with a sample size of 4,733 participants. This report describes the rationale, design, and methods of the blood pressure interventions in ACCORD. Participants eligible for the blood pressure trial are randomized to 1 of 2 groups with different treatment goals: systolic blood pressure <120 mm Hg for the more intensive goal and systolic blood pressure <140 mm Hg for the less intensive goal. The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease (CVD) event, specifically nonfatal myocardial infarction or stroke, or cardiovascular death during a follow-up period ranging from 4-8 years. The ACCORD blood pressure trial should provide the first definitive clinical trial data on the possible benefit of treating to a more aggressive systolic blood pressure goal in reducing CVD events in patients with diabetes mellitus.

Prevention of Cardiovascular Disease in Persons with Type 2 Diabetes Mellitus: Current Knowledge and Rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

Patients with type 2 diabetes mellitus die of cardiovascular disease (CVD) at rates 2-4 times higher than patients without diabetes but with similar demographic characteristics. The prevalence of diabetes is increasing in the United States and, thus, the prevention of CVD in patients with diabetes poses an urgent public health challenge. The objective of this report is to review the current knowledge base for the prevention of CVD in patients with diabetes, with particular emphasis on the control of glycemia, lipids, and blood pressure. Epidemiologic analyses suggest that each 1% increase in glycosylated hemoglobin increases the risk for CVD by approximately 18%; however, evidence from the randomized trials that have examined whether glucose lowering reduces this risk is conflicting. Randomized trials have shown that lowering low-density lipoprotein cholesterol reduces CVD event rates by 17%-43% in patients with diabetes. Limited data support a role for lowering triglycerides and increasing high-density lipoprotein cholesterol in the prevention of CVD. Evidence from clinical trials shows that reducing systolic blood pressure to <140 mm Hg results in 30%-60% reductions in CVD events; however, epidemiologic evidence suggests that lowering to optimal systolic blood pressure levels (<120 mm Hg) may be additionally beneficial. Important questions regarding prevention of CVD in patients with diabetes remain unresolved, including the benefits of near-normal glycemic control, comprehensive therapy for diabetes-related dyslipidemia, and optimal blood pressure control. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial will test hypotheses to address these unanswered questions.