Showing papers in "American Journal of Cardiology in 2003"
TL;DR: In this paper, a 6-week, parallel-group, open-label, randomized, multicenter trial was conducted to compare rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals.
Abstract: The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol ≥160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments.
1,382 citations
TL;DR: Oxidative stress in humans with coronary artery disease is also exacerbated by a reduction of vascular extracellular superoxide dismutase, normally an important protective enzyme against the superoxide anion.
Abstract: The common risk factors for atherosclerosis increase production of reactive oxygen species (ROS) by endothelial, vascular smooth muscle, and adventitial cells. These ROS initiate processes involved in atherogenesis through several important enzyme systems, including xanthine oxidase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and nitric oxide synthase. Physical forces also regulate vascular production of ROS. Oscillatory shear, which is present at sites where atherosclerosis develops, seems a particularly potent stimulus of superoxide production. The signaling cascade for activation of the NAD(P)H oxidase by angiotensin II has recently been elucidated and seems to involve a feed-forward mechanism that permits ongoing production of ROS for prolonged periods. Oxidative stress in humans with coronary artery disease is also exacerbated by a reduction of vascular extracellular superoxide dismutase, normally an important protective enzyme against the superoxide anion.
1,198 citations
TL;DR: It will be critical to define and plan therapies specifically for those patients with AF, HF, and preserved ejection fraction in addition to the population with low ejections fraction that has dominated previous investigations.
Abstract: Heart failure (HF) affects almost 5 million patients in the United States and is a leading cause of morbidity and mortality. Atrial fibrillation (AF), like HF, affects millions of patients and markedly increases in prevalence with age. As the US population ages, the number of patients afflicted with HF and AF will continue to grow. HF with preserved ejection fraction is particularly common in the elderly population. The prevalence of AF in patients with HF increases from <10% in those with New York Heart Association (NYHA) functional class I HF to approximately 50% in those with NYHA functional class IV HF. The pathophysiologic changes that occur in patients with HF and AF are complex and incompletely understood. Alterations in neurohormonal activation, electrophysiologic parameters, and mechanical factors conspire to create an environment in which HF predisposes to AF and AF exacerbates HF. Mechanisms include atrial remodeling and tachycardia-induced myopathy. The development of AF in HF appears to independently predict death resulting from pump failure and total mortality. Although the currently available therapeutic options for AF in patients with HF are varied, their effect on prognosis remains unknown and is the subject of ongoing clinical trials. It will be critical to define and plan therapies specifically for those patients with AF, HF, and preserved ejection fraction in addition to the population with low ejection fraction that has dominated previous investigations.
860 citations
TL;DR: Responses of LV reverse remodeling were associated with improvement in clinical status, cardiac function, and systolic synchronicity, and when all the above factors were put into univariate and multivariate analyses models, syStolic dyssynchrony was the only independent predictor ofreverse remodeling.
Abstract: Biventricular pacing results in left ventricular (LV) reverse remodeling in heart failure patients with wide QRS complexes. This study examines potential predictors of reverse remodeling. Echocardiography with tissue Doppler imaging was performed at baseline and 3 months after biventricular pacing in 30 patients (21 men and 9 women, mean age 62 +/- 14 years). There were 17 responders to reverse remodeling (defined as a reduction in LV end-systolic volume by >15%) and 13 nonresponders. Responders had significant improvement in 6-minute hall-walking distance (p = 0.006), metabolic equivalents (p = 0.02), peak oxygen uptake (p = 0.02), New York Heart Association functional class (p <0.001), and quality of life (p <0.001); an increase in the sphericity index (p = 0.007), ejection fraction (p <0.001), and diastolic filling time (p = 0.03); a decrease in myocardial performance index (p = 0.02), isovolumic relaxation time (p = 0.004), and mitral regurgitation (p = 0.007); and an improvement in systolic dyssynchrony (SD of the time to peak myocardial systolic contraction of the 12 LV segments as dyssynchrony index) (45.0 +/- 8.3 vs 32.5 +/- 14.5 ms, p = 0.003). In contrast, nonresponders only had a small degree of clinical improvement in New York Heart Association class (p = 0.03) and quality-of-life scores (p = 0.03), without any change in cardiac function, and worsening of systolic dyssynchrony (24.8 +/- 4.5 vs 34.1 +/- 13.5 ms, p = 0.02). When all the above factors were put into univariate and multivariate analyses models, systolic dyssynchrony was the only independent predictor of reverse remodeling (r = -0.76, p <0.001) (beta = -1.54, p = 0.007). A preimplant dyssynchrony index of 32.6 ms (+2 SDs from mean of 88 normal controls) was able to totally segregate responders from nonresponders of biventricular pacing. Thus, responders of LV reverse remodeling were associated with improvement in clinical status, cardiac function, and systolic synchronicity. Direct assessment of systolic synchronicity by tissue Doppler imaging is highly accurate in predicting responders to therapy.
665 citations
TL;DR: MR was found to be an independent predictor of mortality after multivariable analysis and present in those with ischemic and nonischemic cardiomyopathies who underwent cardiac catheterization between 1986 and 2000.
Abstract: The goal of this study was to examine the frequency of mitral regurgitation (MR) in patients with left ventricular (LV) systolic dysfunction and to relate its presence and severity to long-term survival Remodeling of the left ventricle after myocyte injury leads to a progressive change in LV size and shape, and it may lead to the development of MR The frequency of MR and its relation to survival in patients with LV systolic dysfunction has not been completely characterized We analyzed the histories, coronary anatomy, and degree of MR in patients with symptomatic heart failure and LV ejection fraction <40% who underwent cardiac catheterization between 1986 and 2000 Cox's proportional hazards modeling was used to assess the independent effect of MR on survival Two thousand fifty-seven patients met study criteria; MR was common in this cohort (562%) Of patients with MR, 811 (701%) had mild (grades 1+ or 2+) and 345 (298%) had moderate or severe (grades 3+ or 4+) regurgitation Survival rates at 1, 3, and 5 years were significantly lower in patients with moderate to severe MR versus those with mild or no MR (p <0001) MR was found to be an independent predictor of mortality after multivariable analysis (hazards ratio 123, 95% confidence interval 113 to 134, p = 00001) This relation of MR and survival was present in those with ischemic and nonischemic cardiomyopathies MR is common in patients with LV systolic dysfunction and heart failure After adjusting for other clinical variables, the presence of MR independently predicted worsened survival
623 citations
TL;DR: Periprocedural major bleeding occurs relatively frequently and is associated with adverse outcomes, and patients >80 years of age who experience intraprocedural complications are at particularly high risk.
Abstract: Bleeding related to percutaneous coronary intervention (PCI) occurs relatively frequently. We retrospectively investigated the incidence, predictors, and prognostic impact of periprocedural bleeding and transfusion in 10,974 patients who underwent PCI. Bleeding definitions were based on Thrombolysis In Myocardial Infarction (TIMI) criteria: (1) major bleeding (n = 588; 5.4%): if patients had a hemorrhagic stroke or if hematocrit decreased >15 points or by 10 to 15 points with clinical bleeding; (2) minor bleeding (n = 1,394; 12.7%): if hematocrit decreased 80 years (OR 1.9 compared with age 80 years of age who experience intraprocedural complications are at particularly high risk.
538 citations
471 citations
TL;DR: It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria, and the presence of left ventricular dyssynchrony is needed to result in improvement after cardiac resynchronization therapy.
Abstract: We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular election fraction 120 ms). The presence of left ventricular dys-synchrony is needed to result in improvement after cardiac resynchronization therapy. (C)2003 by Excerpta Medica, Inc.
450 citations
TL;DR: Interventional cardiology laboratories endeavoring to achieve the benefits of primary percutaneous coronary intervention seen in randomized clinical trials should aim to match their short door-to-balloon times.
Abstract: The mortality benefit associated with primary percutaneous coronary intervention in ST-segment elevation myocardial infarction may be lost if door-to-balloon time is delayed by >1 hour as compared with fibrinolytic therapy door-to-needle time. Interventional cardiology laboratories endeavoring to achieve the benefits of primary percutaneous coronary intervention seen in randomized clinical trials should aim to match their short door-to-balloon times.
409 citations
TL;DR: The time has come to embrace inflammation as a common pathway for atherogenic risk factors and for providing new opportunities for therapeutic intervention.
Abstract: Our current understanding of the vascular biology of atherogenesis and its clinical manifestations suggests a pathophysiology that is much more complex than mere lipid storage. Recent advances support the current view of atherosclerosis as an inflammatory process that initiates and promotes lesion development to the point of acute thrombotic complications and clinical events. Inflammatory cells localize in early-stage atherosclerotic lesions, and recent basic research has established a causal relation between inflammatory mediators or cytokines, and the steps involved in progressing from local inflammation through plaque formation. Inhibition of the action of certain specific proinflammatory cytokines, such as CD40 ligand, interferes with atherogenesis in mice. Increased circulating levels of inflammatory markers indicate increased cardiovascular risk. Thus, the time has come to embrace inflammation as a common pathway for atherogenic risk factors and for providing new opportunities for therapeutic intervention.
363 citations
TL;DR: The number of patients in group II with significant complications was higher than that in previous studies, and 57% developed either a significant aneurysm or dissection and the descending aorta diameter increased in 26% of patients.
Abstract: from their results that disappearance of the IMH suggested a good prognosis. Ide et al,6 in their series, found the descending aorta diameter (after resolution of the IMH) increased in 26% of patients. They also described 2 cases of aneurysm formation after resolution of the IMH at 1 and 27 months after initial presentation, and 1 case of dissection 1 month after hematoma resolution. The number of patients in group II with significant complications (79%) was higher than that in previous studies, and 57% developed either a significant aneurysm or dissection.7 Earlier studies may have included different acute aortic syndromes with different pathologic bases. Our study concurs with previous studies in demonstrating medical management of type B IMH (i.e., aggressive management of hypertension unless complications develop).8
TL;DR: Use of statins in patients with chronic stable CAD appears to be protective against AF, and the underlying mechanism for this effect is unknown but seems to be independent of the reduction in serum cholesterol levels.
Abstract: Atrial fibrillation (AF) is prevalent in the elderly, in patients with hypertension, and in patients with coronary artery disease (CAD). We hypothesized that statin therapy might be effective in preventing AF in patients with CAD and examined this hypothesis in a sample of patients with chronic stable CAD without AF, followed prospectively at a large outpatient cardiology practice. The association between statin use and the risk of developing AF was examined univariately and then with adjustment for potential confounding factors. Four hundred forty-nine men and women between the ages of 40 and 87 years were followed for an average of 5 years. Fifty-two patients (12%) developed AF during follow-up. Statin therapy was used by 59% of the patients during the study period and was associated with a significantly reduced risk of developing AF (crude odds ratio, 0.48, 95% confidence interval 0.28 to 0.83). This association remained significant after adjustment for potential confounders, including age, hypertension, left ventricular systolic function, occurrence of heart failure or acute ischemic events, and baseline cholesterol and changes in cholesterol levels (adjusted odds ratio 0.37, 95% confidence interval 0.18 to 0.76). Use of statins in patients with chronic stable CAD appears to be protective against AF. The underlying mechanism for this effect is unknown but appears to be independent of the reduction in serum cholesterol levels.
TL;DR: It is suggested that inflammation may link dietary fiber and fat to cardiovascular disease and subjects in the third and fourth highest quartiles of fiber consumption had a lower risk of elevated CRP.
Abstract: We examined the relation of dietary fiber, fat, and other dietary factors to levels of highly sensitive C-reactive protein (CRP) in 4,900 adult participants in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES 99-00), which was a cross-sectional study of a nationally representative sample of noninstitutionalized United States residents. After controlling for demographic factors, body mass index, smoking, alcohol consumption, exercise, and total caloric intake, subjects in the third and fourth highest quartiles of fiber consumption had a lower risk of elevated CRP (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.43 to 0.96; OR 0.58, 95% CI 0.38 to 0.88, respectively) compared with the lowest quartile. Saturated fat consumption was modestly associated with elevated CRP (third quartile: OR 1.58, 95% CI 1.02 to 2.44; fourth quartile 1.44, 95% CI 0.80 to 2.58). The findings suggest that inflammation may link dietary fiber and fat to cardiovascular disease.
TL;DR: The findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease, and CRP had a weaker association with cardiovascular disease than the cytokines.
Abstract: This study investigates the association of several inflammatory markers with subclinical and clinical cardiovascular disease in older men and women. Data are from the baseline assessment of 3,045 well-functioning persons aged 70 to 79 years, participating in the Health, Aging and Body Composition study. The study sample was divided into 3 groups: "cardiovascular disease" (diagnosis of congestive heart failure, coronary artery disease, peripheral artery disease, or stroke), "subclinical cardiovascular disease" (positive findings on the Rose questionnaire for angina or claudication, ankle-brachial index <0.9, or electrocardiographic abnormalities), and "no cardiovascular disease." Serum levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and the soluble receptors IL-6 soluble receptor, IL-2 soluble receptor, TNF soluble receptor I, and TNF soluble receptor II were assessed. Of those with IL-6 levels in the highest compared with the lowest tertile, the odds ratio (OR) for subclinical cardiovascular disease was 1.58 (95% confidence interval [CI] 1.26 to 1.97) and for clinical cardiovascular disease was 2.35 (95% CI 1.79 to 3.09). A similar association was found for TNF-alpha (OR 1.48, 95% CI 1.16 to 1.88 and OR 2.05, 95% CI 1.55 to 2.72, respectively). In adjusted analyses, CRP was not significantly associated with overall subclinical or clinical cardiovascular disease, although additional analyses did find a strong specific association between CRP and congestive heart failure (OR 1.64, 95% CI 1.11 to 2.41). Of the soluble cytokine receptors, only TNF soluble receptor I showed a significant association with clinical cardiovascular disease. Thus, our findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease. In this study, CRP had a weaker association with cardiovascular disease than the cytokines.
TL;DR: The thiazolidinediones are peroxisome proliferator-activated receptor-gamma agonists that improve glucose and lipid metabolism that have recently been shown to improve endothelial function in the early stages of insulin resistance.
Abstract: The endothelium regulates vascular tone through the release of vasodilating and vasoconstricting substances. The most important of these vasodilating substances is nitric oxide (NO), which is also vascular protective and inhibits inflammation, oxidation, vascular smooth muscle cell proliferation, and migration. Damage to the endothelium causes endothelial dysfunction with impaired release of NO and loss of its antiatherogenic protection. Traditional risk factors for coronary artery disease, including diabetes, hypercholesterolemia, hypertension, and low levels of high-density lipoprotein cholesterol, are associated with endothelial dysfunction and thus promote the atherogenic process. More recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome has been associated with endothelial dysfunction. This association provides evidence that the atherosclerotic process may actually begin earlier in the spectrum of insulin resistance, ultimately resulting in a progression of the metabolic syndrome to prediabetes and then to type 2 diabetes. Aggressive treatment of dyslipidemia and hypertension, even before the onset of type 2 diabetes, would appear prudent in decreasing the progression of the atherosclerotic process. The thiazolidinediones are peroxisome proliferator-activated receptor–γ agonists that improve glucose and lipid metabolism. These agents have recently been shown to improve endothelial function in the early stages of insulin resistance. Results from ongoing trials with thiazolidinediones will reveal whether they will also reduce cardiovascular end points.
TL;DR: The Insulin Resistance Atherosclerosis Study found that insulin resistance, as determined by a frequently sampled glucose tolerance test, is significantly related to higher CRP levels, higher fibrinogen, and higher plasminogen activator inhibitor-1 (PAI-1) levels, which are predictors of the development of type 2 diabetes.
Abstract: Type 2 diabetes is associated with a marked increase in the incidence of coronary artery disease (CAD); however, the correlation between glycemia and CAD in patients with type 2 diabetes is only modestly positive This relatively weak association between glycemia and CAD in subjects with diabetes may be caused by the existence of an atherogenic prediabetic state In the San Antonio Heart Study, subjects who start with normal glucose tolerance and later develop type 2 diabetes have increased triglyceride levels, increased systolic blood pressure, and decreased levels of high-density lipoprotein cholesterol before the onset of type 2 diabetes The basis for these atherogenic prediabetic changes may be related to insulin resistance rather than reduced insulin secretion Recently, interest has focused on a possible role of fibrinolysis and increased subclinical inflammation, as determined by high-sensitivity C-reactive protein (CRP) levels The Insulin Resistance Atherosclerosis Study found that insulin resistance, as determined by a frequently sampled glucose tolerance test, is significantly related to higher CRP levels, higher fibrinogen, and higher plasminogen activator inhibitor-1 (PAI-1) levels The investigators also have shown that high PAI-1 and CRP levels are predictors of the development of type 2 diabetes In addition, the Women's Health Study has shown that high CRP levels predict type 2 diabetes Insulin-sensitizing interventions have been demonstrated to reduce these nontraditional risk factors Rosiglitazone, an agent with insulin-sensitizing properties, decreases PAI-1 and CRP levels Some of the adverse cardiovascular effects seen in patients with type 2 diabetes may be reversed by insulin-sensitizing agents
TL;DR: It is shown that there are important differences in the performance of BNP versus NT-proBNP in monitoring patients with congestive heart failure that need to be further explored.
Abstract: Given the limitations of low enrollments, this study suggests that a change of 130% for B-type natiuretic peptide (BNP) and 90% for N-terminal (NT)-proBNP are necessary before results of serially collected data can be considered statistically different. This study also shows that there are important differences in the performance of BNP versus NT-proBNP in monitoring patients with congestive heart failure that need to be further explored.
TL;DR: It is demonstrated that the use of statins in patients with lone AF was associated with a significant decrease in the risk of arrhythmia recurrence after successful cardioversion.
Abstract: The aim of this study was to investigate the effect of statin therapy on arrhythmia recurrence in patients with lone atrial fibrillation (AF). From July 1998 to December 1999, 62 patients with lone persistent AF lasting ≥3 months underwent successful external cardioversion. After a mean follow-up of 44 months, 85% had recurrence of AF. The use of statins was associated with a significant decrease in the risk of arrhythmia recurrence after successful cardioversion of AF. The result of this retrospective study demonstrates that the use of statins in patients with lone AF was associated with a significant decrease in the risk of arrhythmia recurrence after successful cardioversion.
TL;DR: A JUPITER trial is planned to examine the effects of rosuvastatin treatment in preventing cardiovascular events in 15,000 healthy subjects with elevated hs-CRP levels in the absence of overt hyperlipidemia.
Abstract: Inflammation is a major factor in atherothrombotic disease. Levels of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Recent findings in 27,939 healthy women in the Women's Health Study indicate that hs-CRP (1) is a stronger predictor of risk than low-density lipoprotein (LDL) cholesterol, (2) predicts elevated risk in subjects without overt hyperlipidemia, and (3) adds prognostic information to risk scoring and LDL cholesterol categories. Other data from this cohort show that hs-CRP level adds prognostic information to the diagnosis of the metabolic syndrome. Taken together with other data in men on the association of hs-CRP with vascular risk, a strong argument is provided for screening in the primary prevention population. With regard to potential treatment, statins have been found to reduce hs-CRP levels, and data from statin treatment trials raise the possibility that subjects with elevated hs-CRP levels may derive greater benefit from treatment than do patients without elevated hs-CRP. The Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial is planned to examine the effects of rosuvastatin treatment in preventing cardiovascular events in 15,000 healthy subjects with elevated hs-CRP levels in the absence of overt hyperlipidemia.
TL;DR: Depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.
Abstract: The ENRICHD clinical trial, which compared an intervention for depression and social isolation to usual care, failed to decrease the rate of mortality and recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation for this is that depression was not associated with increased mortality in these patients. The purpose of this study was to determine if depression was associated with an increased risk of mortality in a subsample of the ENRICHD trial's depressed patients compared with a group of nondepressed patients recruited for an ancillary study. Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months. There were 47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk factors, depressed patients were at higher risk for all-cause mortality (hazard ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with nondepressed patients. In conclusion, depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.
TL;DR: It is demonstrated that lower baseline hemoglobin is associated with risk of short-term adverse clinical outcomes in this population of patients with decompensated heart failure, even after controlling for other baseline differences.
Abstract: We investigated the prevalence of anemia and its relation to clinical events in patients with decompensated heart failure enrolled in the OPTIME-CHF study. Our data demonstrate that anemia is common in patients hospitalized with decompensated heart failure and is associated with a greater number of co-morbid conditions. Lower baseline hemoglobin is associated with risk of short-term adverse clinical outcomes in this population, even after controlling for other baseline differences.
TL;DR: Potential mechanism by which ACE inhibition reduces the development of diabetes, improves these surrogate markers, and reduces cardiovascular disease and renal disease is explored.
Abstract: Angiotensin-converting enzyme (ACE) inhibitors are the first-line therapeutic agents for treating hypertension in patients with the cardiometabolic syndrome and those with diabetes. ACE inhibitor therapy reduces both microvascular and macrovascular complications in diabetes and appears to improve insulin sensitivity and glucose metabolism. Several recent studies indicate that ACE inhibitor therapy reduces the development of type 2 diabetes in persons with essential hypertension, a population with a high prevalence of insulin resistance. ACE inhibitor therapy has been shown to improve surrogates of cardiovascular disease (eg, vascular compliance, endothelial-derived nitric oxide production, vascular relaxation and plasma markers of inflammation, oxidative stress, and thrombosis) and reduce cardiovascular disease, renal disease progression, and stroke. This article explores potential mechanism by which ACE inhibition reduces the development of diabetes, improves these surrogate markers, and reduces cardiovascular disease and renal disease.
TL;DR: Tissue Doppler imaging allows assessment of left ventricular dyssynchrony and resynchronization after biventricular pacing.
Abstract: Tissue Doppler imaging allows assessment of left ventricular dyssynchrony and resynchronization after biventricular pacing.
TL;DR: Plasma apoB and the various cholesterol indexes are complementary rather than competitive indexes of atherosclerotic risk and provide further evidence as to why measurement of apiB should be part of a standard lipoprotein assessment of CAD risk.
Abstract: The objective of the present study was to examine concordance/discordance among 4 atherogenic indexes of cardiovascular risk: plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, and apolipoprotein B-100 (apoB). Analyses were conducted in a cohort of 2,103 men without coronary artery disease (CAD) at the onset of the Quebec Cardiovascular Study. Although there were strong and highly significant correlations among the 4 risk indexes (0.78 1/3 of all subjects had discordant levels. Kappa analysis confirmed that there was only fair agreement between apoB and total or LDL cholesterol (0.38 and 0.36, respectively) and only moderate agreement between non-HDL cholesterol and apoB (0.47). Finally, a significant proportion of subjects (528 of 2,103) who had disproportionately higher apoB levels than would have been predicted based on their LDL cholesterol concentrations was more obese and manifested several features of the metabolic syndrome. They also had a significantly increased cardiovascular risk. In summary, plasma apoB and the various cholesterol indexes are complementary rather than competitive indexes of atherosclerotic risk and provide further evidence as to why measurement of apoB should be part of a standard lipoprotein assessment of CAD risk.
TL;DR: Ezetimibe plus Lovastatin was well tolerated, with a safety profile similar to both lovastatin alone and placebo, and may offer a new treatment option in lipid management of patients with hypercholesterolemia.
Abstract: This multicenter, randomized, double-blind, placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week single-blind placebo lead-in period, 548 patients with low-density lipoprotein (LDL) cholesterol ≥145 mg/dl (3.75 mmol/L) and ≤250 mg/dl (6.47 mmol/L) and triglycerides ≤350 mg/dl (3.99 mmol/L) were randomized to one of the following, administered daily for 12 weeks: ezetimibe 10 mg; lovastatin 10, 20, or 40 mg; ezetimibe 10 mg plus lovastatin 10, 20, or 40 mg; or placebo. The primary efficacy variable was percentage decrease in direct LDL cholesterol from baseline to end point for pooled ezetimibe plus lovastatin versus pooled lovastatin alone. Ezetimibe plus lovastatin significantly improved concentrations of LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides compared with lovastatin alone (p <0.01). The coadministration of ezetimibe provided an incremental 14% LDL cholesterol decrease, a 5% HDL cholesterol increase, and a 10% decrease in triglycerides compared with pooled lovastatin alone. Ezetimibe plus lovastatin provided mean LDL cholesterol decreases of 33% to 45%, median triglyceride decreases of 19% to 27%, and mean HDL cholesterol increases of 8% to 9%, depending on the statin dose. The coadministration of ezetimibe 10 mg plus the starting dose of lovastatin (10 mg) provided comparable efficacy to high-dose lovastatin (40 mg) across the lipid profile (LDL cholesterol, HDL cholesterol, and triglycerides). Ezetimibe plus lovastatin was well tolerated, with a safety profile similar to both lovastatin alone and placebo. The coadministration of ezetimibe and lovastatin may offer a new treatment option in lipid management of patients with hypercholesterolemia.
TL;DR: Data suggest that statin-induced alterations in the function of small G proteins may contribute to the anti-inflammatory and antithrombotic actions of statins in clinical practice.
Abstract: The traditional view of cardiovascular disease held that the degree of stenosis defined high-risk lesions and that removal of cholesterol shrank these lesions and thereby enlarged the lumen. Advances in understanding of the pathophysiology of the acute coronary syndromes refute this view. We now appreciate that vascular biology determines plaque stability and that statins stabilize plaque by favorably altering this biology. They do so chiefly (but probably not exclusively) by cholesterol lowering. In addition to reducing the cholesterol content of plaque, lipid lowering inhibits inflammation, and decreases collagenolytic activity and thrombotic potential. The role of lipid-independent effects remains unclear because many studies used statin concentrations too high to have any clinical relevance. However, data suggest that statin-induced alterations in the function of small G proteins may contribute to the anti-inflammatory and antithrombotic actions of statins in clinical practice.
TL;DR: The prototype of this new therapeutic class of PDE5 inhibitors is sildenafil, which was approved for treatment of erectile dysfunction in 1998, and Tadalafil and vardenafil are new agents in this class.
Abstract: Since the early 1980s, research on the mechanisms of penile erection has done much to clarify erectile physiology and pathophysiology. More recent studies have identified the importance of neurochemical mediators in erection. These include the nitric oxide-cyclic guanosine monophosphate (cGMP) cell-signaling system-a complex molecular pathway that mediates smooth muscle relaxation in the corpus cavernosum. Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Inhibition of PDE5 is expected to enhance penile erection by preventing cGMP degradation. Development of pharmacologic agents with this effect has closely paralleled the emerging science. The prototype of this new therapeutic class of PDE5 inhibitors is sildenafil, which was approved for treatment of erectile dysfunction in 1998. Tadalafil and vardenafil are new agents in this class. These agents have demonstrated improvement in erectile function and have been shown to be well tolerated in diverse populations comprising thousands of men worldwide. Profiles of these 3 PDE5 inhibitors are reviewed herein.