Abstract：
OBJECTIVE:Genetic loci predict <5% of variation in low-density lipoprotein cholesterol (LDL-C) response to statins. Cholestanol and desmosterol are plasma markers of cholesterol absorption and synthesis, respectively. Because statins lower LDL-C by inhibiting cholesterol synthesis, we studied the relationship between cholestanol and desmosterol and LDL-C response to atorvastatin. METHODS:High-risk patients were treated with 80 mg of atorvastatin for 6 weeks. LDL-C response to atorvastatin was related to baseline cholestanol to cholesterol ratio (CCR) and desmosterol. The following comparisons were used: (1) correlates of percentage LDL-C response, (2) baseline characteristics of hyperresponders versus hyporesponders, and (3) binary logistic regression analysis for predictors of achieved LDL-C <70 mg/dL. RESULTS:One hundred fifty-four patients were enrolled of which 118 completed the study with adequate adherence. Average LDL-C reduction was 57% ± 13% (mean ± SD). On univariate analysis, desmosterol and CCR correlated with percentage LDL-C reduction and multivariate modeling explained approximately 16% of the variation in response. Atorvastatin hyperresponders had higher mean desmosterol (P = 0.046) and lower CCR (P = 0.035) than hyporesponders. On logistic regression analysis for the outcome of achieved LDL-C of <70 mg/dL, baseline LDL-C and CCR were significant predictors; odds ratios were 0.932 and 0.979, respectively. CONCLUSIONS:CCR and desmosterol explain more variation in LDL-C response to statin than that reported with pharmacogenomics. CCR and desmosterol may guide lipid-lowering therapy.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Hoenig MR,Walker PJ,Gurnsey C,Beadle K,Johnson Ldoi
10.1097/FJC.0b013e3181f09bcbsubject
Has Abstractpub_date
2010-10-01 00:00:00pages
396-401issue
4eissn
0160-2446issn
1533-4023journal_volume
56pub_type
临床试验,杂志文章abstract：:CGS 26303 has previously been shown to inhibit human endothelin converting enzyme-1 (ECE-1) with an IC50 of 410 nM and to be efficacious in several animal disease models. However, it is a more potent inhibitor of neutral endopeptidase 24.11 (NEP) with an IC50 of 1 nM. The aim of this study was to optimize CGS 26303 fo...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200036051-00014
更新日期：2000-11-01 00:00:00
abstract：:Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although diff...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0000000000000092
更新日期：2014-07-01 00:00:00
abstract：:Toll-like receptors (TLRs) are important in innate immune responses, which are crucial in collateral artery formation (arteriogenesis). TLR4⁻/⁻ mice undergoing hind limb ischemia show decreased perfusion recovery accompanied by an impaired infiltration of inflammatory cells. TLR antagonists are currently developed and...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0000000000000019
更新日期：2014-01-01 00:00:00
abstract：:The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. In addition to its well-established role in maintaining vascular homeostasis, the endothelium has been increasingly recogniz...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0000000000000469
更新日期：2017-06-01 00:00:00
abstract：:This article reviews the relation of cardiac cellular Na+ load and increased force of contraction. Digitalis glycosides and naturally occurring Na+ channel activators are considered. DPI201-106 was described as the first synthetic organic molecule with cardioselective Na+ channel-activating properties and investigated...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-198914003-00006
更新日期：1989-01-01 00:00:00
abstract：:Pinacidil is one of a number of new antihypertensive agents possessing an action that involves an enhanced potassium efflux in cardiac and vascular smooth muscle. An associated feature of pinacidil is a shortening of the cardiac action potential duration, which may constitute a potentially proarrhythmic effect. The pr...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199003000-00016
更新日期：1990-03-01 00:00:00
abstract：:Milrinone, a newly developed analogue of amrinone, possesses potent positive inotropic effects. Electrophysiologic actions of the drug have thus far been reported in only one study conducted on canine Purkinje fibers. The present study used microelectrode techniques to evaluate the electrophysiologic effects of milrin...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198503000-00021
更新日期：1985-03-01 00:00:00
abstract：:Cardiac remodeling is regulated by an extensive intracellular signal transduction network. Each of the many signaling pathways in this network contributes uniquely to the control of cellular adaptation. In the last few years, it has become apparent that multimolecular signaling complexes or "signalosomes" are importan...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0000000000000206
更新日期：2015-03-01 00:00:00
abstract：:The different mechanisms of action of beta-blockers and calcium antagonists could result in an additive therapeutic effect in patients with angina pectoris. Twenty-one male patients aged between 41 and 68 years and suffering from chronic stable angina pectoris and coronary artery disease confirmed by angiography took ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1990-01-01 00:00:00
abstract：:Intracellular [Ca2+]i overloading in cardiomyocytes is a fundamental pathogenic event associated with chronic aldosterone/salt treatment (ALDOST) and accounts for an induction of oxidative stress that leads to necrotic cell death and consequent myocardial scarring. This prooxidant response to Ca2+ overloading in cardi...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181cf0090
更新日期：2010-03-01 00:00:00
abstract：:The electrophysiologic effects of acutely and chronically administered amiodarone on canine Purkinje fibers were assessed using microelectrode techniques to record intracellular action potentials. Chronically treated dogs received amiodarone for 3 weeks (serum levels, 0.91 +/- 0.09 microgram/ml or 1.42 X 10(-6) M). Ac...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:A discussion of important aspects of the effects of prostaglandins on arteries must include (a) the nature of the receptors for the different humoral agents, (b) the potential modulatory role that endogenously produced prostaglandins may play when other vasoactive hormones are present, and (c) the potential for cell-t...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198406002-00016
更新日期：1984-01-01 00:00:00
abstract：BACKGROUND:The sympathetic nervous system (SNS) of the whole body, including cardiac sympathetic nerves, is activated in patients with severe congestive systolic heart failure (CHF). Carvedilol can improve clinical status in such patients. This study aimed to determine how carvedilol acts on the SNS to improve CHF. ME...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/FJC.0b013e31823a94a2
更新日期：2012-02-01 00:00:00
abstract：:The effects of divalent cations on human platelet vasopressin receptor binding characteristics and effects of receptor occupancy on endogenous protein phosphorylation were investigated. Binding of vasopressin to its receptor is modulated by both the nature and the concentration of ions. Whatever the cation present, gu...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198707000-00004
更新日期：1987-07-01 00:00:00
abstract：:The pharmacokinetics and dose proportionality of trandolapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in 12 healthy male volunteers in a four-way randomized crossover study over the therapeutic dose range, 0.5-4 mg. Trandolapril is rapidly absorbed, with a single elimination half-life (...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1994-01-01 00:00:00
abstract：:The amplifier properties associated with the structural changes in the heart and resistance vessels in chronic hypertension together play a major role in maintaining the elevated blood pressure (BP) in chronic hypertension, which is greater than that of the initiating cause. In patients with primary hypertension, long...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199117002-00006
更新日期：1991-01-01 00:00:00
abstract：:The development of tolerance to the antihypertensive effect of clonidine and related imidazolines is clinically recognized. Here, we employed a restricted daytime (8:30 AM until 4:30 PM) clonidine regimen to establish a model of sustained hypotension in spontaneously hypertensive rats (SHRs). Blood pressure (BP), hear...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3180318afb
更新日期：2007-03-01 00:00:00
abstract：:Baroreflex control of renin release following acute and prolonged blood pressure reduction by felodipine administration was investigated in conscious spontaneously hypertensive rats (SHR) fitted with arterial and venous catheters. Basal values of mean arterial pressure (MAP), heart rate (HR), and plasma renin activity...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:We compared platelet function results obtained with the VerifyNow P2Y12 (VN-P2Y12) point-of-care device and the light transmission aggregometry (5 and 20 microM adenosine diphosphate) method using an integrated database of eight clinical trials with a total of 591 subjects. The study was performed in healthy subjects,...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181dd0ec2
更新日期：2010-07-01 00:00:00
abstract：:We studied the influence of dietary L-arginine (L-ARG) supplementation on forearm resistance arteries in vivo and the effect of exogenous addition of L-ARG to subcutaneous arteries isolated from gluteal biopsies. Twenty-six healthy males were recruited, and 16 were randomly allocated in a double-blind protocol to rece...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-199607000-00023
更新日期：1996-07-01 00:00:00
abstract：:We undertook a systematic comparison of the effects of diltiazem and nifedipine and a nonspecific vasodilator, sodium nitroprusside, on renal perfusion, function, and activation of potentially relevant neurohormonal systems in the anesthetized dog. These agents were employed to reduce blood pressure to two levels, a m...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198601000-00006
更新日期：1986-01-01 00:00:00
abstract：:The bronchopulmonary and pressor effects of endothelin-1 (ET-1), a newly described vasoconstrictor peptide produced by endothelial cells, were investigated in the guinea pig. Intravenous injection of ET-1 (1 nmol/kg) induced an increase in pulmonary inflation pressure (PIP) as well as an important and sustained increa...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198900135-00036
更新日期：1989-01-01 00:00:00
abstract：:The human cutaneous microcirculation has so far been studied by rather crude methods, such as plethysmography and 133Xn clearance. New sophisticated and noninvasive techniques are now available, with which the microcirculation of the skin can be continuously studied and measured for hours. With two such methods, i.e.,...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198500073-00007
更新日期：1985-01-01 00:00:00
abstract：:In this retrospective study, a group of 435 patients provided meaningful analyses of blood pressure and dosage data for treatment periods of up to 4.5 years. The protocol, study objectives, and pretreatment demographic characteristics of the group are summarized in this report, which is the first in a series in this i...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：
更新日期：1981-01-01 00:00:00
abstract：AIMS:To determine whether short-term treatment with trimetazidine (TMZ), an antiischemic agent that directly inhibits fatty acid oxidation and results in stimulation of glucose oxidation, may improve myocardial perfusion and left ventricular systolic function in diabetic patients with ischemic cardiomyopathy. METHODS ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1097/FJC.0b013e31817bdd66
更新日期：2008-06-01 00:00:00
abstract：:Experience with angiotensin converting enzyme (ACE) inhibitor drugs as with other antihypertensive agents, is limited in the elderly. Nevertheless, they appear effective and well tolerated but without evidence to suggest that they have any special role in the elderly compared to a younger age group. Most are excreted ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1988-01-01 00:00:00
abstract：:The majority of deaths attributable to hypertension are coronary artery disease (CAD) deaths and, consequently, the prevention of CAD should be the primary aim of hypertension management. Recent meta-analyses confirm the results of the individual hypertension intervention trials, which demonstrated a disappointing sho...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1991-01-01 00:00:00
abstract：:Inhibition of plasma angiotensin II generation does not fully explain the chronic hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. Therefore, the pattern of tissue ACE inhibition in rats was studied after oral administration of perindopril, a new ACE inhibitor. Tissue ACE was measured by quantita...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198812000-00013
更新日期：1988-12-01 00:00:00
abstract：:Cardiovascular disease is a major cause of morbidity and mortality worldwide. Epidemiological studies have clearly demonstrated that chronic psychosocial stress increases the risk of atherosclerotic cardiovascular disease and this may involve multiple mediators and regulating pathways, whereas the precise mechanisms u...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0b013e3182858fac
更新日期：2013-07-01 00:00:00
abstract：:Data of 52 patients, 29 women and 23 men aged 32-68 years (mean age 47 years) with essential hypertension, participating in three open therapeutic trials with either enalapril, lisinopril, or perindopril were evaluated to assess the effects of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid metabol...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/00005344-199401000-00010
更新日期：1994-01-01 00:00:00
