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Objective: To examine prevalence and characteristics of newly diagnosed diabetes (NDD) in younger adults hospitalised with acute myocardial infarction (AMI) and investigate whether NDD is associated with health status and clinical outcomes over 12-month post-AMI., Methods: In individuals (18-55 years) admitted with AMI, without established diabetes, we defined NDD as (1) baseline or 1-month HbA1c≥6.5%; (2) discharge diabetes diagnosis or (3) diabetes medication initiation within 1 month. We compared baseline characteristics of NDD, established diabetes and no diabetes, and their associations with baseline, 1-month and 12-month health status (angina-specific and non-disease specific), mortality and in-hospital complications., Results: Among 3501 patients in Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study, 14.5% met NDD criteria. Among 508 patients with NDD, 35 (6.9%) received discharge diagnosis, 91 (17.9%) received discharge diabetes education and 14 (2.8%) initiated pharmacological treatment within 1 month. NDD was more common in non-White (OR 1.58, 95% CI 1.23 to 2.03), obese (OR 1.72, 95% CI 1.39 to 2.12), financially stressed patients (OR 1.27, 95% CI 1.02 to 1.58). Compared with established diabetes, NDD was independently associated with better disease-specific health status and quality of life (p≤0.04). No significant differences were found in unadjusted in-hospital mortality and complications between NDD and established or no diabetes., Conclusions: NDD was common among adults≤55 years admitted with AMI and was more frequent in non-White, obese, financially stressed individuals. Under 20% of patients with NDD received discharge diagnosis or initiated discharge diabetes education or pharmacological treatment within 1 month post-AMI. NDD was not associated with increased risk of worse short-term health status compared with risk noted for established diabetes., Trial Registration Number: NCT00597922., Competing Interests: Competing interests: HK, ES and KJL work under contract with the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. In the past three years, HK received expenses and/or personal fees from UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and Hugo Health, and had grants and/or contracts from the Centers for Medicare & Medicaid Services, Medtronic, the U.S. Food and Drug Administration, Johnson & Johnson, and the Shenzhen Center for Health Information. HB receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799), Astra-Zeneca, BMS, Janssen and Novartis; has received consulting fees from Astra-Zeneca, Bayer, BMS-Pfizer, Novartis and speaking fees or support for attending scientific meetings from Astra-Zeneca, Bayer, BMS-Pfizer, Novartis and MEDSCAPE-the heart.org. JAS is supported by grants from Bayer, serves as a consultant for Janssen, Bayer, Novartis, AstraZeneca and holds the copyright for the Seattle Angina Questionnaire with royalties paid. KJL is also supported by the National Institute on Aging and the American Federation of Aging Research through the Paul Beeson Career Development Award (K23AG04835)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The diagnosis of acute myocardial infarction (AMI) is missed more frequently in young women than men, which may be related to the cognitive psychology of the diagnostic process. Physicians start the diagnostic process by intuitively recognizing familiar symptom phenotypes, but little is known about how symptoms combine in individuals as unique symptom phenotypes. We examined how symptoms of AMI combine as unique symptom phenotypes in individual patients to compare the distribution of symptom phenotypes in women versus men., Methods and Results: The VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) was a multicenter, observational cohort study of 3501 young adults hospitalized with AMI. Data were collected on presenting symptoms with standardized interviews and from medical record abstraction. The number and distribution of unique symptom phenotypes were compared between women and men. Because of the 2:1 female-to-male enrollment ratio, women and men were compared with permutation testing and repeated subsampling. There were 426 interview-symptom phenotypes in women and 280 in men. The observed difference between women and men of 146 phenotypes was significant, even allowing for the greater enrollment of women (permutation P =0.004, median difference 110 under the null hypothesis of no association between sex and phenotype). The repeated subsample analysis also showed significantly more interview-symptom phenotypes in women than men (206.8±7.3 versus 188.6±6.0, P <0.001). Women were more broadly distributed among symptom phenotype subgroups than men ( P <0.001). Similar findings were observed in the analysis of symptoms abstracted from the medical record., Conclusions: Women exhibited substantially more variation in unique symptom phenotypes than men, regardless of whether the symptoms were derived from structured interviews or abstracted from the medical record. These findings may provide an explanation for the higher missed diagnosis rate in young women with AMI and may have important implications for teaching and improving clinicians' ability to recognize the diagnosis of AMI in women.

Background Diabetes mellitus increases the risk of mortality after acute myocardial infarction (AMI). However, little is known about the association of diabetes mellitus with post-AMI health status outcomes (symptoms, functioning, and quality of life) in younger adults. Methods and Results We investigated the association between diabetes mellitus and health status during the first 12 months after AMI, using data from 3501 adults with AMI (42.6% with diabetes mellitus) aged 18 to 55 years enrolled in the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study. Health status was measured with Seattle Angina Questionnaire (SAQ), 12-item Short-Form Health Survey, and EuroQol-Visual Analogue Scale at baseline hospitalization, 1-month, and 12-months post-AMI. At baseline, patients with diabetes mellitus had significantly worse SAQ-angina frequency (81±22 versus 86±19), SAQ-physical limitations (77±28 versus 85±23), SAQ-quality of life (55±25 versus 57±23), 12-item Short-Form Health Survey mental (44±13 versus 46±12)/physical functioning (41±12 versus 46±12), and EuroQol-Visual Analogue Scale (61±22 versus 66±21) than those without diabetes mellitus. Over time, both groups (with and without diabetes mellitus) improved considerably and the differences in health status scores progressively narrowed (except for 12-item Short-Form Health Survey physical functioning). In the linear-mixed effects models, adjusted for sociodemographics, cardiovascular risk factors, comorbidities, clinical characteristics, psychosocial factors, healthcare use, and AMI treatment, diabetes mellitus was associated with worse health status at baseline but not after discharge, and the association did not vary by sex. Conclusions At baseline, young adults with diabetes mellitus had poorer health status than those without diabetes mellitus. After AMI, however, they experienced significant improvements and diabetes mellitus was not associated with worse angina, SAQ-physical limitations, mental functioning, and quality of life, after adjustment for baseline covariates. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00597922.

Background: Young women (aged ≤55 years) with acute myocardial infarction (AMI) have poorer health status outcomes than similarly aged men. Low omega-3 fatty acids (FAs) have been implicated as risk factors for cardiovascular outcomes in AMI patients, but it is not clear whether young women have similar or different post-AMI omega-3 FA profiles compared with young men., Methods and Results: We assessed the sex differences in post-AMI omega-3 FAs and the associations of these biomarkers with patient-reported outcomes (symptom, functioning status, and quality of life) at 12-month follow-up, using data from 2985 US adults with AMI aged 18 to 55 years enrolled in the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) study. Biomarkers including eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid (AA), eicosapentaenoic acid/AA ratio, omega-3/omega-6 ratio, and omega-3 index were measured 1 month after AMI. Overall, the omega-3 FAs and AA were similar in young men and women with AMI. In both unadjusted and adjusted analysis (controlling for age, sex, race, smoking, hypertension, diabetes mellitus, body mass index, and health status score at 1 month), omega-3 FAs and AA were not significantly associated with 12-month health status scores using the Bonferroni corrected statistical threshold., Conclusions: We found no evidence of sex differences in omega-3 FAs and AA in young men and women 1 month after AMI. Omega-3 FAs and AA at 1-month after AMI were generally not associated with 12-month patient-reported health status after adjusting for patient demographic, clinical characteristics, and the corresponding 1-month health status score., (© 2018 The Authors and Quest Diagnostics Inc. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Young women with ST-segment-elevation myocardial infarction experience reperfusion delays more frequently than men. Our aim was to determine the electrocardiographic correlates of delay in reperfusion in young patients with ST-segment-elevation myocardial infarction., Methods and Results: We examined sex differences in initial electrocardiographic characteristics among 1359 patients with ST-segment-elevation myocardial infarction in a prospective, observational, cohort study (2008-2012) of 3501 patients with acute myocardial infarction, 18 to 55 years of age, as part of the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study at 103 US and 24 Spanish hospitals enrolling in a 2:1 ratio for women/men. We created a multivariable logistic regression model to assess the relationship between reperfusion delay (door-to-balloon time >90 or >120 minutes for transfer or door-to-needle time >30 minutes) and electrocardiographic characteristics, adjusting for sex, sociodemographic characteristics, and clinical characteristics at presentation. In our study (834 women and 525 men), women were more likely to exceed reperfusion time guidelines than men (42.4% versus 31.5%; P <0.01). In multivariable analyses, female sex persisted as an important factor in exceeding reperfusion guidelines after adjusting for electrocardiographic characteristics (odds ratio, 1.57; 95% CI, 1.15-2.15). Positive voltage criteria for left ventricular hypertrophy and absence of a prehospital ECG were positive predictors of reperfusion delay; and ST elevation in lateral leads was an inverse predictor of reperfusion delay., Conclusions: Sex disparities in timeliness to reperfusion in young patients with ST-segment-elevation myocardial infarction persisted, despite adjusting for initial electrocardiographic characteristics. Left ventricular hypertrophy by voltage criteria and absence of prehospital ECG are strongly positively correlated and ST elevation in lateral leads is negatively correlated with reperfusion delay., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Young women with acute myocardial infarction (AMI) have a worse prognosis than their male counterparts. We searched for differences in the electrocardiographic presentation of men and women in a large, contemporary registry of young adults with AMI that could help explain gender differences in outcomes. The qualifying electrocardiogram was blindly assessed by a central core lab in 3,354 patients (67% women) aged 18 to 55 years included in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study. Compared with men, women did not have a different frequency of sinus rhythm, and they had shorter PR and QRS intervals and longer QTc intervals. Intraventricular conduction disturbances were not different among genders. Notably, women were more likely than men to have abnormal Q waves in anterior leads and a lower frequency of Q waves in other territories. ST-segment elevation myocardial infarction (STEMI) diagnosis was less frequent in women than in men (44.6% vs 55.1%, p < 0.001). Among patients with STEMI, women had less magnitude and extent of ST-segment elevation than men. In patients with non-STEMI, the frequency, magnitude, and extent of ST-segment depression were not different among genders, but women had anterior ST-segment depression less frequently and anterior negative T waves more frequently compared with men. These differences remained statistically significant after adjusting for baseline characteristics. In conclusion, there are significant gender differences in the electrocardiographic presentation of AMI among young patients. Further studies are warranted to evaluate their impact on gender-related differences in the management and outcomes of AMI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Depression was recently recognized as a risk factor for adverse medical outcomes in patients with acute myocardial infarction (AMI). The degree to which depression is present among younger patients with an AMI, the patient profile associated with being a young AMI patient with depressive symptoms, and whether relevant sex differences exist are currently unknown., Methods and Results: The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study enrolled 3572 patients with AMI (67.1% women; 2:1 ratio for women to men) between 2008 and 2012 (at 103 hospitals in the United States, 24 in Spain, and 3 in Australia). Information about lifetime history of depression and depressive symptoms experienced over the past 2 weeks (Patient Health Questionnaire; a cutoff score ≥10 was used for depression screening) was collected during index AMI admission. Information on demographics, socioeconomic status, cardiovascular risk, AMI severity, perceived stress (14-item Perceived Stress Scale), and health status (Seattle Angina Questionnaire, EuroQoL 5D) was obtained through interviews and chart abstraction. Nearly half (48%) of the women reported a lifetime history of depression versus 1 in 4 in men (24%; P<0.0001). At the time of admission for AMI, more women than men experienced depressive symptoms (39% versus 22%, P<0.0001; adjusted odds ratio 1.64; 95% CI 1.36 to 1.98). Patients with more depressive symptoms had higher levels of stress and worse quality of life (P<0.001). Depressive symptoms were more prevalent among patients with lower socioeconomic profiles (eg, lower education, uninsured) and with more cardiovascular risk factors (eg, diabetes, smoking)., Conclusions: A high rate of lifetime history of depression and depressive symptoms at the time of an AMI was observed among younger women compared with men. Depressive symptoms affected those with more vulnerable socioeconomic and clinical profiles., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)