Therapy In Coronary Artery Disease Patients Research Articles

Comparison of Clinical Outcomes After Coronary Artery Bypass Grafting (CABG) With Percutaneous Coronary Intervention (PCI) in Coronary Artery Disease (CAD) Patients With Kidney Disorders: Systematic Review

According to data from the WHO, heart disease continues to be the top cause of mortality worldwide. The 2018 Riskesdas shows that the prevalence of heart disease, including CAD, based on doctors' diagnoses in Indonesia is 1,5%. Management measures in CAD patients are CABG or PCI. The research design used in this study was a literature review using a systematic review method. A systematic literature review comparing CABG and PCI costs is needed to determine optimal therapeutic options in CAD patients. For articles published during the last ten years, a literature search was done using four databases: PubMed, SagePub, Google Scholar, and Science Direct. Based on the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocol (PRISMA-P) 2020 protocol, a literature review was conducted. Eight texts in all met the inclusion and exclusion criteria for the study. Five literatures stating that CABG is better, two other literatures stating that there is no significant post-rehabilitation difference between CABG and PCI, and one literature stating that PCI has better survival after 5 years in CAD patients with impaired renal function. CABG is considered more effective and is recommended as the primary treatment option in CAD patients with a kidney disorder. Nevertheless, PCI can be utilized as an alternate therapy in CAD patients when kidney function and concomitant illnesses are considered.

Association between inflammation, body mass index, and long-term outcomes in patients after percutaneous coronary intervention: A large cohort study.

Association between inflammation, body mass index, and long-term outcomes in patients after percutaneous coronary intervention: A large cohort study.

Effect of high-dose statin therapy on coagulation factors: Lowering of factor XI as a modifier of fibrin clot properties in coronary artery disease

BackgroundMultiple pleiotropic effects of statins include antithrombotic properties with formation of looser fibrin networks more susceptible to lysis. Recently, rosuvastatin 20 mg/d has been reported to decrease coagulation factors (F) VII, FVIII and FXI in venous thrombosis patients. ObjectivesWe investigated how high-dose statin therapy recommended in coronary artery disease (CAD) alters plasma levels of coagulation factors and if such changes might affect fibrin clot properties. MethodsWe studied 130 advanced CAD patients, who initially did not achieve the target low-density lipoprotein cholesterol (LDL-C). Before high-dose statin therapy (rosuvastatin 40 mg/d or atorvastatin 80 mg/d) and 6–12 months after its initiation, FII, FV, FVII, FVIII, FIX, FX, FXI and fibrinogen were assessed. We evaluated the impact of statin-induced alterations to the factors on plasma fibrin clot permeability (Ks) reflecting a fibrin pore size, and clot lysis time (CLT) reflecting fibrinolytic potential. ResultsAt baseline LDL-C (median 3.2, interquartile range 2.7–3.7 mmol/L) was independently associated solely with FXI (β = 0.58, P < 0.001). Median LDL-C reduction by 25% (P < 0.001) on high-dose statin treatment was accompanied by lowering of FVII, FVIII, and FXI (for all P < 0.001). On high-dose statin treatment, Ks (R = 0.65, P < 0.001) inversely associated with CRP (β = −0.41, P < 0.001), LDL-C (β = −0.26, P = 0.001), and FXI (β = −0.18, P = 0.016). In turn, CLT (R = 0.45, P < 0.001) was positively associated with LDL-C (β = 0.19, P = 0.043) and FXI (β = 0.17, P = 0.049). ConclusionsHigh-dose statin therapy in CAD patients decreases FVII, FVIII, and FXI. The statin-induced reduction in FXI may contribute to less prothrombotic fibrin clot phenotype, indicating additional antithrombotic effect of high-dose statins.

Revascularization versus drug therapy for coronary artery disease in patients aged over 80 years: a real-world study.

Revascularization for the treatment of coronary artery disease (CAD) is advancing rapidly and is used increasingly in old patients. This study aimed to compare the efficacy and safety of revascularization with drug therapy in CAD patients aged over 80 years at a real-world clinical setting. A total of 501 CAD patients aged over 80 years were consecutively enrolled from January 2011 to January 2016 in Anzhen Hospital (Beijing, China), Capital Medical University. The patients were treated with percutaneous coronary intervention (PCI) (n=283), coronary artery bypass grafting (CABG) (n=106), or drug therapy (n=112). All-cause mortality, cardiovascular-related mortality, readmission rate, and Seattle Angina Questionnaire (SAQ) score were compared between the three treatment methods. A total of 411 patients (82.04%) were followed with a median duration of 25 months. All-cause mortality and cardiovascular-related mortality in the drug therapy group were significantly higher than the PCI and CABG groups (both P<0.05). Readmission rate for cardiovascular events in the CABG group was significantly lower than the PCI and drug therapy groups (both P<0.05). Scores of physical limitation, angina frequency, treatment satisfaction, and disease perception of the SAQ in the PCI and CABG groups were significantly higher than the drug therapy group (both P<0.05). Scores of angina stability did not differ significant between the three groups (P=0.127). Revascularization is superior to drug therapy in efficacy and safety in the treatment of oldest-old patients with CAD.

Complexity of Antiplatelet Therapy in Coronary Artery Disease Patients.

Patients with coronary artery disease (CAD) presenting with acute coronary syndrome or undergoing coronary stenting are indicated to treatment with dual antiplatelet therapy (DAPT) combining aspirin with a P2Y12 receptor inhibitor. The management of patients with CAD who present with a complex clinical profile due to multiple comorbidities, and/or undergoing complex interventional procedures, remains challenging as a high risk for both ischemic and bleeding events is often present; hence, the risk-benefit balance on the optimal DAPT duration is difficult to evaluate. The complexity of antiplatelet therapy in CAD patients is due to the fact that this complexity embraces several aspects: the coronary anatomy, the number of vascular districts at risk for atherothrombosis, and patient comorbidities, including global frailty. Recent randomized and epidemiological studies have highlighted subgroups that could benefit from prolonged antithrombotic treatment, as well as frail patients, who may be better suited to a shorter course of therapy. We provide an overview of the current knowledge regarding treatment with DAPT, along with suggestions on its management.

MiR-548aq-3p is a novel target of Far infrared radiation which predicts coronary artery disease endothelial colony forming cell responsiveness

Non-invasive far infrared radiation (FIR) has been observed to improve the health of patients with coronary artery disease (CAD). Endothelial colony forming cells (ECFCs) contribute to vascular repair and CAD. The goal of this study was to uncover the role of FIR in ECFCs function and to reveal potential biomarkers for indication of FIR therapy in CAD patients. FIR significantly enhanced in vitro migration (transwell assay) and tube formation (tube length) capacities in a subpopulation of CAD ECFCs. Clinical parameters associated with the responsiveness of ECFCs to FIR include smoking and gender. ECFCs from CAD patients that smoke did not respond to FIR in most cases. In contrast, ECFCs from females showed a higher responsiveness to FIR than ECFCs from males. To decipher the molecular mechanisms by which FIR modulates ECFCs functions, regardless of sex, RNA sequencing analysis was performed in both genders of FIR-responsive and FIR-non/unresponsive ECFCs. Gene Ontology (GO) analysis of FIR up-regulated genes indicated that the pathways enriched in FIR-responsive ECFCs were involved in cell viability, angiogenesis and transcription. Small RNA sequencing illustrated 18 and 14 miRNAs that are up- and down-regulated, respectively, in FIR-responsive CAD ECFCs in both genders. Among the top 5 up- and down-regulated miRNAs, down-regulation of miR-548aq-3p in CAD ECFCs after FIR treatment was observed in FIR-responsive CAD ECFCs by RT-qPCR. Down-regulation of miR-548aq-3p was correlated with the tube formation activity of CAD ECFCs enhanced by FIR. After establishment of the down-regulation of miR-548aq-3p by FIR in CAD ECFCs, we demonstrated through overexpression and knockdown experiments that miR-548aq-3p contributes to the inhibition of the tube formation of ECFCs. This study suggests the down-regulation of miR-548aq-3p by FIR may contribute to the improvement of ECFCs function, and represents a novel biomarker for therapeutic usage of FIR in CAD patients.

Add-on ezetimibe treatment to low-dose statins vs medium-intensity statin monotherapy in coronary artery disease patients with poorly controlled dyslipidemia.

Although ezetimibe has potential value as an add-on therapy to statins, it is not established whether the addition of ezetimibe to statin therapy is more effective than double-dose statin monotherapy. We conducted a crossover design study. Twenty-one coronary artery disease (CAD) patients whose lipid profiles had not achieved Japanese guideline recommendations (JAS 2017), despite receiving low-dose statin therapy, were divided into two groups. Group A received ezetimibe 10 mg in addition to the baseline dose of statin for the first 3 months and was then switched to monotherapy with a double dose of statin for the next 3 months. Group B first received a double dose of statin for 3 months and was then switched to ezetimibe 10 mg in addition to a baseline dose of statin for the next 3 months. Compared with the baseline, double-dose statin therapy reduced low-density lipoprotein (LDL)-cholesterol (from 118 ± 22 to 104 ± 15 mg/dL, P < 0.05) and malondialdehyde-modified LDL (MDA-LDL) (from 142 ± 35 to 126 ± 24 U/L, P < 0.05) but did not lower high-sensitivity C-reactive protein (hsCRP) (3.02 ± 0.47 and 2.98 ± 0.41 log [ng/ml]). The addition of ezetimibe to a baseline dose of statin further reduced LDL-cholesterol (to 89 ± 15, P < 0.0001) and MDA-LDL (to 114 ± 22 U/L, P < 0.001) and reduced hsCRP (to 2.78 ± 0.38 log (ng/ml), P < 0.05). The changes in the levels of MDA-LDL (R = 0.548, P = 0.010) and hsCRP (R = 0.473, P < 0.05) were significantly correlated with the change in the LDL-cholesterol level after the addition of ezetimibe. Add-on ezetimibe treatment appears superior to double-dose statin therapy in CAD patients with poorly controlled dyslipidemia in terms of reductions in LDL-cholesterol level, lipid peroxidation, and inflammation.

Extracorporeal Shock Wave Therapy for Coronary Artery Disease: Relationship of Symptom Amelioration and Ischemia Improvement.

Objective(s):The current management of coronary artery disease (CAD) relies on three major therapeutic options, namely medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). However, severe CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW) therapy reported on human for the first time. This treatment resulted in better myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy, angina symptoms, and exercise tolerance. The aim of the present study was to investigate: myocardial perfusion images and evaluate the relationship between the ischemia improvement and symptom amelioration by SW therapy.Methods:We treated ten patients (i.e., nine males and one female) with cardiac SW therapy who had CAD but not indicated for PCI or CABG and aged 63–89 years old. After the SW therapy, all patients were followed up for three months to evaluate any amelioration of the myocardial ischemia based on symptoms, adenosine stress thallium scintigraphy, transthoracic echocardiography, and blood biochemical examinations.Results:The changes in various parameters were evaluated before and after cardiac SW therapy. The cardiac SW therapy resulted in a significant improvement in the symptoms as evaluated by the Canadian Cardiovascular Society [CCS] class score (P=0.016) and a tendency to improve in summed stress score (SSS) (P=0.068). However, no significant improvement was observed in the summed rest score (SRS), summed difference score (SDS), left ventricular wall motion score index (LVWMSI), N-terminal pro-brain natriuretic, and troponin I. The difference of CCS class score (ΔCCS) was significantly correlated with those of SSS (ΔSSS) and SDS (ΔSDS) (r=0.69, P=0.028 and r=0.70, P=0.025, respectively). There was no significant correlation between ΔCCS and other parameters. Furthermore, no significant difference was observed between the CCS improved and non-improved groups in terms of the baseline characteristics.Conclusion:The current study demonstrated the potential efficacy and safety of Cardiac SW therapy in CAD patients. As the findings indicated, symptom amelioration was associated with ischemia improvement by extracorporeal shock wave therapy for the CAD patients.

Does Enhanced External Counterpulsation (EECP) Significantly Affect Myocardial Perfusion?: A Systematic Review & Meta-Analysis.

BackgroundEnhanced external counterpulsation (EECP) is currently applied for treating coronary artery disease (CAD) patients. However, the mechanism(s) by which EECP ameliorates angina pectoris and long-term left ventricular function remain largely unknown. The aim of this study will be to assess whether EECP significantly affects myocardial perfusion in CAD patients through a systematic review and meta-analysis of the available literature.MethodsMEDLINE, EMBASE, and Cochrane CENTRAL databases were searched for prospective studies on CAD patients that underwent EECP and reported myocardial perfusion data pre- and post-EECP. The impact of EECP was assessed based on the weighted mean difference (WMD) in myocardial perfusion from pre-EECP to post-EECP. Statistical heterogeneity was assessed by the I2 index. Publication bias was assessed through visual inspection of the funnel plot as well as Begg’s and Egger’s testing.ResultsStandard EECP therapy (i.e., 35–36 one-hour sessions within a seven-week period) significantly increased myocardial perfusion in CAD patients (pooled WMD: -0.19, 95% CI: -0.38 to 0.00, p = 0.049). A random effects analysis was applied on account of significant heterogeneity (I2 = 89.1%, p = 0.000). There was no evidence of significant publication bias (Begg’s p = 0.091; Egger’s p = 0.282).ConclusionsStandard EECP therapy significantly increases myocardial perfusion in CAD patients. This study’s findings support the continued use of standard EECP therapy in CAD patients and provides one putative physiological mechanism to help explain the improvements in angina pectoris and long-term left ventricular function observed in CAD patients after EECP therapy.

Assessment of platelet‐derived thrombogenicity with the total thrombus‐formation analysis system in coronary artery disease patients receiving antiplatelet therapy

Accurate evaluation of thrombogenicity helps to prevent thrombosis and excessive bleeding. The total thrombus-formation analysis system (T-TAS) was developed for quantitative analysis of platelet thrombus formation by the use of microchips with thrombogenic surfaces (collagen, platelet chip [PL-chip]; collagen plus tissue factor, atherome chip [AR-chip]). We examined the utility of the T-TAS in the assessment of the efficacy of antiplatelet therapy in patients with coronary artery disease (CAD). In this cross-sectional study, 372 consecutive patients admitted to the cardiovascular department were divided into three groups: patients not receiving any antiplatelet therapy (control, n = 56), patients receiving aspirin only (n = 69), and patients receiving aspirin and clopidogrel (n = 149). Blood samples were used for the T-TAS to measure the platelet thrombus-formation area under the curve (AUC) at various shear rates (1500 s(-1) [PL18 -AUC10 ] and 2000 s(-1) [PL24 -AUC10 ] for the PL-chip; 300 s(-1) [AR10 -AUC30 ] for the AR-chip). The on-clopidogrel platelet aggregation was measured by the use of P2Y12 reaction units (PRUs) with the VerifyNow system. The mean PL24 -AUC10 levels were 358 ± 111 (± standard deviation) (95% confidence interval [CI] 328.9-387.1) in the control group, 256 ± 108 (95% CI 230.5-281.5) in the aspirin group, and 113 ± 91 (95% CI 98.4-127.6) in the aspirin/clopidogrel group. In the aspirin/clopidogrel group, the PL24 -AUC10 was higher in poor metabolizers (PMs) with cytochrome P450 2C19(CYP2C19) polymorphisms (152 ± 112, 95% CI 103.4-200.6) than in the non-PM group (87 ± 74, 95% CI 73.8-100.2). Our findings suggest that the PL24 -AUC10 level measured by the T-TAS is a potentially suitable index for the assessment of antiplatelet therapy in CAD patients.

Statin use, intensity, and 3-year clinical outcomes among older patients with coronary artery disease

Clinical trial evidence suggests that statin therapy reduces adverse clinical events and provides even greater benefit at high-intensity doses in coronary artery disease (CAD) patients, yet few studies have examined this in clinical practice. We linked detailed in-hospital data (2005-2009) on 15,729 Get With The Guidelines-CAD patients ≥65 years prescribed statins to Centers for Medicare and Medicaid Services claims. High-intensity statin therapy was defined as discharge prescription of atorvastatin ≥40 mg, rosuvastatin ≥20 mg, or simvastatin 80 mg. We used Kaplan-Meier curves to calculate all-cause mortality, major adverse cardiovascular events (MACEs), and all-cause readmission at 3 years postdischarge; log-rank tests to compare survival via overall statin use and intensity; and Cox proportional hazards regression with inverse propensity weighting to evaluate adjusted rates of adverse events over 3 years postdischarge. Of 35,903 patients meeting inclusion criteria, 24,367 (67.9%) were discharged on statin. Of 15,729 patients with statin intensity information, 4488 (28.5%) received high-intensity therapy; these recipients were more often younger, male, and had acute myocardial infarction. After inverse propensity weighting adjustment, statin use was associated with significantly lower hazards of mortality (hazard ratio 0.89, 95% CI 0.84-0.93) and MACE (0.92, 0.88-0.96), but not readmission (1.01, 0.97-1.04). High-intensity (vs low/moderate) use was not associated with lower risk of all-cause mortality (1.07, 1.00-1.14), MACE (1.05, 0.99-1.11), or readmission (1.05, 1.00-1.10). Clinically relevant subgroups had similar results. In older hospitalized CAD patients, use of statin therapy at discharge was associated with improved long-term outcomes. Consistent with current American College of Cardiology/American Heart Association cholesterol guideline recommendations supporting moderate- rather than high-intensity statin therapy in CAD patients >75 years, high-intensity statin therapy was not associated with incremental benefit in this older population.

Abstract P014: Poor Blood Pressure Control and Severe Coronary Artery Lesions Are Risks of Cerebral Microbleeds in Patients With Coronary Artery Disease During Antiplatelet Therapy

Background and Purpose: Brain hemorrhage is a serious complication of antiplatelet therapy, particularly dual antiplatelet therapy (DAPT), in patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention (PCI). Cerebral microbleeds (CMBs) detected on MRI is a surrogate of symptomatic brain hemorrhage. However, little is known regarding CMBs in CAD patients during long-term antiplatelet therapy. Therefore, we investigated the temporal change of CMBs during antiplatelet therapy in CAD patients after PCI. Method: Brain MRI was performed at baseline and after 8-month follow-up in consecutive 14 patients who underwent PCI and antiplatelet therapy (DAPT in 13 patients). Results: Baseline MRI revealed CMBs in 2 patients (14%). New CMBs were detected by follow-up MRI in 2 other patients (14%). Although blood pressure (BP) at baseline did not differ between the CMB-positive and CMB-negative patients, BP after 8 months was significantly higher in CMB-positive patients than CMB-negative ones (systolic BP: p=0.03, diastolic BP: p=0.02). Moreover, CMB-positive patients had greater number of coronary artery lesions and higher SYNTAX score at baseline than CMB-negative patients (Figure). Conclusions: CAD patients with poor BP control and severe coronary artery lesions would be at higher risk for CMBs and eventually brain hemorrhage during antiplatelet therapy. Accordingly, strict coronary risk control, especially BP control, is necessary in CAD patients receiving long-term antiplatelet therapy.

Quality of medical management in coronary artery disease.

BACKGROUND AND OBJECTIVESPatients with coronary artery disease (CAD) are at high risk of recurrent adverse cardiac events. Such risk can be diminished through a guideline-recommend optimal medical therapy (OMT), defined as adherence to appropriate antiplatelet therapy, lipid-lowering agents, beta-blockers and angiotensin-converting enzyme inhibitors, blood pressure <140/90 mm Hg (<130/80 mm Hg in diabetics and renal disease patients), low-density lipoprotein (LDL) <2 mmol/L, smoking cessation and aerobic physical activity, and hemoglobin (Hb) A1c <7%. Unfortunately, preliminary data suggest a wide gap between recommended and actual practices. The study aims to estimate the rate of achieving of OMT in CAD patients in Qassim Province.DESIGN AND SETTINGSThis observational study enrolled 207 consecutive CAD patients seen in cardiology clinic in Prince Sultan Cardiac Center in Qassim between January 2012 and May 2012.METHODSEligible participants were over the age of 18, with CAD documented by either noninvasive testing or by coronary angiogram. We collected the demographic, medications, laboratory, and clinical data through in-person interviews, medical records, and an electronic patient database.RESULTSOMT was achieved in only 10.4% of CAD patients. The rate of achievement of target systolic blood pressure was 76.5%, target diastolic blood pressure 88%, target LDL 68%, adherence to medications 91%. Diabetes was common (64% of all patients), and only 24% of these patients achieved the target HbA1c.CONCLUSIONThe poor achievement of optimal medical therapy in CAD patients contributes to preventable mortality, morbidity, and health care costs. The observed shortcomings warrant investment in strategies to achieve OMT in these high-risk patients.

Clopidogrel non-responsiveness and risk of cardiovascular morbidity

We performed this meta-analysis to update the clinical evidences on the relation between clopidogrel non-responsiveness and clinical outcomes in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. An electronic literature search through MEDLINE, EMBASE, Web of Science, and the Cochrane Library and bibliographies of retrieved articles up to January, 2009 was conducted. Studies were included if they had a cohort prospective design, if they analysed clopidogrel responsiveness in CAD patients in relation to death and/or occurrence of adverse coronary events during follow-up, and if they reported an adequate statistical analysis. Fourteen studies, totalling 4,564 CAD patients followed for a time ranging from 14 days to one year, were included. The cumulative analysis reported that residual platelet reactivity despite clopidogrel treatment was significantly associated with an increased risk of death and/or thrombotic recurrences (odds ratio [OR] 5.67, 95% confidence interval [CI] 2.97 to 10.84; p<0.00001). However, four studies contributed to a consistent heterogeneity of the model and evidenced a significant risk of publication bias, so were excluded from the analysis. This exclusion, however, did not influence the overall result, by confirming the increased risk of cardiovascular recurrences for patients with a poor response to clopidogrel treatment (OR 3.58, 95%CI 2.54 to 5.05; p<0.00001). The present updated meta-analysis documents a significant association between residual platelet reactivity under clopidogrel treatment and recurrent cardiovascular events, so suggesting the relevance of ongoing interventional studies aimed at tailoring the antithrombotic therapy in CAD patients.

The Rationale and Design of the Perindopril Genetic Association Study (PERGENE): A Pharmacogenetic Analysis of Angiotensin-Converting Enzyme Inhibitor Therapy in Patients with Stable Coronary Artery Disease

Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40 degrees C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease.

Sex-Based Differences in Vascular Repair With Bone Marrow Cell Therapy: Relevance of Regulatory and Th2-type Cytokines

Objectives There are differences in symptoms, risk stratification, and efficacy of pharmacological treatments between men and women with coronary artery disease (CAD). The results of clinical studies of cell therapy in CAD patients are mixed. The relevance of sex to response to cell therapy is unknown. We investigated sex-based differences in response to bone marrow mononuclear cells (BM-MNCs) in atherosclerotic apoliproprotein E-knockout (ApoE −/−) mice. Methods Twenty-three male and 27 female ApoE −/− mice fed on a high-fat diet received four intravenous BM-MNC injections (C57BL6/J mice) starting at 14 weeks of age; male or female BM-MNCs were administered. Thirteen male and 20 female atherosclerotic ApoE −/− mice received vehicle. Aortic plaque burden (%), recipient bone marrow progenitor cell profiles (FACS-LSR II, FlowJo) and 22 circulating cytokine panel (LINCOplex) were quantified and analyzed statistically (SSPS, P ≤ .05). Results Quantitative and semiquantitative results are presented. Increased G-CSF levels correlated with plaque reduction ( r = −.86, P = .0004). G-CSF was clustered with IL-15. Conclusions Female but not male BM-MNCs exhibited atheroprotection in male atherosclerotic ApoE −/− mice. Plaque lesions did not attenuate atherosclerosis in female ApoE −/− mice with BM-MNCs of either donor sex. An increase in regulatory and in Th2-type response may be required for atheroprotection. Sex-based differences in vascular repair have implications for cell therapy trials in CAD.

Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function?

Early clinical studies investigating the role of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure unexpectedly demonstrated a possible reduction in coronary heart disease endpoints. Two large scale clinical trials, HOPE and EUROPA, both studies in patients with coronary artery disease (CAD) but without clinical evidence of heart failure, showed a highly significant improvement in coronary heart disease outcomes on treatment with ramipril and perindopril, respectively, in contrast, in a similar population, PEACE was unable to demonstrate such benefit with trandolapril. Meta-analyses of all trials involving ACE-inhibitors showed a highly significant improvement in coronary heart disease endpoints. Current ESC guidelines recommend ACE-inhibitor therapy in CAD patients with co-existing indications for ACE-inhibitors, such as hypertension, heart failure, left ventricular dysfunction, prior MI was left ventricular dysfunction, or diabetes (class I, level of evidence A). These guidelines also recommend ACE-inhibitor therapy in all patients with angina and proven coronary disease (class IIa, level of evidence B). However, in angina patients without independent indication for ACE-inhibitor treatment, the anticipated benefit should be weighted against the costs and risks of side effects; in these patients, only agents and doses of proven efficacy for secondary prevention should be employed.