Cardiovascular Events

This study was designed to determine the predictive value of lipid hydroperoxide (LOOH) levels for adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD). Oxidative modification of circulating lipids contributes to inflammation and endothelial dysfunction, which are hallmark features of atherosclerosis. A serum biomarker of oxidation is LOOH, which is a primary product of fatty acid peroxidation. Serum LOOH levels were measured and correlated with clinical events over a 3-year period in 634 patients with angiographic evidence of CAD. Baseline LOOH levels in the highest quartile were associated with hazard ratios of 3.24 (95% confidence interval [CI] 1.86 to 5.65; p = 0.0001) for nonfatal vascular events (n = 149), 1.80 (95% CI 1.13 to 2.88; p = 0.014) for major vascular procedures (n = 139), and 2.23 (95% CI 1.44 to 3.44; p = 0.0003) for all vascular events and procedures. Baseline LOOH levels correlated with serum levels of soluble intercellular adhesion molecule-1 (p = 0.001) and thiobarbituric acid reactive substances (p = 0.001) as well as the mean percent change in stenosis for large segments >50% stenosed (p = 0.048). A multivariate proportional hazards model, adjusted for traditional risk factors and inflammatory markers, showed an independent effect of LOOH on nonfatal vascular events, vascular procedures, and all events or procedures. Amlodipine treatment was associated with reduced cardiovascular events and changes in LOOH levels compared with placebo. Elevated LOOH levels were predictive of nonfatal vascular events and procedures in patients with stable CAD, independent of traditional risk factors and inflammatory markers.

Results: Serum uric acid and C-reactive protein levels were significantly decreased in subjects treated with allopurinol. In the control group, eGFR decreased 3.3 ± 1.2 ml/min per 1.73 m 2 , and in the allopurinol group, eGFR increased 1.3 ± 1.3 ml/min per 1.73 m 2 after 24 ...

Numerous local interventions for cardiovascular disease are available, but resources to deliver them are limited. Identifying the most effective interventions is challenging because cardiovascular risks develop through causal pathways and gradual accumulations that defy simple calculation. We created a simulation model for evaluating multiple approaches to preventing and managing cardiovascular risks. The model incorporates data from many sources to represent all US adults who have never had a cardiovascular event. It simulates trajectories for the leading direct and indirect risk factors from 1990 to 2040 and evaluates 19 interventions. The main outcomes are first-time cardiovascular events and consequent deaths, as well as total consequence costs, which combine medical expenditures and productivity costs associated with cardiovascular events and risk factors. We used sensitivity analyses to examine the significance of uncertain parameters. A base case scenario shows that populatio...

Background— Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown. Methods and Results— MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (>350 μg/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P =0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 μg/L (adjusted HR 7.48 [95% CI 1.98 to ...

Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene increase susceptibility to hypertension and cardiovascular disease. We examined genetic and pharmacogenetic associations between NOS3 polymorphisms, blood pressure (BP) control, and cardiovascular events in elderly, hypertensive coronary artery disease (CAD) patients. Patients with CAD were randomly assigned to either verapamil SR- or atenolol-based antihypertensive treatment and followed for cardiovascular events. Cases (all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke) and an age-, sex-, race/ethnicity-matched control population were genotyped for the -786T>C and Glu298>Asp polymorphisms in NOS3. On-treatment BP and BP control were compared across genotype groups. Logistic regression was performed to estimate odds ratios (ORs) for the -786T>C and Glu298>Asp polymorphisms in the combined population and in randomized treatment groups. Genotype data were available for 256 cases and ...

Patients with type 2 diabetes mellitus (DM) have a marked increase in the risk of myocardial infarction (MI), and a substantially worse prognosis after MI compared with patients without diabetes. 1-3 In recent years, it has become apparent that optimal control of blood pressure and low-density lipoprotein cholesterol (LDL-C) level can substantially reduce excess cardiovascular risk in patients with diabetes.

Mineralocorticoid receptor (MR) activation stimulates systemic vascular and left ventricular remodeling. We hypothesized that MR contributes to pulmonary vascular and right ventricular (RV) remodeling of pulmonary hypertension (PH). We evaluated the efficacy of MR antagonism by spironolactone in two experimental PH models; mouse chronic hypoxia-induced PH (prevention model) and rat monocrotaline-induced PH (prevention and treatment models). Last, the biological function of the MR was analyzed in cultured distal pulmonary artery smooth muscle cells (PASMCs). In hypoxic PH mice, spironolactone attenuated the increase in RV systolic pressure, pulmonary arterial muscularization, and RV fibrosis. In rat monocrotaline-induced PH (prevention arm), spironolactone attenuated pulmonary vascular resistance and pulmonary vascular remodeling. In the established disease (treatment arm), spironolactone decreased RV systolic pressure and pulmonary vascular resistance with no significant effect on h...

The prognostic significance of ambulatory blood pressure (ABP) has not been established in patients with type 2 diabetes (T2DM). In order to clarify the impact of ABP on cardiovascular prognosis in patients with or without T2DM, we performed ABP monitoring (ABPM) in 1,268 subjects recruited from nine sites in Japan, who were being evaluated for hypertension. The mean age of the patients was 70.4 +/- 9.9 years, and 301 of them had diabetes. The patients were followed up for 50 +/- 23 months. We investigated the relation between incidence of cardiovascular diseases (CVDs) and different measures of ABP, including three categories of awake systolic blood pressure (SBP <135, 135-150, and >150 mm Hg), sleep SBP (<120, 120-135, and >135 mm Hg), and dipping trends in nocturnal blood pressure (BP) (dippers, nondippers, and risers). Cox regression models were used in order to control for classic risk factors. Higher awake and sleep SBPs predicted higher incidence of CVD in patient...

Chronic obstructive pulmonary disease (COPD) is a risk factor for development of cardiovascular events, independent of smoking. The mechanisms are unclear, but systemic inflammation associated with COPD may contribute to this cardiovascular risk. Similar to cigarette smoking, exposure to particulate air pollution is associated with an increase in the mortality and morbidity from respiratory and cardiovascular diseases. The exposure of humans to high levels of ambient particles stimulates the bone marrow and the release of neutrophils, band cells, and monocytes into the circulation. This bone marrow simulation is associated with increased levels of circulating interleukin-1beta and interleukin-6, similar to cigarette smoking. In animals, exposure to particulate matter accelerates the transit of neutrophils and monocytes in bone marrow and expands the leukocyte pool size. This systemic inflammatory response to particle inhalation causes endothelial activation and upregulation adhesion...

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations w...

BACKGROUND: Cycloset™ is a quick-release formulation of bromocriptine mesylate, a dopamine agonist, which in animal models of insulin resistance and type 2 diabetes acts centrally to reduce resistance to insulin- mediated suppression of hepatic glucose output and tissue glucose disposal. In such animals, bromocriptine also reduces hepatic triglyceride synthesis and free fatty acid mobilization, manifesting decreases in both plasma triglycerides and free fatty acids. In clinical trials, morning administration of Cycloset™ either as monotherapy or adjunctive therapy to sulfonylurea or insulin reduces HbA1c levels relative to placebo by 0.55–1.2. Cycloset™ therapy also reduces plasma triglycerides and free fatty acid by approximately 25% and 20%, respectively, among those also receiving sulfonylurea therapies. The effects of once-daily morning Cycloset™ therapy on glycemic control and plasma lipids are demonstrable throughout the diurnal portion of the day (7 a.m. to 7 p.m.) across pos...

BACKGROUND: Hypertension is among the most common chronic condition in middle-aged and older adults. Approximately 50 million Americans are currently diagnosed with this condition, and more than $18.7 billion is spent on hypertension management, including $3.8 billion for medications. There are numerous pharmacological agents that can be chosen to treat hypertension by physicians in clinical practices. The purpose of this study was to assess the cost of alternative antihypertensive treatments in older adults with isolated systolic hypertension (ISH). METHOD: Using the Systolic Hypertension in the Elderly Program (SHEP) and other data, a cost-minimization analysis was performed. The cost was presented as the cost of number-needed-to treat (NNT) of patients for 5 years to prevent one adverse event associated with cardiovascular disease (CVD). RESULT: It was found that the cost of 5 year NNT to prevent one adverse CVD event ranged widely from $6,843 to $37,408 in older patients with IS...