Sex differences in coronary artery disease severity and mortality: the impact of conventional cardiovascular risk factors

It is still unknown whether traditional risk factors may have a sex specific impact on the severity of coronary artery disease (CAD) and subsequent mortality in acute coronary syndromes (ACS). We identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC (NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between conventional risk factors and severity of CAD and its relationship with 30-day mortality. Risk ratios (RRs) and 95% CIs were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Severity of disease was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD, specifically Ischemia and No Obstructive Coronary Artery disease (INOCA) and Myocardial Infarction with Non obstructive Coronary Arteries (MINOCA). The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49(95%CI,0.41–0.60) and among those with diabetes mellitus was 0.89(95% CI,0.62–1.29), with an interaction by diabetes mellitus status of P =0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41–0.61) in nonsmokers to 0.75 (95%CI, 0.54–1.03) in current smokers, with an interaction by smoking status of P=0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR, 1.75; 95% CI, 1.48–2.07). No sex differences in mortality were observed in patients with INOCA/MINOCA. In conclusion, obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions.

Medial Artery Calcification (MAC) e Small Artery Disease (SAD) nei pazienti con ischemia critica degli arti inferiori: definizione dei fattori predisponenti, svilup-po di uno score prognostico, definizione istopatologica e valutazione dei risultati dell'arterializzazione delle vene dell'arto inferiore come tecnica di rivascolarizzazione

Questo studio si concentra sull'ischemia critica cronica dell'arto inferiore (CLTI), una patologia globale con gravi complicanze e impatto sociale elevato. Recentemente, la "Medial Artery Calcification" (MAC) è emersa come fattore prognostico significativo nei pazienti con CLTI e malattia grave dei vasi del piede, ma le informazioni sono principalmente retrospettive. Questa tesi esplora la relazione tra MAC e CLTI in tre sezioni. Nella sezione clinica, 248 pazienti sono stati divisi in gruppi MAC per valutare l'impatto prospettico sulla guarigione e sul salvataggio dell'arto. Nella sezione isto-patologica, campioni arteriosi di 26 pazienti sottoposti ad amputazione maggiore sono stati analizzati per comprendere la relazione tra MAC, aterosclerosi e occlusione vascolare. Nella sezione di arterializzazione, 16 pazienti sottoposti all'arterializzazione delle vene del piede (AVP) sono stati esaminati per valutare i risultati clinici prospettici. I risultati della sezione clinica indicano che la presenza di MAC severa è associata a risultati clinici peggiori nei pazienti affetti da CLTI. L'analisi isto-patologica mostra una prevalenza elevata di MAC rispetto all'aterosclerosi, con una associazione importante tra MAC e iperplasia intimale. L'AVP presenta risultati promettenti nei pazienti affetti da CLTI. In conclusione, la MAC influisce sui risultati clinici della CLTI, e l'AVP potrebbe essere una strategia efficace di trattamento.

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

Cystic adventitial disease of the popliteal artery: an argument for the developmental theory

Cystic adventitial disease is a rare non-atheromatous cause of popliteal artery disease. We report a case of a 54-year-old patient with claudication of the right calf caused by cystic adventitial disease. Intra-operatively, a communication between the adventitia and the knee joint was identified. Connections between the adventitial cyst and the nearby joint have been reported in the literature that support the developmental theory. This theory suggests that cystic adventitial disease is a developmental manifestation of mucin-secreting cells derived from the mesenchyme of the adjacent joint. This case is the first, to our knowledge, in which a communication between joint and adventitia has been clearly documented by operative findings.

ECG scar quantification correlates with cardiac magnetic resonance scar size and prognostic factors in Chagas' disease

Objective To test the hypothesis that 12-lead ECG QRS scoring quantifies myocardial scar and correlates with disease severity in Chagas' heart disease. Design Patients underwent 12-lead ECG for QRS scoring and cardiac magnetic resonance with late gadolinium enhancement (CMR-LGE) to assess myocardial scar. Setting University of Sao Paulo Medical School, Sao Paulo, Brazil. Patients 44 Seropositive patients with Chagas' disease without a history of myocardial infarction and at low risk for coronary artery disease. Main outcome measures Correlation between QRS score, CMR-LGE scar size and left ventricular ejection fraction. Relation between QRS score, heart failure (HF) class and history of ventricular tachycardia (VT). Results QRS score correlated directly with CMR-LGE scar size (R=0.69, p<0.0001) and inversely with left ventricular ejection fraction (R=-0.54, p=0.0002), which remained significant in the subgroup with conduction defects. Patients with class II or III HF had significantly higher QRS scores than those with class I HF (5.1 +/- 3.4 vs 2.1 +/- 3.1 QRS points (p=0.002)) and patients with a history of VT had significantly higher QRS scores than those without a history of VT (5.3 +/- 3.2% vs 2.6 +/- 3.4 QRS points (p=0.02)). A QRS score >= 2 points had particularly good sensitivity and specificity (95% and 83%, respectively) for prediction of large CMR-LGE, and a QRS score >= 7 points had particularly high specificity (92% and 89%, respectively) for predicting significant left ventricular dysfunction and history of VT. Conclusions The wide availability of 12-lead ECG makes it an attractive screening tool and may enhance clinical risk stratification of patients at risk for more severe, symptomatic Chagas' heart disease.

Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery

Background: Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment. Methods: Patients (611) with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT). After 5-year follow-up, 392 patients (64%) underwent new angiography. Progression was considered a new stenosis of >= 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels. Results: Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84%) compared with CABG (57%) and MT (74%) patients (p < 0.001). LAD coronary territory had higher progression compared with LCX and RCA (P < 0.001). PCI treatment, hypertension, male sex, and previous MI were independent risk factors for progression. No statistical difference existed between coronary events and the development of progression. Conclusion: The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.

Quality of life after coronary artery bypass surgery

This study assessed the quality of life (QoL) of 124 people with coronary artery disease who had coronary artery bypass surgery in a hospital in Brazil, by using the Modified Flanagan`s QoL instrument as the outcome measure. In addition, we studied the association between QoL and demographic, clinical, and perceived health status (using SF-36 Health Survey) measures. The mean for the Modified Flanagan`s QoL was high (M = 84.8, SD = 13.6) when compared to similar studies in the United States. In a linear regression analysis, the SF-36 subscales of vitality, and general and mental health were statistically significant (p < .01 for all), after adjusting for other demographic and clinical variables. Increasing values of those SF-36 subscales corresponded to increasing Modified Flanagan`s QoL. Despite the limitations of the study, this result suggests that future clinical interventions aimed to improve QoL in this population could focus on the patient`s psychological conditions after the surgery.

Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy

Background: Periodontal disease shares risk factors with cardiovascular diseases and other systemic inflammatory diseases. The present study was designed to assess the circulating matrix metalloproteinases (MMPs) from chronic periodontal disease patients and, subsequently, after periodontal therapy. Methods: We compared the plasma concentrations of MMP-2. MMP-3, MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and total gelatinolytic activity in patients with periodontal disease (n =28) with those of control subjects (n = 22) before and 3 months after non-surgical periodontal therapy. Results: Higher plasma MMP-3, MMP-8, and MMP-9 concentrations were found in periodontal disease patients compared with healthy controls (all P<0.05), whereas MMP-2, TIMP-1, and TIMP-2 levels were not different. Treatment decreased plasma MMP-8 and MMP-9 concentrations by 35% and 39%, respectively (both P<0.02), while no changes were found in controls. MMP-2, MMP-3, TIMP-1, and TIMP-2 remained unaltered in both groups. Plasma gelatinolytic activity was higher in periodontal disease patients compared with controls (P<0.001) and decreased after periodontal therapy (P<0.05). Conclusions: This study showed increased circulating MMP-8 and MMP-9 levels and proteolytic activity in periodontal disease patients that decrease after periodontal therapy. The effects of periodontal therapy suggest that it may attenuate inflammatory chronic diseases. (C) 2009 Published by Elsevier B.V.

Cardiac MRI for Detection of Unrecognized Myocardial Infarction in Patients With End-Stage Renal Disease: Comparison With ECG and Scintigraphy

OBJECTIVE. The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI. SUBJECTS AND METHODS. We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI. RESULTS. Fifty-six patients (78%) were men ( mean age, 56.2 +/- 9.4 years) and 16 (22%) were women ( mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% ( not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis. CONCLUSION. Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.

Prognostic Value of Dobutamine Stress Echocardiography With Early Injection of Atropine With Versus Without Chronic Beta-Blocker Therapy in Patients With Known or Suspected Coronary Heart Disease

Although a new protocol of dobutamine stress echocardiography with the early injection of atropine (EA-DSE) has been demonstrated to be useful in reducing adverse effects and increasing the number of effective tests and to have similar accuracy for detecting coronary artery disease (CAD) compared with conventional protocols, no data exist regarding its ability to predict long-term events. The aim of this study was to determine the prognostic value of EA-DSE and the effects of the long-term use of beta blockers on it. A retrospective evaluation of 844 patients who underwent EA-DSE for known or suspected CAD was performed; 309 (37%) were receiving beta blockers. During a median follow-up period of 24 months, 102 events (12%) occurred. On univariate analysis, predictors of events were the ejection fraction (p <0.001), male gender (p <0.001), previous myocardial infarction (p <0.001), angiotensin-converting enzyme inhibitor therapy (p = 0.021), calcium channel blocker therapy (p = 0.034), and abnormal results on EA-DSE (p <0.001). On multivariate analysis, the independent predictors of events were male gender (relative risk [RR] 1.78, 95% confidence interval [CI] 1.13 to 2.81, p = 0.013) and abnormal results on EA-DSE (RR 4.45, 95% CI 2.84 to 7.01, p <0.0001). Normal results on EA-DSE with P blockers were associated with a nonsignificant higher incidence of events than normal results on EA-DSE without beta blockers (RR 1.29, 95% CI 0.58 to 2.87, p = 0.54). Abnormal results on EA-DSE with beta blockers had an RR of 4.97 (95% CI 2.79 to 8.87, p <0.001) compared with normal results, while abnormal results on EA-DSE without beta blockers had an RR of 5.96 (95% CI 3.41 to 10.44, p <0.001) for events, with no difference between groups (p = 0.36). In conclusion, the detection of fixed or inducible wall motion abnormalities during EA-DSE was an independent predictor of long-term events in patients with known or suspected CAD. The prognostic value of EA-DSE was not affected by the long-term use of beta blockers. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1291-1295)

Coronary Artery Stenoses: Accuracy of 64-Detector Row CT Angiography in Segments with Mild, Moderate, or Severe Calcification-A Subanalysis of the CORE-64 Trial

Purpose: To evaluate the influence of cross-sectional arc calcification on the diagnostic accuracy of computed tomography (CT) angiography compared with conventional coronary angiography for the detection of obstructive coronary artery disease (CAD). Materials and Methods: Institutional Review Board approval and written informed consent were obtained from all centers and participants for this HIPAA-compliant study. Overall, 4511 segments from 371 symptomatic patients (279 men, 92 women; median age, 61 years [interquartile range, 53-67 years]) with clinical suspicion of CAD from the CORE-64 multi-center study were included in the analysis. Two independent blinded observers evaluated the percentage of diameter stenosis and the circumferential extent of calcium (arc calcium). The accuracy of quantitative multidetector CT angiography to depict substantial (>50%) stenoses was assessed by using quantitative coronary angiography (QCA). Cross-sectional arc calcium was rated on a segment level as follows: noncalcified or mild (<90 degrees), moderate (90 degrees-180 degrees), or severe (>180 degrees) calcification. Univariable and multivariable logistic regression, receiver operation characteristic curve, and clustering methods were used for statistical analyses. Results: A total of 1099 segments had mild calcification, 503 had moderate calcification, 338 had severe calcification, and 2571 segments were noncalcified. Calcified segments were highly associated (P < .001) with disagreement between CTA and QCA in multivariable analysis after controlling for sex, age, heart rate, and image quality. The prevalence of CAD was 5.4% in noncalcified segments, 15.0% in mildly calcified segments, 27.0% in moderately calcified segments, and 43.0% in severely calcified segments. A significant difference was found in area under the receiver operating characteristic curves (noncalcified: 0.86, mildly calcified: 0.85, moderately calcified: 0.82, severely calcified: 0.81; P < .05). Conclusion: In a symptomatic patient population, segment-based coronary artery calcification significantly decreased agreement between multidetector CT angiography and QCA to detect a coronary stenosis of at least 50%.

Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery

Incomplete revascularization is associated with worse long-term outcomes. Autologous bone marrow cells (BMC) have recently been tested in patients with severe coronary artery disease. We tested the hypothesis that intramyocardial injection of autologous BMC increases myocardial perfusion in patients undergoing incomplete coronary artery bypass grafting (CABG). Twenty-one patients (19 men), 59 +/- 7 years old, with limiting angina and multivessel coronary artery disease (CAD), not amenable to complete CABG were enrolled. BMC were obtained prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing 2.1 +/- 1.3 x 10(8) BMC (CD34+ = 0.8 +/- 0.3%) were injected in the ischemic non-revascularized myocardium. Myocardial perfusion was assessed by magnetic resonance imaging (MRI) at baseline and 1 month after surgery. The increase in myocardial perfusion was compared between patients with < 50% (group A, n = 11) with that of patients with > 50% (group B, n = 10) of target vessels (stenosis a parts per thousand yenaEuro parts per thousand 70%) successfully bypassed. Injected myocardial segments included the inferior (n = 12), anterior (n = 7), and lateral (n = 2) walls. The number of treated vessels (2.3 +/- 0.8) was significantly smaller than the number of target vessels (4.2 +/- 1.0; P < 0.0001). One month after surgery, cardiac MRI showed a similar reduction (%) in the ischemic score of patients in group A (72.5 +/- 3.2), compared to patients in group B (78.1 +/- 3.2; P = .80). Intramyocardial injection of autologous BMC may help increase myocardial perfusion in patients undergoing incomplete CABG, even in those with fewer target vessels successfully treated. This strategy may be an adjunctive therapy for patients suffering from a more advanced (diffuse) CAD not amenable for complete direct revascularization.

Association between ADAMTS13 polymorphisms and risk of cardiovascular events in chronic coronary disease

Introduction: Association between ADAMTS13 levels and cardiovascular events has been described recently. However, no genetic study of ADAMTS13 in coronary patients has been described. Materials and Methods: Based on related populations frequencies and functional studies, we tested three ADAMTS13 polymorphisms: C1342G (Q448E), C1852G (P618A) and C2699T (A900V) in a group of 560 patients enrolled in the Medical, Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. The incidence of the 5-year end-points of death and death from cardiac causes, myocardial infarction, refractory angina requiring revascularization and cerebrovascular accident was determined for each polymorphim`s allele, genotype and haplotype. Risk was assessed with the use of logistic regression and Cox proportional-hazards model and multivariable adjustment was employed for possible confounders. Results: Clinical characteristics and received treatment of each genotype group were similar at baseline. In an adjusted model for cardiovascular risk variables, we were able to observe a significant association between ADAMTS13 900V variant and an increased risk of death (OR: 1,92 CI: 1,14-3,23, p = 0,015) or death from cardiac cause (OR: 2,67, CI: 1,59-4,49, p = 0,0009). No association between events and ADAMTS13 Q448E or P618A was observed. Conclusions: This first report studying the association between ADAMTS13 genotypes and cardiovascular events provides evidence for the association between ADAMTS13 900V variant and an increased risk of death in a population with multi-vessel CAD. (C) 2009 Elsevier Ltd. All rights reserved.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background-The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P = 0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P = 0.76). In the coronary artery bypass grafting stratum (n = 763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P = 0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P = 0.010) and cardiac death or MI (P = 0.03) were also less frequent. Reduction in MI (P = 0.001) and cardiac death/MI (P = 0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305. (Circulation. 2009;120:2529-2540.)