Journal of Cardiovascular Pharmacology and Therapeutics最新文献

{"title":"Bioassays of Humoral Cardioprotective Factors Released by Remote Ischemic Conditioning in Patients Undergoing Coronary Artery Bypass Surgery","authors":"H. Lieder, Pia Tüller, Felix Braczko, A. Zandi, M. Kamler, M. Thielmann, G. Heusch, P. Kleinbongard","doi":"10.1177/10742484221097273","DOIUrl":"https://doi.org/10.1177/10742484221097273","url":null,"abstract":"Remote ischemic conditioning (RIC) induces the release of circulating cardioprotective factors and attenuates myocardial ischemia/reperfusion injury. Evidence for such humoral cardioprotective factor(s) is derived from transfer with plasma (derivatives) from one individual undergoing RIC to another individual’s heart, even across species. With transfer into an isolated perfused heart, only a single plasma (derivative) sample can be studied with infarct size as endpoint, and therefore the comparison of samples before and after RIC or between RIC and placebo is hampered by the inter-individual variation of infarct sizes in isolated perfused hearts. We therefore developed a preparation of cardiomyocytes from a single mouse heart, where aliquots of the same heart can undergo hypoxia/reoxygenation (H/R) with exposure to buffer, RIC, or placebo samples without or with pharmacological blockade. To validate this approach, we used plasma dialysates taken before and after RIC from patients undergoing coronary bypass grafting who had experienced protection by RIC (troponin release ↓ by 28% vs placebo). The cardiomyocyte bioassay had little variation after H/R with buffer (mean ± standard deviation; 7% ± 2% viable cells) and demonstrated preserved viability after RIC (15% ± 5% vs 6% ± 3% before). For comparison, infarct size in isolated mouse hearts after global ischemia and reperfusion was 22% ± 14% of left ventricular mass after versus 42% ± 14% before RIC. Stattic, an inhibitor of signal transducer and activator of transcription (STAT)3 protein, abrogated protection in the cardiomyocytes. We have thus established a cardiomyocyte bioassay to analyze RIC’s protection which minimizes inter-individual variation and the use of animals.","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48066244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renin-Angiotensin-Aldosterone System Inhibitors, Statins, and Beta-Blockers in Diabetic Patients With Critical Limb Ischemia and Foot Lesions","authors":"P. Cimaglia, D. Bernucci, L. Cardelli, A. Carone, G. Scavone, M. Manfrini, S. Censi, S. Calvi, R. Ferrari, G. Campo, L. Dalla Paola","doi":"10.1177/10742484221101980","DOIUrl":"https://doi.org/10.1177/10742484221101980","url":null,"abstract":"Medical therapy for secondary prevention is known to be under-used in patients with peripheral artery disease (PAD). Few data are available on the subgroup with critical limb ischemia (CLI). Prescription of cardiovascular preventive therapies was recorded at discharge in a large, prospective cohort of patients admitted for treatment of CLI and foot lesions, stratified for coronary artery disease (CAD) diagnosis. All patients were followed up for at least 1 year. The primary endpoint was major adverse cardiovascular events (MACE). 618 patients were observed for a median follow-up of 981 days. Renin-angiotensin-aldosterone system (RAAS) inhibitors, statins, beta-blockers, and antithrombotic drugs were prescribed in 52%, 80%, 51%, and 99% of patients, respectively. However, only 43% of patients received optimal medical therapy (OMT), defined as the combination of RAAS inhibitor plus statin plus at least one antithrombotic drug. It was observed that the prescription of OMT was not affected by the presence of a CAD diagnosis. On the other hand, it was noticed that the renal function affected the prescription of OMT. OMT was independently associated with MACE (HR 0.688, 95%CI 0.475-0.995, P = .047) and, after propensity matching, also with all-cause mortality (HR 0.626, 95%CI 0.409-0.958, P = .031). Beta-blockers prescription was not associated with any outcome. In conclusion, patients with critical limb ischemia are under-treated with cardiovascular preventive therapies, irrespective of a CAD diagnosis. This has consequences on their prognosis.","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46761896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric Oxide Is the Cause of Nitroglycerin Tolerance: Providing an Old Dog New Tricks for Acute Heart Failure","authors":"W. Kaesemeyer, T. Suvorava","doi":"10.1177/10742484221086091","DOIUrl":"https://doi.org/10.1177/10742484221086091","url":null,"abstract":"Our paper highlights the past 50 years of research focusing solely on tolerance involving nitroglycerin (glyceryl trinitrate, GTN). It also identifies and discusses inconsistencies in previous mechanistic explanations that have failed to provide a way to administer GTN continuously, free of limitations from tolerance and without the requirement of a nitrate-free interval. We illustrate, for the first time in 135 years, a mechanism whereby nitric oxide, the mediator of vasodilation by GTN, may also be the cause of tolerance. Based on targeting superoxide from mitochondrial complex I, uncoupled by glutathione depletion in response to nitric oxide from GTN, a novel unit dose GTN formulation in glutathione for use as a continuous i.v. infusion has been proposed. We hypothesize that this will reduce or eliminate tolerance seen currently with i.v. GTN. Finally, to evaluate the new formulation we suggest future studies of this new formulation for the treatment of acute decompensated heart failure.","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45114431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duration of Heart Failure With Reduced Ejection Fraction Associated With Electrocardiographic Outcomes Before and After Sacubitril/Valsartan","authors":"Po-Lin Lin, Ying-Hsiang Lee, Lawrence Yu-Min Liu, C. Tsai, Ten-Fang Yang, Wei-Ru Chiou, Mu-Yang Hsieh, Hung-Yu Chang, Chun-Che Huang","doi":"10.1177/10742484221107799","DOIUrl":"https://doi.org/10.1177/10742484221107799","url":null,"abstract":"Aim: Changes in QRS duration in patients with heart failure with reduced ejection fraction (HFrEF) after sacubitril/valsartan therapy is not fully understood. This study aimed to assess the association of duration of HFrEF diagnosis with electrocardiographic and echocardiographic outcomes between before and after sacubitril/valsartan. Methods: We included HFrEF patients who received naïve sacubitril/valsartan therapy for ≥3 months, between January 2016 and March 2018. All patients were divided into 2 groups based on their duration of HFrEF. Generalized linear models were analyzed the cardiac outcomes after sacubitril/valsartan therapy by HFrEF duration. Results: Among these, 42 patients were HFrEF duration of <1 year and 47 patients were ≥1 year. The mean difference of QRS duration was lesser in the <1-year group than in the ≥1-year group (−2.3 msec vs 6.3 msec; P = .029). However, the mean difference of left ventricular ejection fraction (LVEF) was higher in the ≥1-year group (13.8% vs 5.8%; P = .008). After adjusting for patient demographics and clinical characteristics, the ≥1-year group had a significantly prolonged QRS duration (coefficient = 11; 95% confidence interval [CI], 0.3-21.7) and an unfavorable LVEF recovery (coefficient = −10.3; 95% CI −14.5 to −6.1) compared with the <1-year group. Conclusion: Prolonged QRS durations and unfavorable LVEF recoveries after sacubitril/valsartan therapy were observed in patients with HFrEF duration of ≥1 year. Earlier diagnosis of HFrEF and appropriate medication treatment may be beneficial in the improvement of QRS duration and LVEF recovery.","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48067283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Valproic Acid Use With Post-Myocardial Infarction Heart Failure Development: A Meta-Analysis of Two Retrospective Case-Control Studies.","authors":"Joseph D English, Shuo Tian, Zhong Wang, Jasmine A Luzum","doi":"10.1177/10742484221140303","DOIUrl":"10.1177/10742484221140303","url":null,"abstract":"<p><strong>Background: </strong>Despite advances in treatments, myocardial infarction (MI) remains a significant cause of morbidity and mortality worldwide. Our team has previously shown that valproic acid (VPA) is cardio-protective when administered to rats post-MI. The aim of this study was to investigate the association of VPA use with post-MI heart failure (HF) development in humans.</p><p><strong>Methods: </strong>This study was a random effects meta-analysis of two retrospective case-control studies collected from electronic health record (Michigan Medicine) and claims data (OptumInsight). Cases with an active prescription for VPA at the time of their MI were matched 1:4 to controls not taking VPA at the time of their MI by multiple demographic and clinical characteristics. The primary outcome, time-to-HF development, was analyzed using the Fine-Gray competing risks model of any VPA prescription versus no VPA prescription. An exploratory analysis was conducted to evaluate the association of different VPA doses (≥1000 mg/day vs <1000 mg/day vs 0 mg/day VPA).</p><p><strong>Results: </strong>In total, the datasets included 1313 patients (249 cases and 1064 controls). In the meta-analysis, any dose of VPA during an MI tended to be protective against incident HF post-MI (HR = 0.87; 95% CI = 0.72-1.01). However, when stratified by dose, high-dose VPA (≥1000 mg/day) significantly associated with 30% reduction in risk for HF post-MI (HR = 0.70; 95% CI = 0.49-0.91), whereas low-dose VPA (<1000 mg/day) did not (HR = 0.95; 95% CI = 0.78-1.13).</p><p><strong>Conclusion: </strong>VPA doses ≥1000 mg/day may provide post-MI cardio-protection resulting in a reduced incidence of HF.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221140303"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/98/nihms-1861271.PMC9841513.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiplatelet Therapy and Bleeding Outcomes With CYP2C19 Genotyping.","authors":"James C Coons,&nbsp;James M Stevenson,&nbsp;Ami Patel,&nbsp;A J Conrad Smith,&nbsp;Linda Prebehalla,&nbsp;Philip E Empey","doi":"10.1177/10742484221143246","DOIUrl":"https://doi.org/10.1177/10742484221143246","url":null,"abstract":"<p><strong>Purpose: </strong>The impact of antiplatelet therapy with availability of CYP2C19 genotyping on bleeding in a real-world setting has not been extensively studied.</p><p><strong>Methods: </strong>Prospective, single-center, cohort study conducted between December 2015 and October 2019 with 1-year follow-up. Patients underwent percutaneous coronary intervention (PCI), CYP2C19 genotyping, and received P2Y12 inhibitor therapy. The primary outcome was time to first bleed of any severity using Bleeding Academic Research Consortium criteria. Secondary outcomes included time to first major bleed and rates of antiplatelet switching.</p><p><strong>Results: </strong>The primary outcome occurred in 697 of 2091 (33%) participants at a median of 15 days. Major bleeding occurred in 176 (8%) of patients. Compared to clopidogrel, treatment with ticagrelor or prasugrel was associated with increased risk of any bleeding (adjusted HR [aHR] 2.04, 95% CI 1.69-2.46). For patients without CYP2C19 no function alleles, treatment with prasugrel or ticagrelor was associated with increased risk of any bleeding (aHR 2.31, 95% CI 1.83-2.90). Similar associations were observed for major bleeding. No difference in ischemic events was observed. Among patients discharged on ticagrelor or prasugrel, 199 (36%) were de-escalated to clopidogrel within 1 year. De-escalation was more likely after a bleed if patients did not have a no function allele (35.9% vs 19.1%; <i>P</i> = .02).</p><p><strong>Conclusion: </strong>Bleeding is common in post-PCI patients on antiplatelet therapy. Patients on high potency agents had higher bleeding risk in the population at-large and in non-carriers of CYP2C19 no function alleles. Genotype-guided antiplatelet de-escalation should be further explored in prospective studies.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221143246"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10354586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 3 Randomized Controlled Trial to Evaluate Efficacy and Safety of New-Formulation Zenon (Rosuvastatin/Ezetimibe Fixed-Dose Combination) in Primary Hypercholesterolemia Inadequately Controlled by Statins.","authors":"Alberico L Catapano,&nbsp;Michal Vrablik,&nbsp;Yuri Karpov,&nbsp;Baptiste Berthou,&nbsp;Megan Loy,&nbsp;Marie Baccara-Dinet","doi":"10.1177/10742484221138284","DOIUrl":"https://doi.org/10.1177/10742484221138284","url":null,"abstract":"<p><strong>Objective: </strong>In primary hypercholesterolemia many people treated with statins do not reach their plasma LDL-C goals and are at increased risk of cardiovascular disease (CVD). This study aimed to evaluate efficacy and safety of a new fixed-dose combination (FDC) formulation of rosuvastatin/ezetimibe (R/E) in this population.</p><p><strong>Methods: </strong>This was a multicenter, multinational, randomized, double-blind, double-dummy, active-controlled, parallel-arm study of FDC R/E in people with primary hypercholesterolemia at very high risk (VHR) or high risk (HR) of CVD, inadequately controlled with 20 mg or 10 mg stable daily dose of rosuvastatin or equipotent dose of another statin. The primary objective was to demonstrate superiority of FDC R/E versus rosuvastatin monotherapy uptitrated to 40 mg (R40) or 20 mg (R20) in reduction of LDL-C after 6 weeks.</p><p><strong>Results: </strong>Randomized VHR participants (n = 244) were treated with R40, R40/E10, or R20/E10; randomized HR participants (n = 208) received R10/E10 or R20. In VHR participants, superiority of R40/E10 and R20/E10 versus R40 was demonstrated on LDL-C percent change from baseline to Week 6 with least squares mean differences (LSMD) of -19.66% (95% CI: -29.48% to -9.84%; <i>P</i> < .001) and -12.28% (95% CI: -22.12% to -2.44%; <i>P</i> = .015), respectively. In HR participants, superiority of R10/E10 over R20 was not demonstrated (LSMD -5.20%; 95% CI: -15.18% to 4.78%; <i>P</i> = .306), despite clinically relevant LDL-C reduction with R10/E10. No unexpected safety findings were reported.</p><p><strong>Conclusions: </strong>The results from this study suggest that R/E FDCs improve LDL-C reduction and goal achievement in people with primary hypercholesterolemia inadequately controlled with statins and at VHR/HR of CVD.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221138284"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10466359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis.","authors":"Jorge L Reyes,&nbsp;Charles A Herzog,&nbsp;Heng Yan,&nbsp;Nicholas S Roetker,&nbsp;James B Wetmore","doi":"10.1177/10742484221142220","DOIUrl":"https://doi.org/10.1177/10742484221142220","url":null,"abstract":"<p><strong>Background: </strong>The association of patient and prescriber characteristics with use of warfarin versus direct-acting oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is not well studied.</p><p><strong>Methods: </strong>The 20% Centers for Medicare & Medicaid Services Parts A, B, and D claims data from 2010 to 2017 were used to identify patients with stage 3, 4, or 5 CKD and AF who received a DOAC (apixaban, dabigatran, rivaroxaban) or warfarin. Prescribers were categorized as cardiologists, primary care providers (PCPs), and others. Using logistic regression, we estimated odds ratios (ORs) for the association of baseline characteristics and prescriber specialty with first use of a DOAC, relative to warfarin.</p><p><strong>Results: </strong>We identified 22,739 individuals with CKD who were newly initiated on oral anticoagulation for AF. New DOAC prescriptions increased from 490 in 2011 to 3261 in 2017, and displaced warfarin over time (1849, 2011; 945, 2017). By Q4 of 2014, cardiologists prescribed DOACs as initial treatment more frequently than warfarin, but non-cardiologists did not do so until 2015. As of 2017, apixaban was the most widely prescribed anticoagulant, comprising 56% and 50% of prescriptions by cardiologists and non-cardiologists, respectively. PCPs (OR 0.54, 0.51-0.58) and other providers (OR 0.55, 0.51-0.59) were less likely than cardiologists to prescribe DOACs.</p><p><strong>Conclusions: </strong>DOAC prescriptions, particularly apixaban, increased over time and gradually displaced warfarin. The total number of patients with AF and CKD receiving anticoagulation increased over time. Cardiologists increased DOAC prescriptions more rapidly than non-cardiologists.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221142220"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10479707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling.","authors":"Sergey V Popov,&nbsp;Ekaterina S Prokudina,&nbsp;Alexander V Mukhomedzyanov,&nbsp;Natalia V Naryzhnaya,&nbsp;Huijie Ma,&nbsp;Jitka M Zurmanova,&nbsp;Peter F M van der Ven,&nbsp;Leonid N Maslov","doi":"10.1177/1074248420985301","DOIUrl":"https://doi.org/10.1177/1074248420985301","url":null,"abstract":"<p><p>Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"575-584"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1074248420985301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39286851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?","authors":"Ruihai Zhou,&nbsp;George A Stouffer,&nbsp;Sidney C Smith","doi":"10.1177/10742484211023632","DOIUrl":"https://doi.org/10.1177/10742484211023632","url":null,"abstract":"<p><p>Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as \"bad\" cholesterol and high-density lipoprotein cholesterol (HDL-C) as \"good\" cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"533-549"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/10742484211023632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39246501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}