Shaw, Leslee J.

Abstract Aims To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). Methods and results We analyzed mild stenosis (25–49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02–3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09–2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07–2.22; P = 0.020). Conclusion In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. Clinical trial registration ClinicalTrials.gov NCT02803411

Cardiovascular (CV) disease (CVD) is the major health burden and cause of death for women. Marked disparities exist in CVD diagnosis, prevention, and treatment between women and men – as well as lack of female-specific data. Population, physiologic, translational, and clinical trial studies of sex and gender differences in CVD [[Unable to Display Character: –]] even when only women are studied[[Unable to Display Character: –]] often do not collect relevant data specific to women that could inform study outcomes. The ISIS CVD Network of the Society for Women’s Health Research compiled an inventory of items specific for women across the lifespan, together with references for methods and strategies to gather and evaluate this information; some items comprise robust measures, others are in development. The objective is to enhance usefulness of CVD research data in understanding sex and gender differences, thereby optimizing healthcare delivery and outcomes for women. Included are hormonal variables (menstrual cycle phase, hormone levels) oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, measures of menopause, and menopausal hormone therapy, variables generally not collected in research studies, but essential to determine their role as sex-specific contributors to CV health and disease. Clear associations exist between reproductive health and CV health and disease. For example 25-33% of women experience complications of pregnancy that may precede and predispose to CVD. Vascular complications during pregnancy, antecedent risk factors and subsequent clinical CVD can be ascertained using medical records, birth registries, and/or maternal recall. Evaluating compilations of patient data with known hormonal or menopausal status using reference standards and patient data for PCOS could inform relationships to subsequent CV outcomes. Variables predominant among women that preferentially disadvantage them should be considered; e.g. psychosocial issues and elderly age. Depressive disorders are twice as common among women as men. They adversely affect CVD outcomes in women, yet the effect of reproductive life cycle and of hormonal fluctuations on depression and etiologic contributions of depression to CVD are inadequately explored. In addition to traditional CVD risk factors, diabetes mellitus, chronic inflammatory disorders, oxidative stress, vasomotor dysfunction, coronary microvascular disorders, and other novel risk variables that preferentially impact women should be explored. Along with increased enrollment of women in CVD research studies and analysis of clinical and genetic studies by sex, improvements and expansion of study design must include these understudied uniquely or predominantly female characteristics. This will enhance the quality and quantity of evidence-based medicine to guide CVD care in women and men thereby setting the stage for personalized approach to medicine.

Background There are few data comparing clinical outcome and potential indications for routine post–myocardial infarction cardiac catheterization and revascularization of patients who sustain a non–Q-wave versus Q-wave infarct after thrombolytic therapy. Methods and Results A secondary analysis of 2634 patients enrolled in the TIMI II trial with a first myocardial infarction was performed to determine 6-week and 1-year cardiac event rates and identify clinical and angiographic differences between the 1867 patients (70.9%) who evolved a Q-wave infarct and the 767 patients (29.1%) who sustained a non–Q-wave infarct after treatment with intravenous thrombolytic therapy. Male sex (85.3% versus 75.6%; P <.001) and anterior wall infarcts (53.8% versus 43.7%; P <.001) were more frequent in the Q-wave versus the non–Q-wave group. During recombinant tissue-type plasminogen activator (rTPA) infusion, a greater percentage of non–Q-wave patients (37.3% versus 23.5%; P =.001) had normalization of initial ST-segment elevation. Infarct-related artery patency (TIMI flow grade 2 or 3) ( P =.02), complete infarct-related artery reperfusion (TIMI 3 flow grade) ( P <.001), and the percentage of patients with a predischarge resting left ventricular ejection fraction >55% ( P <.001) were greater in the non–Q-wave group. New congestive heart failure during hospitalization developed more frequently in Q-wave patients (18.9% versus 11.6%; P <.001). After 42 days, the occurrences of reinfarction ( P =.76), death ( P =.76), and combined death or reinfarction ( P =.43) were similar in patients assigned to the invasive or conservative postlytic management strategy, regardless of infarct type. One-year mortality was 3.4% versus 4.4% for non–Q-wave versus Q-wave infarct type, respectively ( P =.25). Conclusions Angiographic and clinical differences were observed between patients who present with initial ST-segment elevation and evolve early non–Q-wave versus Q-wave myocardial infarcts after treatment with rTPA, heparin, and aspirin. Early mortality and adverse clinical cardiac events in these patients are not significantly different after a conservative compared with an invasive treatment strategy, regardless of whether the infarct type is non–Q wave or Q wave.

Background— There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. Methods and Results— We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P =0.59). Compared with ETT, index testing costs were higher for exercise MPI ( P <0.001), whereas downstream procedural costs were slightly lower ( P =0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI ( P <0.001). Conclusions— In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00282711.