New Scope of the Document Although reports on cardiovascular screening efficacy have predominantly involved populations of adolescents and young adults participating in competitive athletics, the ...context of the present discussion is intentionally (and necessarily) much more expansive. ...it is underscored that the present report is not limited in scope to universal mass screening for athlete populations but importantly includes considerations for screening large, young, and truly general populations (school-aged, 12-25 years old, of both sexes) with respect to relevant logistical, ethical, legal, and societal issues (e.g., in the United States or other countries or communities of various sizes, in schools, or in regional or military populations).
Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular events, especially in high-risk populations.
This study sought to evaluate the influence of LDL-C on ...the incidence of cardiovascular events either following a coronary revascularization procedure (percutaneous coronary intervention PCI or coronary artery bypass grafting CABG) or optimal medical therapy alone in patients with established coronary heart disease and type 2 diabetes (T2DM).
Patient-level pooled analysis of 3 randomized clinical trials was undertaken. Patients with T2DM were categorized according to the levels of LDL-C at 1 year following randomization. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE the composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke).
A total of 4,050 patients were followed for a median of 3.9 years after the index 1-year assessment. Patients whose 1-year LDL-C remained ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE (17.2% vs. 13.3% vs. 13.1% for LDL-C between 70 and <100 mg/dl and LDL-C <70 mg/dl, respectively; p = 0.016). When compared with optimal medical therapy alone, patients with PCI experienced a MACCE reduction only if 1-year LDL-C was <70 mg/dl (hazard ratio: 0.61; 95% confidence interval: 0.40 to 0.91; p = 0.016), whereas CABG was associated with improved outcomes across all 1-year LDL-C strata. In patients with 1-year LDL-C ≥70 mg/dl, patients undergoing CABG had significantly lower MACCE rates as compared with PCI.
In patients with coronary heart disease with T2DM, lower LDL-C at 1 year is associated with improved long-term MACCE outcome in those eligible for either PCI or CABG. When compared with optimal medical therapy alone, PCI was associated with MACCE reductions only in those who achieved an LDL-C <70 mg/dl.
...in a population of patients with T2D and stable ischemic heart disease, we found that the lower concentrations of hsTnT observed in women were nonetheless associated with an elevated risk of major ...CV events and death compared with men with similar hsTnT levels.
Myocardial infarction in nonobstructive coronary artery disease (MINOCA) is a recently described infarct subtype. There are few studies that examine coronary artery disease (CAD) extent, MI size and ...type, and treatment differences at hospital discharge compared to myocardial infarction in obstructive coronary artery disease (MICAD), or that explore sex-specific MINOCA attributes of coronary anatomy and infarct size.
Our study population consisted of a single tertiary-center of consecutive patients that had coronary angiography for acute MI between 2005 and 2015. The MI type at presentation, MI size and ejection fraction (post-MI), and gender differences between MINOCA patients were examined.
Among 1698 cases with acute MI, 95 had MINOCA (5.6%). MINOCA patients were younger, more often had NSTEMI, lower peak cardiac troponin (cTn) values, and greater ejection fraction than MICAD patients (all P-values <0.005). At hospital discharge, 30-day re-admission rates were similar. MINOCA patients less frequently received optimal medical therapy. When women were analyzed, the 45 women with MINOCA had smaller MIs (P < 0.001) and greater ejection fraction (P = 0.002) than the 358 women with MICAD. Sex comparisons of the 95 MINOCA patients revealed women were older than men (P < 0.001), had lower mean peak cTn values (P < 0.001), greater ejection fraction (P = 0.02), and more single-vessel disease involvement than men (P < 0.0001).
The average MI size is smaller in MINOCA than MICAD patients, and there are sex-related differences in clinical presentation, coronary artery disease extent, and MI size. Re-admission rates are similar and MINOCA patients are less likely to receive guideline recommended medical therapy at discharge.
Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most ...common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined.
The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters.
This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters.
Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684).
In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches ISCHEMIA; NCT01471522)
Display omitted
To evaluate the cardiovascular (CV) prognostic value of adipokines in a large prospective cohort of patients participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.
...The effects of the adipokine levels at baseline and change from baseline on the composite outcome (CV death, myocardial infarction, and stroke) were analyzed using unadjusted and fully adjusted Cox models in 2330 patients with type 2 diabetes and coronary artery disease who had participated in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (from January 1, 2001, through December 1, 2008).
In a fully adjusted model, baseline leptin and change from baseline leptin were protective for CV events, whereas baseline adiponectin, baseline tumor necrosis factor α (TNF-α), change from baseline TNF-α, baseline C-reactive protein (CRP), and change from baseline CRP were harmful. The effect of baseline leptin on CV events depended on the body mass index (BMI), such that the hazard ratios (HRs) varied between 0.6 and 1.4 across the BMI quintiles (interaction P=.03). The same was true for baseline adiponectin (HR varied from 0.7 to 1.7; interaction P=.01), change from baseline monocyte chemoattractant protein-1 (HR varied from 0.8 to 1.8; interaction P=.03), change from baseline TNF-α (HR varied from 0.9 to 1.4; interaction P=.02), and change from baseline IL-6 (HR varied from 0.7 to 1.8; interaction P=.005).
Adipokines are independent predictors of CV events in patients with type 2 diabetes and coronary artery disease. The association between the specific adipokines and CV outcome varies depending on BMI. This reflects the complex pathophysiology of CV disease in obesity and may help explain the "obesity paradox."
clinicaltrials.gov Identifier: NCT00006305.
While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ...ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.
To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.
This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.
CCTA and angina assessment.
Sex differences in stress test, CCTA findings, and symptom severity.
Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 34.4% vs 378 of 3353 11.3%). Of individuals who were randomized, women had more angina at baseline than men (median interquartile range Seattle Angina Questionnaire Angina Frequency score: 80 70-100 vs 90 70-100). Women had less severe ischemia on stress imaging (383 of 919 41.7% vs 1361 of 2972 45.9% with severe ischemia; 386 of 919 42.0% vs 1215 of 2972 40.9% with moderate ischemia; and 150 of 919 16.4% vs 394 of 2972 13.3% with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women 36% vs 1142 of 2418 men 47% with 3-vessel disease; 184 of 568 women 32% vs 754 of 2418 men 31% with 2-vessel disease; and 178 of 568 women 31% vs 519 of 2418 men 22% with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).
Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.
ClinicalTrials.gov Identifier: NCT01471522.
Objectives To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable ...coronary artery disease. Background A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex. Methods We analyzed outcomes in 338 women (15%) and 1949 men (85%) randomized to PCI plus OMT versus OMT alone after adjustment for relevant baseline characteristics. Results There was no difference in treatment effect by sex for the primary end point (death or myocardial infarction; HR, 0.89; 95% CI, 0.77-1.03 for women and HR, 1.02, 95% CI 0.96-1.10 for men; P for interaction = .07). Although the event rate was low, a trend for interaction by sex was nonetheless noted for hospitalization for heart failure, with only women, but not men, assigned to PCI experiencing significantly fewer events as compared to their counterparts receiving OMT alone (HR, 0.59; 95% CI, 0.40-0.84, P < .001 for women and HR, 0.86; 95% CI, 0.74-1.01, P = .47 for men; P for interaction = .02). Both sexes randomized to PCI experienced significantly reduced need for subsequent revascularization (HR, 0.72; 95% CI, 0.62-0.83, P < .001 for women; HR, 0.84; 95% CI, 0.79-0.89, P < .001 for men; P for interaction = .02) with evidence of a sex-based differential treatment effect. Conclusion In this adjusted analysis of the COURAGE trial, there were no significant differences in treatment effect on major outcomes between men and women. However, women assigned to PCI demonstrated a greater benefit as compared to men, with a reduction in heart failure hospitalization and need for future revascularization. These exploratory observations require further prospective study.
The primary objective of the Monotherapy Assessment of Ranolazine In Stable Angina (MARISA) trial was to determine the dose-response relationship of ranolazine, a potentially new anti-anginal ...compound, on symptom-limited exercise duration.
Fatty acids rise precipitously in response to stress, including acute myocardial ischemia. Ranolazine is believed to partially inhibit fatty acid oxidation, shift metabolism toward carbohydrate oxidation, and increase the efficiency of oxygen use.
Patients (n = 191) with angina-limited exercise discontinued anti-anginal medications and were randomized into a double-blind four-period crossover study of sustained-release ranolazine 500, 1,000, or 1,500 mg, or placebo, each administered twice daily for one week. Exercise testing was performed at the end of each treatment during both trough and peak ranolazine plasma concentrations.
Exercise duration at trough increased with ranolazine 500, 1,000, and 1,500 mg twice daily by 94, 103, and 116 s, respectively, all greater (p < 0.005) than the 70-s increase on placebo. Dose-related increases in exercise duration at peak and in times to 1 mm ST-segment depression at trough and peak and to angina at trough and peak were also demonstrated (all p < 0.005). Ranolazine had negligible effects on heart rate and blood pressure. One year survival rate combining data from the MARISA trial and its open-label follow-on study was 96.3 ± 1.7%.
In chronic angina patients, ranolazine monotherapy was well tolerated and increased exercise performance throughout its dosing interval at all doses studied without clinically meaningful hemodynamic effects. One-year survival was not lower than expected in this high-risk patient population. This metabolic approach to treating myocardial ischemia may offer a new therapeutic option for chronic angina patients.
PDF
