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As the population ages, the global cardiovascular disease burden will continue to increase, particularly among older adults. Increases in life expectancy and better cardiovascular care have significantly reshaped the epidemiology of cardiovascular disease and have created new patient profiles. The combination of older age, multiple comorbidities, polypharmacy, frailty, and adverse noncardiovascular outcomes is challenging our routine clinical practice in this field. In this review, we examine noncardiovascular factors that statistically interact in a relevant way with health status and quality of life in older people with cardiovascular disease. We focused on specific geriatric conditions (multimorbidity, polypharmacy, geriatric syndromes, and frailty) that are responsible for a major risk of functional decline and have an important impact on the overall prognosis in this patient population.

Background: In patients with ST-segment–elevation myocardial infarction and multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions guided by fractional flow reserve (FFR) is superior to treatment of the culprit lesion alone. Whether deferring nonculprit PCI is safe in this specific context is questionable. We aimed to assess clinical outcomes at 1 year in ST-segment–elevation myocardial infarction patients with multivessel coronary artery disease and an FFR-guided strategy for nonculprit lesions, according to whether or not ≥1 PCI was performed. Methods: Outcomes were analyzed in patients of the randomized FLOWER-MI (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) trial in whom, after successful primary PCI, nonculprit lesions were assessed using FFR. The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and unplanned hospitalization with urgent revascularization at 1 year. Results: Among 1171 patients enrolled in this study, 586 were assigned to the FFR-guided group: 388 (66%) of them had ≥1 PCI, and 198 (34%) had no PCI. Mean FFR before decision (ie, PCI or not) of nonculprit lesions was 0.75±0.10 and 0.88±0.06, respectively. During follow-up, a primary outcome event occurred in 16 of 388 patients (4.1%) in patients with PCI and in 16 of 198 patients (8.1%) in patients without PCI (adjusted hazard ratio, 0.42 [95% CI, 0.20–0.88]; P =0.02). Conclusions: In patients with ST-segment–elevation myocardial infarction undergoing complete revascularization guided by FFR measurement, those with ≥1 PCI had lower event rates at 1 year, compared with patients with deferred PCI, suggesting that deferring lesions judged relevant by visual estimation but with FFR >0.80 may not be optimal in this context. Future randomized studies are needed to confirm these data. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02943954. Graphic Abstract: A graphic abstract is available for this article.

Data are inconsistent regarding sex-differences in the relative rates of cardiovascular events associated with diabetes. We aimed to investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age. Methods: All patients seen in French hospitals in 2013 with at least 5 years or follow-up (or dying earlier) without a history major adverse cardiovascular event, were identified and characterized by individual-level linkage of French nationwide administrative registers. They were categorized by diabetes-status and followed-up until 31 December 2019. Using Cox models, we calculated overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischemic stroke, or cardiovascular death (MACE-HF). Results: The study included 3,381,472 individuals among whom 482,848 (14.3%) had diabetes (88.1% with type 2 diabetes). Among 482,848 (45% women) patients with diabetes, the absolute rate of MACE-HF was higher in men than in women (9.7 vs. 7.4 per 100 person-years). Corresponding absolute rates in men and women without diabetes were 4.9 vs. 3.1 per 100 person-years. Comparing individuals with and without diabetes, women had higher incidence rate ratio (IRR) of MACE-HF than men (IRR 2.42 95% confidence interval [CI] 2.40-2.44) in women vs. 1.99, 95% CI 1.98-2.01 in men) with a women-to-men ratio (WMR) of 1.22 (CI 1.20-1.23, p Conclusion: Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in recent years.

BACKGROUND Dual antiplatelet therapy (DAPT) associating aspirin + clopidogrel is commonly utilized in neurovascular interventions despite unpredictable clopidogrel efficacy with 4% to 50% of patients considered nonresponders. Ticagrelor is an antiplatelet agent with low resistance rates but unknown efficacy and safety in neurovascular patients. OBJECTIVE To evaluate frequency of ischemic and hemorrhagic events in patients treated with aspirin and ticagrelor when associated with perioperative heparin bolus for unruptured aneurysms treated with intracranial stents. METHODS One hundred fifty-four consecutive patients with unruptured intracranial aneurysms treated by stent procedures (113 = flow diverter stent [FDS], 41 = stent-assisted coiling) were retrospectively analyzed. All patients received aspirin and ticagrelor without platelet function testing. Patients were separated in 2 groups following perioperative heparin dose: group I = 70 U/kg; group II = 50 U/kg. FDS versus stent-assisted coiling procedures were also separately analyzed. RESULTS Nine patients (5.8%) presented symptomatic neurological complications poststenting (3 ischemic, 6 hemorrhagic): 8 patients received 70 U/kg of heparin (11.1%) and 1 patient received 50 U/kg (1.2%; P

Background— Pharmacological inhibition of cyclooxygenase-2 increases the risk of myocardial infarction (MI) and stroke. Microsomal prostaglandin (PG) E 2 synthase-1 (mPGES-1), encoded by the Ptges gene, functions downstream from cyclooxygenase-2 in the inducible PGE 2 biosynthetic pathway. We caused acute MI in Ptges +/+ and Ptges −/− mice to define the role of mPGES-1 in cardiac ischemic injury. Methods and Results— Twenty-eight days after MI, Ptges −/− mice develop more left ventricular (LV) dilation, have worse LV systolic and diastolic function, and have higher LV end-diastolic pressure than Ptges +/+ mice but have similar pulmonary wet-to-dry weight ratios, cardiac mass, infarct size, and mortality. The length-to-width ratio of individual cardiomyocytes is significantly greater in Ptges −/− than Ptges +/+ mice after MI, a finding consistent with eccentric cardiomyocyte hypertrophy in Ptges −/− mice. Expression of atrial natriuretic peptide, brain natriuretic peptide, and α- and β-myosin heavy chain, markers of ventricular hypertrophy, is higher in the LV of Ptges −/− than Ptges +/+ mice after MI. Ptges +/+ mice express cyclooxygenase-2 and mPGES-1 protein in inflammatory cells adjacent to the infarct after MI but do not express these proteins in cardiomyocytes. Ptges −/− mice express cyclooxygenase-2 in inflammatory cells adjacent to the infarct and do not express mPGES-1 in any cells in the heart. Levels of PGE 2 but not PGD 2 , thromboxane A 2 , PGI 2 , or PGF 2α are higher in the infarct and LV remote from the infarct after MI in Ptges +/+ than Ptges −/− mice. Conclusions— In Ptges +/+ mice, mPGES-1 in inflammatory cells catalyzes PGE 2 biosynthesis in the LV after MI. Deletion of mPGES-1 leads to eccentric cardiac myocyte hypertrophy, LV dilation, and impaired LV contractile function after acute MI.

Background— We previously demonstrated that ischemic postconditioning decreases creatine kinase release, a surrogate marker for infarct size, in patients with acute myocardial infarction. Our objective was to determine whether ischemic postconditioning could afford (1) a persistent infarct size limitation and (2) an improved recovery of myocardial contractile function several months after infarction. Methods and Results— Patients presenting within 6 hours of the onset of chest pain, with suspicion for a first ST-segment–elevation myocardial infarction, and for whom the clinical decision was made to treat with percutaneous coronary intervention, were eligible for enrollment. After reperfusion by direct stenting, 38 patients were randomly assigned to a control (no intervention; n=21) or postconditioned group (repeated inflation and deflation of the angioplasty balloon; n=17). Infarct size was assessed both by cardiac enzyme release during early reperfusion and by 201 thallium single photon emission computed tomography at 6 months after acute myocardial infarction. At 1 year, global and regional contractile function was evaluated by echocardiography. At 6 months after acute myocardial infarction, single photon emission computed tomography rest-redistribution index (a surrogate for infarct size) averaged 11.8±10.3% versus 19.5±13.3% in the postconditioned versus control group ( P =0.04), in agreement with the significant reduction in creatine kinase and troponin I release observed in the postconditioned versus control group (−40% and −47%, respectively). At 1 year, the postconditioned group exhibited a 7% increase in left ventricular ejection fraction compared with control ( P =0.04). Conclusions— Postconditioning affords persistent infarct size reduction and improves long-term functional recovery in patients with acute myocardial infarction.

Introduction. mPGES functions downstream from COX-2 in the inducible PGE 2 biosynthetic pathway, and can be expressed by cardiac myocytes and inflammatory cells. mPGES gene targeted mice (mPGES −/− ) develop LV dilation and impaired contractile function after MI. The purpose of this study was to determine if mPGES in bone marrow (BM) derived inflammatory cells regulates LV remodelling after MI. Methods. Six week old female mPGES +/+ mice were irradiated with 9.5 Gy and transplanted with BM from male mPGES +/+ or mPGES −/− mice (BM +/+ or BM −/− chimeras, respectively). After 10 weeks, the left coronary artery was ligated. Echocardiography was used to assess LV dimensions and function in vivo . After fixation in situ , LV dimensions and infarct volume was assessed by planimetry. The efficiency of BM transplantation, determined by the ratio of syr to gapdh DNA, measured by real time PCR, was 98%. Results. There was no difference in LV dimensions or function between BM +/+ and BM −/− mice before MI (not shown). Between 7 and 28 days post MI, ejection fraction did not change in BM +/+ mice, but decreased significantly in BM −/− mice (Table ). BM −/− mice also had a higher LV diameter (2.7 ± 0.1 vs. 3.1 ± 0.1 mm, p = 0.0001) and LV volume (14 ± 0.8 vs. 18 ± 1.0 mm 3 , p = 0.025) than BM +/+ mice 28 days after MI. In contrast, there was no difference in the percentage of infarcted LV, heart rate or cardiac output between BM +/+ and BM −/− mice after MI. Survival of BM +/+ vs. BM −/− 28 days after MI was similar (75% vs. 72%, log rank, p = 0.86). Conclusion. mPGES1 in bone marrow cells that localize to the heart after MI is necessary to maintain post infarction LV contractile function, and to prevent adverse LV remodelling. Use of mPGES inhibitors as substitutes for COX-2 inhibitors may be detrimental in patients with coronary artery disease.

Background— Cell transplantation offers the promise in the restoration of ventricular function after an extensive myocardial infarction, but the optimal cell type remains controversial. Human unrestricted somatic stem cells (USSCs) isolated from umbilical cord blood have great potential to differentiate into myogenic cells and induce angiogenesis. The present study evaluated the effect of USSCs on myocardial regeneration and improvement of heart function after myocardial infarction in a porcine model. Method and Results— The distal left anterior descending artery of Yorkshire pigs (30 to 35 kg) was occluded by endovascular implantation of a coil. Four weeks after infarction, single-photon emission computed tomography technetium 99m sestamibi scans (MIBI) and echocardiography were performed. USSCs (100×10 6 ) or culture media were then directly injected into the infarcted region (n=8 per group). Pigs were immunosuppressed by daily administration of cyclosporin A. At 4 weeks after transplantation, MIBI and echocardiography were repeated and heart function was also assessed with a pressure-volume catheter. The infarcted myocardium and implanted cells were studied histologically. MIBI showed improved regional perfusion ( P P P Conclusion— Engrafted USSCs were detected in the infarct region 4 weeks after cell transplantation, and the implanted cells improved regional and global function of the porcine heart after a myocardial infarction. This study suggests that the USSC implantation will be efficacious for cellular cardiomyoplasty.