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Background: Reduction of electrocardiographic left ventricular hypertrophy (LVH) has been associated with decreased cardiovascular death, stroke, myocardial infarction, and atrial fibrillation. However, whether reduction of electrocardiographic LVH is associated with decreased heart failure is unclear. Objective: To examine the relation of reduction of electrocardiographic LVH to incident heart failure. Design: Multicenter cohort study derived from a randomized, controlled trial. Setting: Losartan Intervention For Endpoint reduction in hypertension study. Patients: 8479 hypertensive patients without history of heart failure who were randomly assigned to losartan or atenolol treatment. Measurements: Change in Cornell product electrocardiographic LVH between baseline and in-study electrocardiograms, examined as both a continuous variable and a dichotomous variable (above or below the median decrease of 236 mm x msec) to predict heart failure hospitalization occurring after the 6-month follow-up visit. Results: During mean follow-up of 4.7 years (SD, 1.1 years), 214 patients were hospitalized for heart failure (2.5%): 77 patients with an in-treatment decrease of 236 mm x msec or more (4.4 per 1000 patient-years) and 137 patients with a reduction less than 236 mm x msec during treatment (6.8 per 1000 patient-years). In a univariate Cox analysis in which change in Cornell product was treated as a time-varying continuous variable, decrease in Cornell product during treatment was associated with a decreased risk for new-onset heart failure, with a 24% lower risk for heart failure for every 817-mm x msec (1 SD of the mean) lower Cornell product (hazard ratio, 0.76 [95% CI, 0.72 to 0.80]). In a parallel analysis in which change in Cornell product was entered as a time-varying dichotomous variable, a greater-than-median in-treatment decrease in Cornell product (236 mm x msec) was associated with a 43% lower risk for heart failure (hazard ratio, 0.57 [CI, 0.44 to 0.76]). After adjustment for treatment, baseline risk factors for heart failure, baseline and in-treatment blood pressure, and baseline severity of electrocardiographic LVH, in-treatment decrease of Cornell product LVH in time-varying multivariate Cox models remained strongly associated with new heart failure hospitalization, with a 19% lower risk for every 817-mm x msec lower Cornell product treated as a continuous variable (hazard ratio, 0.81 [CI, 0.77 to 0.85]) or a 36% decreased rate of new heart failure in patients with an in-treatment reduction in Cornell product of 236 mm x msec or more (hazard ratio, 0.64 [CI, 0.47 to 0.89]; P < 0.001 for all comparisons). Limitations: Use of electrocardiographic LVH to select patients may have increased risk compared with unselected hypertensive patients, and use of hospitalization for heart failure as the end point will underestimate the incidence of new heart failure. Conclusion: Reduction in Cornell product electrocardiographic LVH during antihypertensive therapy is associated with fewer hospitalizations for heart failure, independent of blood pressure lowering, treatment method, and other risk factors for heart failure.

OBJECTIVE--Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to [...]

OBJECTIVE--This study aims to establish the benefits of lowering cholesterol in diabetic patients with well-controlled hypertension and average/below-average cholesterol concentrations, but without established coronary disease. RESEARCH DESIGN AND METHODS--In the [...]

Background: Several studies have shown that albuminuria is associated with increased risk for fatal and nonfatal cardiovascular events, independent of conventional risk factors. The partition values for urine albumin-creatinine ratio (UACR) used to identify microalbuminuria have been based on studies that predicted risk in diabetic patients. Objective: To determine whether the relation between albuminuria and cardiovascular risk can be used to predict cardiovascular morbidity and mortality in hypertensive patients. Design: Multicenter cohort study derived from a randomized, controlled trial. Patients: 8206 patients with stage II or III hypertension randomly assigned to double-blind therapy with losartan or atenolol. Follow-up was 39 122 patient-years. Measurements: Renal glomerular permeability evaluated by UACR. Results: In nondiabetic hypertensive patients with left ventricular hypertrophy, the risk for the composite cardiovascular end point increased continuously as albuminuria increased (P < 0.001 for trend.) There was no specific threshold for increased risk. For every 10-fold increase in UACR, hazard ratios in nondiabetic patients increased as follows: composite end point, by 57% (95% CI, 40.6% to 75.0%); cardiovascular mortality, by 97.7% (CI, 66.5% to 235%); all-cause mortality, by 75.2% (CI, 54.0% to 99.4%); stroke, by 51.0% (CI, 28.8% to 76.9%); and myocardial infarction, by 45% (CI, 19.9% to 75.4%) (P < 0.001 for all comparisons). Values were similar in diabetic patients, although for myocardial infarction the trend was weaker and not significant. Conclusion: Increased UACR resulted in increasing risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy. We found no thresholds or plateaus. Risk increases at much lower UACR values than has been reported among diabetic patients.

Background: Cardiovascular morbidity and mortality are reduced by treatment with the angiotensin II AT(sub 1)-receptor antagonist losartan compared with conventional treatment with the beta-blocker atenolol in patients with hypertension and electrocardiogram-defined left ventricular hypertrophy, many of whom had known vascular disease. Objective: To determine whether losartan reduces cardiovascular event rates in lower-risk hypertensive patients without clinically evident vascular disease. Design: Subgroup analysis or a randomized trial. Setting: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Patients: 6886 men and women (57% women) 55 to 80 years of age (average, 66 years) with essential hypertension (sitting blood pressure, 160 to 200/95 to 115 mm Hg [average, 174/98 mm Hg]) and electrocardiogram-defined left ventricular hypertrophy who did not have clinically evident vascular disease. Intervention: Patients were randomly assigned to once-daily double-blind treatment with losartan or atenolol. Measurements: An end point committee ascertained end points (cardiovascular death, stroke, or myocardial infarction). Results: Blood pressure was reduced similarly by losartan and atenolol. The primary composite end point occurred in 282 losartan-treated patients (17.5 per 1000 patient-years) and 355 atenolol-treated patients (21.8 per 1000 patient-years; relative risk, 0.81 [95% CI, 0.69 to 0.95]; P=0.008). Cardiovascular death occurred in 103 losartan-treated patients and 132 atenolol-treated patients (relative risk, 0.80 [CI, 0.62 to 1.04]; P=0.092), stroke (nonfatal and fatal) occurred in 125 losartan-treated patients and 193 atenolol-treated patients (relative risk, 0.66 [CI, 0.53 to 0.82]; P0.2). New onset diabetes occurred less often in patients treated with losartan (n=173) than in patients treated with atenolol (n=254) (relative risk, 0.69 [CI, 0.57 to 0.84]; P

Introduction:Targeting the human platelet for prevention of occlusive thrombotic events remains an active area of research due to the high incidence of myocardial infarction and stroke due to platelet-rich thrombotic clots. While, many patients taking FXa anticoagulant therapy require further inhibition of thrombosis, dual therapy including anticoagulant plus antiplatelet drugs result in an increased risk for bleeding. The current study sought to determine if a histone deacetylase (HDAC) inhibitor, either alone or in combination with the FXa inhibitor rivaroxaban, is able to effectively inhibit platelet and fibrin formation at the site of vascular injury without causing a significant increase in the bleeding risk in mice.

Anti-platelet therapeutics are common tools in the treatment of thrombotic diseases, decreasing morbidity and mortality resulting from cardiovascular complications. However, many patients remain at risk for a cardiovascular event while others experience bleeding due to hemostatic dysregulation. The need for target specificity and lasting stability presents a major challenge in the development of novel antithrombotic therapeutics. While increasing platelet cAMP levels through activation of the prostacyclin (IP) receptor is a viable therapeutic approach, the IP receptor is currently considered a challenging target due to the non-selectivity and instability of existing IP agonists. Our lab has developed a novel IV and orally available IP receptor agonist, CS585, with selectivity towards the IP receptor and sustained in vivoprotection from injury-induced thrombosis without observed bleeding. CS585 demonstrates IP receptor-dependent activity, leading to activation of protein kinase A (PKA), a key player in inhibitory signaling. While indications of current IP receptor agonists are limited to pulmonary arterial hypertension and temporary relief of peripheral artery disease, CS585 presents a new approach to selectively regulate platelet activation and thrombosis.