Sex differences in body composition in people with prediabetes and type 2 diabetes as compared with people with normal glucose metabolism: the Maastricht Study

Aims/hypothesis: Obesity is a major risk factor for type 2 diabetes. However, body composition differs between women and men. In this study we investigate the association between diabetes status and body composition and whether this association is moderated by sex. Methods: In a population-based cohort study (n=7639; age 40–75 years, 50% women, 25% type 2 diabetes), we estimated the sex-specific associations, and differences therein, of prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes (reference: normal glucose metabolism [NGM]) with dual-energy x-ray absorptiometry (DEXA)- and MRI-derived measures of body composition and with hip circumference. Sex differences were analysed using adjusted regression models with interaction terms of sex-by-diabetes status. Results: Compared with their NGM counterparts, both women and men with prediabetes and type 2 diabetes had more fat and lean mass and a greater hip circumference. The differences in subcutaneous adipose tissue, hip circumference and total and peripheral lean mass between type 2 diabetes and NGM were greater in women than men (women minus men [W–M] mean difference [95% CI]: 15.0 cm2 [1.5, 28.5], 3.2 cm [2.2, 4.1], 690 g [8, 1372] and 443 g [142, 744], respectively). The difference in visceral adipose tissue between type 2 diabetes and NGM was greater in men than women (W–M mean difference [95% CI]: −14.8 cm2 [−26.4, −3.1]). There was no sex difference in the percentage of liver fat between type 2 diabetes and NGM. The differences in measures of body composition between prediabetes and NGM were generally in the same direction, but were not significantly different between women and men. Conclusions/interpretation: This study indicates that there are sex differences in body composition associated with type 2 diabetes. The pathophysiological significance of these sex-associated differences requires further study. Graphical abstract: [Figure not available: see fulltext.]

Real-World Implementation of a Genotype-Guided P2Y12 Inhibitor De-Escalation Strategy in Acute Coronary Syndrome Patients

Background: CYP2C19 genotype–guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). Objectives: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. Methods: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year. Results: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76). Conclusions: The implementation of a CYP2C19 genotype–guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen

Rationale and design of the future optimal research and care evaluation in patients with acute coronary syndrome (Force-acs) registry: Towards “personalized medicine” in daily clinical practice

Diagnostic and treatment strategies for acute coronary syndrome have improved dramatically over the past few decades, but mortality and recurrent myocardial infarction rates remain high. An aging population with increasing co-morbidities heralds new clinical challenges. Therefore, in order to evaluate and improve current treatment strategies, detailed information on clinical presentation, treatment and follow-up in real-world patients is needed. The Future Optimal Research and Care Evaluation in patients with Acute Coronary Syndrome (FORCE-ACS) registry (ClinicalTrials.gov Identifier: NCT03823547) is a multi-center, prospective real-world registry of patients admitted with (suspected) acute coronary syndrome. Both non-interventional and interventional cardiac centers in different regions of the Netherlands are currently participating. Patients are treated according to local protocols, enabling the evaluation of different diagnostic and treatment strategies used in daily practice. Data collection is performed using electronic medical records and quality-of-life questionnaires, which are sent 1, 12, 24 and 36 months after initial admission. Major end points are all-cause mortality, myocardial infarction, stent thrombosis, stroke, revascularization and all bleeding requiring medical attention. Invasive therapy, antithrombotic therapy including patient-tailored strategies, such as the use of risk scores, pharmacogenetic guided antiplatelet therapy and patient reported outcome measures are monitored. The FORCE-ACS registry provides insight into numerous aspects of the (quality of) care for acute coronary syndrome patients

Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients:Rationale and design of the LEGACY study

Background: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. Methods: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. Conclusions: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS