Niacin and laropiprant.

Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to modestly lowering low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a), niacin is currently the most effective available agent for raising high-density lipoprotein cholesterol (HDL-C). Despite its well-documented beneficial effects on lipids, the clinical use of niacin has been limited by its side effect profile, notably flushing. This sensation of cutaneous vasodilatation and burning has limited patient compliance and is a frequent cause of discontinuation of the drug. While pretreatment with nonsteroidal anti-inflammatory agents, such as aspirin, may reduce the incidence of flushing, present-day niacin still results in flushing in many patients. Recent studies have elucidated what we currently understand as the molecular mechanism that mediates niacin-induced flushing, specifically that niacin acting through its receptor stimulates the production of several prostaglandins, including prostaglandin (PG) I(2), PGE(2) and PGD(2). Laropiprant is a potent, highly selective prostaoid DP(1) receptor antagonist that decreases the incidence and intensity of niacin-induced flushing without affecting its beneficial lipid effects. Thus, laropiprant, when used in conjunction with niacin, can improve the tolerability of niacin and aid in medication compliance. This paper reviews the data suggesting the importance of raising HDL with niacin, describes the pharmacology of the drug, and examines the potential beneficial effects of combining niacin with laropiprant.

Carotid artery stiffness, high-density lipoprotein cholesterol and inflammation in men with pre-hypertension.

Low circulating levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk for cardiovascular events. HDL-C has a variety of poorly understood atheroprotective effects, including altering lipid metabolism and reducing inflammation. Increased arterial stiffness is an important predictor of subsequent cardiovascular risk. Therefore, in this study, we sought to determine whether HDL-C levels are associated with carotid arterial stiffness. In addition, we examined potential correlates of this association, such as inflammatory factors, cardiorespiratory fitness and body fat percentage. Carotid artery beta-stiffness was measured by ultrasound in 47 (23 years old) healthy pre-hypertensive men. Low HDL-C was defined as <1.0 mmol l(-1). Body fat was measured by air displacement plethysmography. Cardiorespiratory fitness was measured using a maximal exercise test, with metabolic gas analysis and inflammatory markers consisting of C-reactive protein (CRP), white blood cell (WBC) count and absolute neutrophil count. Men with a low HDL-C had significantly higher carotid artery stiffness, CRP, WBC count, neutrophil count, body fat, fasting glucose and lower cardiorespiratory fitness (P<0.05). Co-varying for cardiorespiratory fitness, % body fat and glucose had no effect on group differences in carotid artery stiffness. Co-varying for inflammatory markers resulted in groups having similar carotid artery stiffness. Pre-hypertensive men with low HDL-C have a higher carotid artery stiffness when compared with those with higher HDL-C. The detrimental effects of low HDL-C on large artery stiffness in pre-hypertensive men may be mediated by inflammation and not by cardiorespiratory fitness or body fat levels.

Low levels of high-density lipoprotein cholesterol are associated with vascular remodeling in cardiac transplant recipients.

BACKGROUND: Early atherosclerosis may be associated with compensatory vessel enlargement, termed positive remodeling. Enlarged brachial artery diameter has been reported in patients with risk factors for atherosclerosis and in individuals with coronary atherosclerosis, indicating that brachial artery enlargement is a marker for the presence of atherosclerotic changes. Cardiac transplant recipients often have abnormal lipid levels, but the effect of specific lipid abnormalities on vascular remodeling in this population has not been evaluated. This study examined the relationship between lipid levels and brachial artery diameter in cardiac transplant recipients. METHODS: Thirty-five stable cardiac transplant recipients underwent high-resolution brachial artery ultrasound to evaluate resting brachial artery diameter. Levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were determined and the presence of other cardiac risk factors was assessed. RESULTS: Brachial artery diameter was larger (4.3 +/- 0.1 mm) in subjects with low levels of HDL-C (< 40 mg/dL, n = 11) compared to subjects with high HDL-C (> or = 40 mg/dL, n = 24), who had a mean brachial artery diameter of 3.7 +/- 0.1 mm (P = .006). Neither high LDL-C (> or = 100 mg/dL) nor high triglycerides (> or = 200 mg/dL) were associated with differences in brachial artery diameter. Multivariate analysis demonstrated that the relationship between low HDL-C and increased brachial artery diameter was independent of body surface area or statin use. CONCLUSIONS: Low levels of HDL-C are an independent predictor of brachial artery enlargement in stable cardiac transplant recipients. These findings suggest that suboptimal HDL-C levels may be associated with the development of vascular remodeling and atherosclerosis in this population.

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease.

OBJECTIVES: We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI). BACKGROUND: Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV. METHODS: Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline. RESULTS: Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02). CONCLUSIONS: Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Benign lipid envelope of the heart simulating a pericardial hematoma.

The hallmark of diagnosing a pericardial effusion by echocardiography is the presence of relatively sonolucent space outside of the cardiac structures. The location, size, mobility, and consistency of the pericardial space determined by echocardiography are considered to be reliable markers for defining pericardial processes. In certain clinical scenarios, however, it may be difficult to differentiate fluid from other pericardial processes, notably subepicardial adipose tissue. This case of a 76-year-old woman, who presented with possible cardiac tamponade after permanent pacemaker implantation, demonstrates some of the potential pitfalls in the diagnosis of pericardial space abnormalities.

Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation.

OBJECTIVES: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients. BACKGROUND: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown. METHODS: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10). RESULTS: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy). CONCLUSIONS: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.

Identification of viable myocardium by perfusion imaging with intravenous contrast echocardiography after acute myocardial infarction.

Myocardial perfusion contrast echocardiography is evolving into an effective method for the evaluation of myocardial blood flow after acute coronary events. The direct injection of ultrasound contrast agents into the aortic and coronary circulation has been shown to accurately identify areas of viable myocardial tissue. Recently, intravenous ultrasound contrast has been found to be useful in detecting microvascular blood flow after the restoration of blood flow in patients with myocardial infarction. We present the case of a patient in whom intravenous ultrasound contrast assisted in the detection of viable myocardial tissue after an acute ischemic syndrome.

Left ventricular apical diastolic collapse: an unusual echocardiographic marker of postoperative cardiac tamponade.

A 37-year-old woman was evaluated for signs and symptoms of cardiac tamponade 11 days after mitral valve replacement and tricuspid valve repair. The transthoracic echocardiogram showed a large, compartmentalized pericardial effusion that resulted in left ventricular apical diastolic collapse. Also noted were right ventricular posterior wall diastolic collapse and hemodynamic findings consistent with cardiac tamponade. This case highlights the atypical echocardiographic findings in patients with pericardial effusions after cardiac surgery.

Neuropeptide Y and coronary vasoconstriction: role of thromboxane A2.

We previously reported that coronary constriction following neuropeptide Y (NPY) was alleviated by cyclooxygenase blockade. To determine the role of thromboxane A2 (TxA2), anesthetized dogs received two paired doses of NPY given 2 h apart. Nine control dogs received NPY alone. Nine test dogs received one of three TxA2 receptor antagonists given between the doses of NPY. Also, five dogs received NPY during which prostaglandins were measured. In controls, NPY decreased coronary blood flow and increased aortic pressure; coronary resistance was increased significantly. Heart rate fell, and myocardial oxygen consumption was unchanged. Thromboxane receptor blockers significantly relieved the coronary constrictor effect of NPY. The reduction in coronary blood flow was blunted, while heart rate, first derivative of left ventricular pressure, and myocardial oxygen consumption were unchanged. Alleviation by TxA2 receptor blockade paralleled that reported for cyclooxygenase inhibitors. Also, significant increases in coronary venous TxA2 were seen at the time of maximal increases in coronary resistance, while prostacyclin was unchanged. In summary, TxA2 appears to mediate part of the coronary constrictor effect of NPY.