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OBJECTIVE--To evaluate whether in hypertensive patients the risk of cardiovascular disease is greater in association with the metabolic syndrome (MetS) or the sum of its individual components. RESEARCH DESIGN AND [...]

OBJECTIVE--The purpose of this study was to determine the baseline predictors of new-onset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk [...]

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.

Response to Tseng We agree with current recomendations (1,2) that the use of statins should be based on absolute risk rather than lipid levels. All those with diabetes and hypertension [...]

In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials.

On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke.

In previous clinical trials in high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals. As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, we aimed to investigate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size.

To determine the cardiovascular benefits of atorvastatin stratified by blood pressure-lowering regimen, 2.2 years after closure of the lipid-lowering arm (LLA) of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA).

We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial–2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke.

The NeuroThera Effectiveness and Safety Trial–1 (NEST-1) study evaluated the safety and preliminary effectiveness of the NeuroThera Laser System in the ability to improve 90-day outcomes in ischemic stroke patients treated within 24 hours from stroke onset. The NeuroThera Laser System therapeutic approach involves use of infrared laser technology and has shown significant and sustained beneficial effects in animal models of ischemic stroke.

Endothelin-1 was infused into the non-dominant brachial artery in two male subjects. We then monitored intra-arterial mean blood pressure, right atrial pressure, the heart rate and forearm blood flow (by plethysmography). Endothelin-1 at a dose of 5 x 1O-14to 5 x 1O-9mol, infused over 5 min periods, elicited no major changes in mean arterial pressure, heart rate and right atrial pressure. We observed an initial increase in forearm blood flow, followed by dose-dependent decreases of 25, 34 and 42 at 5 x 10-11to 5 x 10-9mol. A higher dose of endothelin-1, 5 x 10-8mol, given to only one of the subjects, elicited sweating and vomiting. In this subject, mean arterial pressure, right atrial pressure and the heart rate did not change, while forearm blood flow increased transiently. A deep muscular pain developed in the forearm receiving the endothelin-1 infusion after 30 min (maximum 2h, duration 10 h), and this pain was intensified by touch and muscle contractions. The force of muscle contractions in the forearm was markedly reduced and a visible oedema developed. In order to investigate the mechanisms of oedema formation, endothelin-1 (10-10to 5 x 10-8mol/l) was given intra-arterially in a rat hindquarter preparation which was perfused at a constant flow rate. In the rat, endothelin-1 increased both pre- and postcapillary resistance, leading to an increase in capillary hydrostatic pressure and a marked net transcapillary fluid transfer from the perfusate to tissue. There was no sign of increased vascular permeability. These results indicate that the development of oedema in humans may be due to an increase in capillary pressure. The similarity to sarafotoxin toxicity suggests that endothelin peptides should be tested in humans with great caution until further data on their physiological or pharmacological properties are available.

Hansson L., Hedner T., Lindhoim L., Niklason A., Luomanmaki K., Niskanen L., Lanke J., Dahlof B., de Faire U., Morlin C., Karlberg B.E., Wester P.O., Bjorck J.-E. for the CAPPP Study Group. The Captopril Prevention Project (CAPPP) in hypertension—Baseline data arid current status.The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality.The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension.The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase.The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.

Epidemiological data indicate that pulse pressure (PP) is a strong predictor of cardiovascular complications. However, correlates of PP in-patients with hypertensive LVH have not been adequately studied. We examined baseline data form 9,189 patients with hypertension and ECG LVH participating in the Losartan Intervention For End Points (LIFE) Trial. Patients were grouped as follows: PP <53 (Gr. 1,n=625), 54-63 (Gr. 2, n=1073), 64-77 (Gr. 3, n=2857) and >77 mm Hg (Gr. 4, n=4634). There was a strong positive association with several CVS risk factors and pp (table). Correlates of Pulse Pressure (pp)Gr1Gr2Gr3Gr4p-ValueAge (years)63646669<.000Systolic BP (mm Hg)147161170184<.000Cholest mmol5.936.016.026.08<.007Glucose mmol5.785.925.886.16<.000*UMA (mg/dl)47.753.255.275.4<.000**UACR4.96.45.99.5<.000LVMI (*g/m2)116121124125<.025LVMH2.752555657<.007* Urine microalbumine; ** urine albumine/creatinine ratio There was also a linear but negative association of PP with height, weight, hemoglobin level and diastolic BP (all <0.000) Conclusions: In hypertensive patients with ECG LVH PP is strongly associated with the major CVS risk factors such as age, systolic BP, serum cholesterol and glucose, microalbuminuria and degree of LVH. These associations may in part explain the predictive value of PP on cardiovascular outcomes.