Nonfatal Cerebrovascular Events Research Articles

Opium consumption and long-term outcomes of CABG surgery in patients without modifiable risk factors.

The question about the significance of opium consumption as a coronary artery disease (CAD) risk factor still remains open. The present study aimed to evaluate the association between opium consumption and long term outcomes of coronary artery bypass grafting (CABG) in patients without standard modifiable CAD risk factors (SMuRFs; hypertension, diabetes, dyslipidemia, and smoking). In this registry-based design, we included 23,688 patients with CAD who underwent isolated CABG between January 2006 to December 2016. Outcomes were compared in two groups; with and without SMuRF. The main outcomes were all-cause mortality, fatal and nonfatal cerebrovascular events (MACCE). Inverse probability weighting (IPW) adjusted Cox's proportional hazards (PH) model was used to evaluate the effect of opium on post-op outcomes. During 133,593 person-years of follow-up, opium consumption was associated with increased risk of mortality in both patients with and without SMuRFs (weighted Hazard Ratio (HR)s: 1.248 [1.009, 1.574] and 1.410 [1.008, 2.038], respectively). There was no association between opium consumption and fatal and non-fatal MACCE in patients without SMuRF (HR = 1.027 [0.762-1.383], HR 0.700 [0.438-1.118]). Opium consumption was associated with earlier age of CABG in both groups; 2.77 (1.68, 3.85) years in SMuRF-less and 1.70 (1.11, 2.38) years in patients with SMuRFs. Opium users not only undergo CABG at younger ages but also have a higher rate of mortality regardless of the presence of traditional CAD risk factors. Conversely, the risk of MACCE is only higher in patients with at least one modifiable CAD risk factor.

424-P: Body-Weight Variability and Risk of Cardiovascular Outcomes in Type 1 Diabetes: Results from the DCCT/EDIC Studies

Cardiovascular (CV) complications are a major cause of morbimortality in long-standing type 1 diabetes (T1D) . Excessive weight gain has been associated with higher rates of CV events in the DCCT/EDIC studies. Moreover, fluctuation of body weight has emerged as an independent predictor of increased mortality and risk of CV outcomes, with evidence from the general population, from patients with coronary artery disease, and from patients with type 2 diabetes. We evaluated the association between weight fluctuation and CV events in patients with T1D from the DCCT/EDIC population. Body-weight fluctuation was measured by the average successive variability (ASV: average absolute difference between successive values) over the 9-year period of the DCCT. The primary outcome was a composite of major adverse CV events (MACE: nonfatal myocardial infarctions or cerebrovascular events, CV deaths) occurring during the first 15 years of EDIC follow-up. The risk of outcomes during follow-up was analyzed using adjusted Cox models according to tertiles of ASV. For the primary outcome, 1371 out of 1441 patients fulfilled the inclusion criteria for analysis [males: 52.41%, age: (37.53±6.82) years, mean HbA1c: (8.08±1.35) %, conventional/intensive treatment: 690/681 patients]. The cumulative incidence of MACE was 4.81%, 5.02%, and 6.58% for tertiles 1, 2, and 3, respectively (T1, T2, T3) (p=0.44) during (15.40±6.24) years of follow-up. Cox analysis adjusted for baseline EDIC characteristics (age, sex, treatment group) and time-dependent variables during DCCT (average BMI, CV risk factors, nephropathy) showed a hazard ratio (HR) for MACE of 1. (95% CI 0.58-1.92; p=0.85) for T2 and 1.34 (0.74-2.41; p=0.34) for T3, both compared to T1. For every increase of 1 standard deviation of ASV, the HR for MACE was 1. (0.86-1.42; p=0.44) . Despite a trend for a positive association, body-weight fluctuation was not significantly associated with an increased risk of MACE in patients with T1D. Disclosure I.Petria: None. S.Albuquerque: None. G.Varoquaux: None. J.Vie: None. G.Velho: None. G.Perseghin: Advisory Panel; AstraZeneca, Lilly, Merck Sharp & Dohme Corp., Novo Nordisk, PIKDARE S.p.A., Sanofi. R.Roussel: None. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi.

Estimating the causal effect of transient anemia status on renal and cardiovascular outcomes in community-dwelling patients in Japan at the beginning of impaired renal function using marginal structural modeling

BackgroundAnemia status may be transient. Causal associations between changes in anemia status over time and adverse outcome development are not well characterized in community-dwelling subjects at the beginning of impaired kidney function.MethodsThis retrospective cohort study used annual health checkup and medical and pharmacy claims data from the JMDC between January 2005 and June 2019. Community-dwelling subjects in Japan with a pre-index estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 followed by a subsequent eGFR < 60 mL/min/1.73 m2 (index) were included. The composite renal outcome was ≥ 30% eGFR reduction over 3 years from baseline, serum creatinine doubling, progression to chronic dialysis, kidney transplantation, or eGFR < 15 mL/min/1.73 m2. The composite cardiovascular outcome was fatal and non-fatal unstable angina, myocardial infarction, heart failure, or cerebrovascular event. Time-dependent anemia risk was evaluated using Breslow’s estimator and marginal structural Cox models (MSM).ResultsIn 32,870 included subjects, 1,396 had anemia at baseline. Adverse outcome incidence was higher in the baseline anemic group, but absolute differences in renal and cardiovascular outcomes between groups were diminished after adjusting for baseline characteristics. In MSM, time-dependent anemia status was associated with higher risk of renal (hazard ratio [95% confidence interval]; 2.6 [1.7–3.8]) and cardiovascular (1.6 [1.2–2.2]) outcomes and mortality (2.8 [1.8–4.3]). Absolute differences in survival probabilities were retained over time but were clinically marginal (1.1–2.7% over 6 years).ConclusionsEven in subjects at the very early stage of impaired kidney function, early detection and treatment of anemia may help reduce the development of negative sequelae.

Long-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis

BACKGROUNDPolycystic ovary syndrome (PCOS) is associated with cardiometabolic disease, but recent systematic reviews and meta-analyses of longitudinal studies that quantify these associations are lacking.OBJECTIVE AND RATIONALEIs PCOS a risk factor for cardiometabolic disease?SEARCH METHODSWe searched from inception to September 2019 in MEDLINE and EMBASE using controlled terms (e.g. MESH) and text words for PCOS and cardiometabolic outcomes, including cardiovascular disease (CVD), stroke, myocardial infarction, hypertension (HT), type 2 diabetes (T2D), metabolic syndrome and dyslipidaemia. Cohort studies and case–control studies comparing the prevalence of T2D, HT, fatal or non-fatal CVD and/or lipid concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) between women with and without PCOS of ≥18 years of age were eligible for this systematic review and meta-analysis. Studies were eligible regardless of the degree to which they adjusted for confounders including obesity. Articles had to be written in English, German or Dutch. Intervention studies, animal studies, conference abstracts, studies with a follow-up duration less than 3 years and studies with less than 10 PCOS cases were excluded. Study selection, quality assessment (Newcastle–Ottawa Scale) and data extraction were performed by two independent researchers.OUTCOMESOf the 5971 identified records, 23 cohort studies were included in the current systematic review. Women with PCOS had increased risks of HT (risk ratio (RR): 1.75, 95% CI 1.42 to 2.15), T2D (RR: 3.00, 95% CI 2.56 to 3.51), a higher serum concentration of TC (mean difference (MD): 7.14 95% CI 1.58 to 12.70 mg/dl), a lower serum concentration of HDL-C (MD: −2.45 95% CI −4.51 to −0.38 mg/dl) and increased risks of non-fatal cerebrovascular disease events (RR: 1.41, 95% CI 1.02 to 1.94) compared to women without PCOS. No differences were found for LDL-C (MD: 3.32 95% CI −4.11 to 10.75 mg/dl), TG (MD 18.53 95% CI −0.58 to 37.64 mg/dl) or coronary disease events (RR: 1.78, 95% CI 0.99 to 3.23). No meta-analyses could be performed for fatal CVD events due to the paucity of mortality data.WIDER IMPLICATIONSWomen with PCOS are at increased risk of cardiometabolic disease. This review quantifies this risk, which is important for clinicians to inform patients and to take into account in the cardiovascular risk assessment of women with PCOS. Future clinical trials are needed to assess the ability of cardiometabolic screening and management in women with PCOS to reduce future CVD morbidity.

Arterial Hypertension as a Risk Factor for Reduced Glomerular Filtration Rate after Living Kidney Donation.

Living kidney donation represents the optimal renal replacement therapy, but recent data suggest an increased long-term renal risk for the donor. Here, we evaluated the risk for reduced estimated glomerular filtration rate (eGFR), death, and major cardiovascular events such as nonfatal myocardial infarction or cerebrovascular event including TIA (transient ischemic attack) and stroke in 225 donors, who underwent pre-donation examinations and live donor nephrectomy between 1985 and 2014 at our center. The median follow-up time was 8.7 years (1.0–29.1). In multivariate analysis, age and arterial hypertension at baseline were significantly associated with a higher risk of adverse renal outcomes, such as (1) eGFR <60 mL/min/1.73 m2 (age per year: HR (hazard ratio) 1.05, 95% confidence interval (CI) 1.03–1.08, hypertension: HR 2.25, 95% CI 1.22–3.98), (2) eGFR <60 mL/min/1.73 m2 and a decrease of ≥40% from baseline (age: HR 1.08, 95% CI 1.03–1.13, hypertension: HR 4.22, 95% CI 1.72–10.36), and (3) eGFR <45 mL/min/1.73 m2 (age: HR 1.12, 95% CI 1.05–1.20, hypertension: HR 5.06, 95% CI 1.49–17.22). In addition, eGFR at time of donation (per mL/min/1.73 m2) was associated with a lower risk of (1) eGFR <60 mL/min/1.73 m2 (HR 0.98, 95% CI 0.97–1.00) and (2) eGFR <45 mL/min/1.73 m2 (HR 0.95, 95% CI 0.90–1.00). Age was the only significant predictor for death or major cardiovascular event (HR 1.08, 95% CI 1.01–1.16). In conclusion, arterial hypertension, lower eGFR, and age at the time of donation are strong predictors for adverse renal outcomes in living kidney donors.

467FFR guided acute complete revascularization versus culprit lesion only treatment in patients presenting with STEMI; 3-year cost-analysis data from COMPARE-ACUTE trial

Abstract Background Compare-Acute trial showed a 1-year superior outcome of FFR-guided acute complete revascularization (FFR-CR) compared to culprit-lesion-only revascularization (CLO) in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Long-term results and financial impact of this strategy are unknown. Purpose To evaluate if FFR-CR strategy is superior to CLO strategy in terms of health care costs at 3 year follow-up. Methods Compare-Acute is a multicenter, investigator-initiated prospective randomized controlled trial that involved 24 sites. Patients with STEMI and MVD were randomized 1:2 after successful primary PCI, towards FFR-CR or CLO treatment strategies (295 vs 590 pts). All stenosis ≥50% by angiography in the non-infarct artery were investigated by FFR in both arms. In the FFR-CR arm, all non-culprit (NC) lesions with a FFR ≤0.80 were treated by PCI. In the CLO arm pts underwent blinded FFR procedure of the NC lesions. Further treatment of these lesions was based on symptoms and/or ischemia testing during follow-up with an allowed treatment window of 45 days. The primary endpoint was defined as a composite of all-cause mortality, non-fatal myocardial infarction, any revascularization and cerebrovascular events (MACCE) at 12 months. The major secondary endpoints are MACCE and health care costs from both strategies up to 3-year follow-up. Cost-analysis is done from an insurance/governmental perspective in countries that use Diagnosis Related Group (DRG) costs: the Netherlands, Germany, Sweden and Poland. Results 1-year results have already been published and showed superior outcome of patients in the FFR-CR arm. According to the Dutch system, at 1 year of follow-up the average cost per patient was 8.150€ in the FFR-CR arm, and 10.319€ in the CLO arm (−21%). The better cost-effectiveness of FFR-CR strategy remained at 3 years of follow-up: average cost per patient was 8.653€ in the FFR-CR arm and 11.100€ in the CLO arm (−22%). Same 3-year data was confirmed using DRG analysis according to the German system (FFR-CR 4.887€ vs CLO 5.200€; −6.0%) and the Swedish system (FFR-CR 6.205€ vs CLO 8.133€; −23.7%). FFR-CR strategy was not more costly according to the Polish system (FFR-CR 3.704€ vs CLO 3.685€; +0.5%). Moreover, the better outcome of the FFR-CR group was mantained at 3 year follow-up (data not shown). Figure 1 Conclusion Our cost-analysis of the Compare Acute Trial shows that the strategy of FFR-guided complete revascularization in patients with STEMI and MVD is not only superior in terms of outcome, but also in terms of health care costs at 1 year. This benefit is maintained at 3 years follow-up.

1154FFR guided acute complete revascularization versus culprit lesion only treatment in patients presenting with STEMI and multi vessel disease; final 3-year outcome data from Compare-Acute trial

Abstract Background Compare-Acute trial showed a 1-year superior outcome of FFR-guided acute complete revascularization (FFR-CR) compared to culprit-lesion-only revascularization (CLO) in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Long-term outcome results are unknown. Purpose To evaluate if FFR-CR strategy is superior to CLO strategy in terms of outcome at 3 year follow-up. Methods Compare-Acute is a multicenter, investigator-initiated prospective randomized controlled trial that involved 24 sites. Patients with STEMI and MVD were randomized, after successful primary PCI towards FFR-CR or CLO treatment strategies with a 1:2 ratio (295 pts vs 590 pts). All stenosis ≥50% in the non-infarct artery were investigated by FFR in both arms. In the FFR-CR arm, all non-culprit (NC) lesions with a FFR ≤0.80 were treated by PCI. In the CLO arm pts underwent blinded FFR procedure of the NC lesions. Further treatment of these lesions was based on symptoms and/or ischemia testing during follow-up with an allowed treatment window of 45 days. The primary endpoint was defined as a composite of all-cause mortality, non-fatal myocardial infarction, any revascularization and cerebrovascular events (MACCE) at 12 months. The major secondary endpoint is MACCE from both strategies up to 3-year follow-up. Results 1-year clinical outcomes have already been presented and published. At 36 months the composite end-point of MACCE occurred in 46 patients in the FFR-CR group vs 178 patients in the CLO group (15.6% vs 30.2%; HR 0.46, 95% CI 0.29–0.59; p&lt;0.01), as shown in Fig. 1. The incidence of death (4 pts vs 10 pts; 1.4% vs 1.7%; HR 0.86, 95% CI 0.39–1.8; p=0.71), MI (20 pts vs 53 pts; 7.1% vs 9.3%; HR 0.74, 95% CI 0.44–1.24; p=0.25) and stroke (1 pt vs 7 pts; 0.3% vs 1.2%; HR 0.29, 95% CI 0.03–2.3; p=0.24) was not significantly different in the two groups, but revascularizations were significantly higher in the CLO group: 37 patients in the FFR-CR group vs 149 patients in the CLO group (13.0% vs 26.0%; HR 0.45; 95% CI 0.31–0.64; p&lt;0.01). Furthermore, in a subgroup analysis, when we considered only patients with FFR positive non-culprit lesions in both arms, we found a higher incidence of MI at follow-up in the CLO arm compared to the FFR-CR arm: 30/224 vs 13/194 (13.4% vs 6.7%; p 0.03). MACCE-free survival at 3 years Conclusion With this analysis of the Compare-Acute trial we confirm that the benefit of a FFR-guided complete revascularization strategy in patients with STEMI and MVD is maintained at 3 years of follow-up. This difference is mainly driven by increased revascularizations in the CLO arm, but also by increased incidence of MI in the CLO subgroup with FFR+ lesions that were left untreated.

P1251Percutaneous coronary intervention versus medical therapy for coronary lesions with positive fractional flow reserve (FFR) but preserved coronary flow reserve (CFR). A substudy of the COMPARE-ACUTE

Abstract Introduction International guidelines recommend performing percutaneous coronary intervention (PCI) on stable coronary lesions with a positive fractional flow reserve (FFR) to improve clinical outcomes. It remains unclear if FFR positive lesions with preserved coronary flow reserved (CFR) might be better treated medically. Purpose This study compared clinical outcomes between PCI and medical therapy for stable FFR-positive lesions with preserved CFR. Methods We performed a substudy of the randomized, multicenter COMPARE-ACUTE trial in which treated ST-elevation myocardial infarction patients with stable non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperaemic pressure gradients, we computed the so-called pressure bounded-CFR (pb-CFR) and classified lesions as low (&lt;2) or preserved (≥2). Our primary end point was a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events (MACCE) at 12 months. Results A total of 980 lesions from 885 subjects were included in this sub-study due to availability of baseline and hyperaemic pressure gradients. For the 462 lesions with FFR≤0.80, 249 had a pb-CFR&lt;2 while 29 had a preserved CFR (pb-CFR≥2). The rate of MACCE at 1 year did not differ significantly between subjects with FFR≤0.80 and pb-CFR&lt;2 versus FFR≤0.80 and pb-CFR≥2 (24% vs. 30%, p=0.44). Because of randomization, baseline characteristics were well balanced between subjects with FFR≤0.80 and pb-CFR≥2 who were treated by PCI or medical therapy. Importantly for subjects with FFR≤0.80 and pb-CFR≥2, MACCE occurred more frequently when treated medically compared with PCI (50% vs. 0% respectively, p=0.01). Conclusions In this post-hoc substudy from a large randomized controlled trial of 885 subjects with 980 lesions, a preserved pb-CFR≥2 did not associate with an improved clinical outcome when FFR≤0.80. Subjects with FFR-positive coronary lesions but a preserved pb-CFR experienced significantly worse clinical outcomes when treated medically instead of with PCI. These data suggest that a stenosis with a FFR≤0.80, even when pb-CFR remains preserved, benefits from treatment with PCI. Acknowledgement/Funding Maasstad Cardiovascular Research, Abbott Vascular and St. Jude Medical

TUSARC: Prognostic Value of High-Sensitivity Cardiac Troponin T Assay in Asymptomatic Patients with High Cardiovascular Risk

BackgroundPrognostic value of high-sensitivity cardiac troponin T (hs-cTnT) assays have been assessed in selected populations in different studies and in registries of members of the general population with low cardiovascular risk. The aim of this study was to determine the prognostic value of hs-cTnT in an asymptomatic very-high cardiovascular risk Spanish population. MethodsFrom a previous prospective cohort of the TUSARC (troponina T UltraSensible en pacientes Asintomáticos de alto Riesgo Cardiovascular) registry, follow-up was conducted in 602 patients (93.18%). The association of high hs-cTnT (≥99th percentile value) and incidence of primary event was studied. A primary event was defined as a combined major cardiovascular event (incidence of cardiovascular death, decompensated heart failure, non-fatal cerebrovascular event, non-fatal myocardial infarction, or coronary revascularization). The association between high hs-cTnT and incidence of secondary events was studied as well. ResultsIn patients with high hs-cTnT, the incidence of primary event during follow-up was significantly higher (18.30% vs 3.67% P < .001): heart failure (6.25% vs 0.73% P < .001), cardiovascular death (7.29% vs 0.00% P < .001), and death from any cause (7.81% vs 0.98% P < .001). ConclusionsIn an asymptomatic very-high cardiovascular risk Spanish population, elevated hs-cTnT was significantly associated with incident major cardiovascular combined end point and incidence of heart failure, cardiovascular death, and death from any cause.

Neutrophil/lymphocyte ratio in prediction of incidence of ischemic stroke in elderly persons with chronic kidney disease

Objective To investigate the relationship of the neutrophil to lymphocyte ratio (NLR) with stroke in elderly persons with CDK. Methods Totally 220 subjects with stage 3-5 CKD were followed. Fatal and nonfatal cerebrovascular event (CVE) were recorded during this period. NLR at baseline was determined from complete blood count differential. We investigated if NLR could predict stroke. Results Median NLR was 2.13. NLR was equally associated with estimated glomerular flitrationrate (eGFR). Totally 116 strokes occurred during follow-up period. NLR could predict stroke independently. Increased NLR over 2.13 was related to a significantly decreased survival time (log-rank Chi-square=4.963, P= 0.026). Multivariate Cox regression analysis showed that the risk factor of ischemic stroke in CKD patients was high NLR, hazard ratio (HR) 1.11 [95% confidence interval (CI) 1.007 to 1.223, P=0.035]. Conclusions NLR could independently predict stroke in elderly patients with moderate to severe CKD. Key words: Neutrophils/ME; Lymphocytes/ME; Kidney diseases/CO/ME; Stroke/CO/ME

Obesity and ECG left ventricular hypertrophy

Our aim was to investigate the prevalence and the prognostic significance for fatal and nonfatal cerebrovascular and cardiovascular events of different ECG criteria for left ventricular hypertrophy (LVH) in normal weight, overweight and obese patients in an adult Italian population. A total of 18 330 adults (mean age 54 ± 11 years, 55% women, 53% hypertensive patients) were analyzed from the Moli-sani cohort. Obesity was defined using the ATPIII criteria. ECG-LVH was defined according to 2013 ESC-ESH guidelines. The age and sex adjusted prevalence of ECG-LVH did not differ from normal weight patients to class 1-3 obesity patients, when Cornell-voltage criterion was used. In overweight and obese patients, as compared with normal weight patients, a progressively lower prevalence of ECG-LVH was observed when the Sokolow-Lyon index was used, whereas a higher prevalence was shown by using the aVL R-wave voltage (>11 and >5.7 mm) and the Cornell-voltage-QRS duration product. The incidence of cardiovascular events was significantly greater in patients with ECG LVH diagnosis by the Cornell voltage [hazard ratio 1.89, 95% confidence interval (CI) 1.05-3.39] and the Cornell product (hazard ratio 1.87, 95% CI 1.31-2.67). After adjusting for different confounders (age, sex, cigarette, hypertension, hypercholesterolemia, diabetes, income, education, occupational class and physical activity) and for BMI categories, only the Cornell product remained significantly associated with a higher incidence of cardiovascular events (hazard ratio 1.66; 95% CI 1.16-2.38). The predictive significance of different LVH criteria was assessed across BMI categories; after adjusting for confounders, no LVH criteria were significantly associated with an increased risk of cardiovascular events in obese patients; Cornell-product LVH remained an independent predictor of events in normal weight and overweight individuals (hazard ratio 2.63; 95% CI 1.10-6.28 and hazard ratio 2.72; 95% CI 1.52-4.25, respectively). Our results confirm that ECG LVH prevalence may differ according to the criteria used across BMI categories in a low cardiovascular risk cohort. The use of different LVH criteria according to BMI categories may improve cardiovascular risk stratification in a general population independently of several confounding factors.

Evaluation of the Incidence of Major Adverse Cardiac and Cerebrovascular Events after Percutaneous Coronary Intervention or Coronary Artery Bypass Graft on Proximal Left Anterior Descending Artery with and without Other Coronary Arteries Involvement

: Background: Major Adverse Cardiac and Cerebrovascular Events (MACCE) include cardiac death, nonfatal Myocardial Infarction (MI), cerebrovascular events, and Target Vessel Revascularization (TVR) that may happen after Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft (CABG). Objectives: This study aimed to compare the incidence of MACCE between the patients who underwent PCI or CABG due to significant Left Anterior Descending (LAD) stenosis with and without other coronary arteries involvement. Patients and Methods: This randomized mixed cohort study was conducted on 400 patients with Coronary Artery Disease (CAD), 200 with proximal LAD stenosis and 200 with non-proximal LAD stenosis, selected through census. Half of each group underwent PCI and the rest underwent CABG. The participants were followed at fixed intervals after the procedure and the incidence of MACCE was documented in their checklists. Then, relative risk index was used to compare the two groups regarding the incidence of MACCE. Statistical analysis was done using the Stata software, version 11 and P Results: The study participants included 281 males and 119 females with the mean age of 61.36 ± 10.66 years. The results showed a significant difference between the two groups regarding the incidence of MACCE (31.58% vs. 3%, P = 0.001). However, no significant difference was found between the effects of PCI with drug eluting stent and CABG on proximal LAD (3.70% vs. 3%, P = 1.00). Conclusions: Considering the incidence of MACCE, CABG had no superiority over DES for proximal LAD stenosis.

Impact of candesartan on cardiovascular events after drug-eluting stent implantation in patients with coronary artery disease: The 4C trial

ObjectiveThe purpose of this study was to examine the cardiovascular protective effects of candesartan in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). BackgroundCandesartan has been reported to reduce cardiovascular events when therapy was started 6 months after PCI with bare-metal stents in patients who survived restenosis. Candesartan started immediately after PCI with DESs was also effective in preventing cardiovascular events. MethodsThe 4C trial was a multicenter, prospective, randomized, open-label study. A total of 1145 patients at 39 centers in Japan were randomly assigned to receive candesartan plus standard medical treatment or standard medical treatment alone. The primary endpoints were all-cause death, and a composite of non-fatal myocardial infarction (MI), unstable angina pectoris (uAP), congestive heart failure (CHF), and non-fatal cerebrovascular events. The follow-up period was up to 3 years after the index PCI (ClinicalTrials.gov NCT00139386). ResultsThe incidence of total death, one of the primary endpoints, was comparable between the two treatment groups (3.8% each, p=0.9702). Another primary endpoint, non-fatal major cardiovascular events, tended to occur more often in the control group than in the candesartan group (9.2% vs. 12.5%, p=0.0985). In contrast, candesartan significantly reduced one of the pre-specified secondary endpoints: cardiovascular events that included non-fatal MI, uAP, and CHF (4.4% vs. 6.7%, p=0.0136). Furthermore, candesartan significantly reduced another secondary endpoint that included cardiovascular events and cardiovascular death (5.0% vs. 7.7%, p=0.0493). ConclusionsThe 4C trial showed that candesartan administered immediately after PCI with DESs did not improve the prognosis after the index procedure, but did reduce some cardiac-related events for 3 years.

How Many Measurements Are Needed to Estimate Blood Pressure Variability Without Loss of Prognostic Information?

Average real variability (ARV) is a recently proposed index for short-term blood pressure (BP) variability. We aimed to determine the minimum number of BP readings required to compute ARV without loss of prognostic information. ARV was calculated from a discovery dataset that included 24-hour ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5% women) of Copenhagen, Denmark. Concordance between ARV from full (≥80 BP readings) and randomly reduced 24-hour BP recordings was examined, as was prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0 years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited population cohorts was used to validate the results. In the discovery dataset, a minimum of 48 BP readings allowed an accurate assessment of the association between cardiovascular risk and ARV. In the test dataset, over 10.2 years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac deaths) and 696 experienced a major fatal or nonfatal cardiovascular event. Standardized multivariable-adjusted hazard ratios (HRs) were computed for associations between outcome and BP variability. Higher diastolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17), and cardiac (HR = 1.24) mortality. Forty-eight BP readings over 24 hours were observed to be adequate to compute ARV without meaningful loss of prognostic information.

Comparison between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Risk of Stroke Recurrence and Longitudinal Progression of White Matter Lesions and Silent Brain Infarcts on MRI (CEREBRAL Study): Rationale, Design, and Methodology

Patients with a history of ischemic stroke are known to develop new ischemic stroke. While asymptomatic, the presence and progression of silent brain infarcts and white matter lesions on magnetic resonance imaging are associated with an increased risk of future strokes. Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are recommended for the primary and secondary prevention of stroke, but there are no direct comparisons of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers regarding their cerebroprotective effects, including their effect on asymptomatic cerebral lesions detected by magnetic resonance imaging. Elderly (65 years or older) patients with essential hypertension who underwent cerebral magnetic resonance imaging and were found to have any cerebral ischemic lesions, such as cerebral infarction, silent brain infarct, or white matter lesion, were enrolled in this CEREBRAL study. Patients who agreed to participate were enrolled in the randomized controlled trial portion. Patients who did not agree to participate in the randomized controlled trial were enrolled in the cohort study portion. After two-years of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers treatment, follow-up magnetic resonance imaging examination will be performed. The primary end-point is the composite of (1) occurrence of a fatal or nonfatal cerebrovascular event or (2) progression of cerebrovascular lesions as evaluated by magnetic resonance imaging, including white matter lesions or silent brain infarcts. After enrollment, cognitive function was evaluated, if possible, using the Mini-Mental State Examination. Our study will clarify whether angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are more effective for preventing primary and recurrence of ischemic stroke, including the progression of asymptomatic cerebral lesions on magnetic resonance imaging, in elderly hypertensive patients.

Media-to-lumen ratio as predictor of renal abnormalities in hypertension: new findings, new questions

Media-to-lumen ratio as predictor of renal abnormalities in hypertension: new findings, new questions

Combined effect of albuminuria and estimated glomerular filtration rate on cardiovascular events and all-cause mortality in uncomplicated hypertensive patients

Decreased glomerular filtration rate (GFR) and microalbuminuria predict cardiovascular events and mortality in the general population and in high-risk patients. Their combined prognostic power in low-risk patients has never been reported. We assessed the prognostic role of GFR and albuminuria for cardiovascular disease and all-cause mortality in nondiabetic patients with primary hypertension. We conducted an 11.2-year follow-up of 837 uncomplicated hypertensive patients enrolled in the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) cohort between 1993 and 1997. Urinary albumin-to-creatinine ratio (ACR) and estimated GFR (eGFR) were assessed in untreated patients at baseline. Renal dysfunction was defined as the inclusion in the most unfavorable sex-specific decile of eGFR or of ACR. The primary endpoints were the occurrence of fatal and nonfatal cerebrovascular and cardiac events (CVEs), composite of nonfatal cerebrovascular and cardiac events (CVD) and all-cause death (CEP), and composite of CVD and chronic renal insufficiency (CRE). During 9374 person-years of follow-up, the incidence rate for CVE, CRE, and all-cause mortality was 6.3, 7.8, and 3.1 /1000 person-years, respectively. Renal dysfunction was associated with increased risk for CVE [relative risk (RR) 2.13, 95% confidence interval (CI) 1.15-3.93, P = 0.011], CEP (RR 1.78, 95% CI 1.02-3.08, P = 0.027), and CRE (RR 2.47, 95% CI 1.45-4.29, P < 0.001), even after adjusting for several baseline covariates such as sex, duration and severity of blood pressure, and total cholesterol. Renal dysfunction is a risk factor for cardiorenal events and all-cause mortality, regardless of traditional confounders, in uncomplicated patients with primary hypertension.

Management of Blood Pressure for Acute and Recurrent Stroke

Marc Fisher MD Kennedy Lees MD Section Editors: Hypertension is the most important modifiable risk factor for stroke.1,2 It is estimated that 25% or more of strokes may be attributable to hypertension. Because many patients with stroke have mild hypertension or prehypertension, we have shifted our focus and now think of stroke on a continuum of risk based on blood pressure (BP) level rather than on a threshold effect.3 Because high BP may not exist in isolation, a wider definition of hypertension has been proposed that also takes into account the absolute risk of cardiovascular events and associated metabolic factors or early disease markers.3 Lowering BP reduces the risk of stroke. Epidemiological studies have shown that for each 10 mm Hg lower systolic blood pressure (SBP), there is a decrease in risk of stroke of approximately one third in persons aged 60 to 79 years. This association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, stroke subtypes, and for fatal and nonfatal events.4 Lowering diastolic blood pressure (DBP) was once the main target to achieve stroke and other cardiovascular event reduction, but SBP has now become the target.3 As recently shown, even the elderly with sustained SBP elevation may gain from BP reduction in relation to less fatal or nonfatal stroke, death, and heart failure.5 Although the role of longer-term BP control to improve outcomes in patients with stroke is undisputed, BP management immediately after a stroke remains controversial. In an effort to resolve this controversy, several pilot clinical trials have been initiated. In this review, we discuss the results of some of these trials and available evidence-based guidelines for BP control in the settings of acute ischemic and hemorrhagic stroke (excluding subarachnoid hemorrhage) and …

Association of Antiplatelet Therapy With Lower Risk of Death and Recurrent Cerebrovascular Events After Ischemic Stroke

Evidence of the beneficial effects of antiplatelet therapy after ischemic stroke is currently lacking in China. Demographic data, pre-stroke risk factors, severity of neurological deficit, and disability graded by the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) of 1,951 patients were measured and recorded at baseline. Regular follow-up by interview was performed for 12 months post-recruitment. The all-cause mortality was 1.88 per 100 person-years during the follow-up period. Recurrent fatal and nonfatal cerebrovascular events occurred in 90 patients, accounting for 4.24 per 100 person-years of cumulative incidence. After adjustment by other variables, antiplatelet therapy was identified as an independent protective predictor of all-cause death (hazard ratio (HR) 0.42; 95% confidence interval (CI) 0.21-0.86; P=0.017) and recurrent cerebrovascular events (HR 0.58; 95%CI 0.36-0.92; P=0.021). Among survivors, antiplatelet therapy was also an independent predictor for improvement in the NIHSS (HR 1.27; 95%CI 1.07-1.51; P=0.006) and the MRS (HR 1.25; 95%CI 1.02-1.52; P=0.031). The data from this multicenter, prospective study confirmed the association between antiplatelet therapy and decreased risk of all-cause mortality and recurrent cerebrovascular events after ischemic stroke in Chinese patients.

Lipoprotein(a), Hormone Replacement Therapy, and Risk of Future Cardiovascular Events

This study assesses whether the relationship of lipoprotein(a) [Lp(a)] with cardiovascular risk may be modified by concurrent hormone replacement therapy (HT). Prior studies indicate that HT decreases plasma levels of Lp(a), but few have been powered to assess whether it modifies the relationship of Lp(a) with cardiovascular disease (CVD). Lipoprotein(a) at baseline was measured among 27,736 initially healthy women, of whom 12,075 indicated active HT use at the time of blood draw at study initiation and 15,661 did not. The risk of first-ever major cardiovascular event (nonfatal myocardial infarction, nonfatal cerebrovascular event, coronary revascularization, or cardiovascular death) over a 10-year period was assessed with Cox proportional hazard models according to Lp(a) levels and HT status and adjusted for potential confounding variables. As anticipated, Lp(a) values were lower among women taking HT (median 9.4 mg/dl vs. 11.6 mg/dl, p < 0.0001). In women not taking HT, the hazard ratio of future CVD for the highest Lp(a) quintile compared with the lowest was 1.8 (p trend <0.0001), after adjusting for age, smoking, blood pressure, diabetes, body mass index, total cholesterol, high-density lipoprotein, C-reactive protein, and treatment arms of aspirin and vitamin E. In contrast, among women taking HT, there was little evidence of association with CVD (hazard ratio: 1.1, p trend = 0.18; interaction p value = 0.0009 between Lp(a) quintiles and HT on incident CVD). The relationship of high Lp(a) levels with increased CVD is modified by HT. These data suggest that the predictive utility of Lp(a) is markedly attenuated among women taking HT and may inform clinicians' interpretation of Lp(a) values in such patients. (Women's Health Study [WHS]; NCT00000479).