Changes in opioid prescribing in veterans with headache during the COVID-19 pandemic: A regression discontinuity in time analysis.

OBJECTIVE: To determine changes in opioid prescribing among veterans with headaches during the coronavirus disease of 2019 (COVID-19) pandemic by comparing the stay-at-home phase (March 15 to May 30, 2020) and the reopening phase (May 31 to December 31, 2020). BACKGROUND: Opioid prescribing for chronic pain has declined substantially since 2016; however, changes in opioid prescribing during the COVID-19 pandemic among veterans with headaches remain unknown. METHODS: This retrospective cohort study utilized regression discontinuity in time and difference-in-differences design to analyze veterans aged ≥18 years with a previous diagnosis of headache disorders and an outpatient visit to the Veterans Health Administration (VHA) during the study period. We measured the weekly number of opioid prescriptions, the number of days supplied, the daily dose in morphine milligram equivalents (MMEs), and the number of prescriptions with ≥50 morphine equivalent daily doses (MEDD). RESULTS: A total of 81,376 veterans were analyzed with 589,950 opioid prescriptions. The mean (SD) age was 51.6 (13.5) years, 57,242 (70.3%) were male, and 53,464 (65.7%) were White. During the pre-pandemic period, 323.6 opioid prescriptions (interquartile range 292.1-325.8) were dispensed weekly, with an median (IQR) of 24.1 (24.0-24.4) days supplied and 31.8 (31.2-32.5) MMEs. Transition to stay-at-home was associated with a 7.7% decrease in the number of prescriptions (incidence rate ratio [IRR] 1.077, 95% confidence interval [CI] 0.866-0.984) and a 9.8% increase in days supplied (IRR 1.098, 95% CI 1.078-1.119). Similar trends were observed during the reopening period. Subgroup analysis among veterans on long-term opioid therapy also revealed 1.7% and 1.4% increases in days supplied during the stay-at-home (IRR 1.017, 95% CI 1.009-1.025) and reopening phase (IRR 1.014, 95% CI 1.007-1.021); however, changes in the total number of prescriptions, MME/day, or the number of prescriptions >50 MEDD were insignificant. CONCLUSION: Prescription opioid access was maintained for veterans within VHA during the pandemic. The de-escalation of opioid prescribing observed prior to the pandemic was not seen in our study.

Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients).

BACKGROUND: Some studies report that women are less likely to present with chest pain for acute myocardial infarction (AMI). Information on symptom presentation, perception of symptoms, and care-seeking behaviors is limited for young patients with AMI. METHODS: We interviewed 2009 women and 976 men aged 18 to 55 years hospitalized for AMI at 103 US hospitals participating in the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Structured patient interviews during the index AMI hospitalization were used to collect information on symptom presentation, perception of symptoms, and care-seeking behaviors. We compared patient characteristics and presentation information by sex. Multivariable hierarchical logistic regression was used to evaluate the association between sex and symptom presentation. RESULTS: The majority of women (87.0%) and men (89.5%) presented with chest pain (defined as pain, pressure, tightness, or discomfort). Women were more likely to present with ≥3 associated symptoms than men (eg, epigastric symptoms, palpitations, and pain or discomfort in the jaw, neck, arms, or between the shoulder blades; 61.9% for women versus 54.8% for men, P<0.001). In adjusted analyses, women with an ST-segment-elevation AMI were more likely than men to present without chest pain (odds ratio, 1.51; 95% confidence interval, 1.03-2.22). In comparison with men, women were more likely to perceive symptoms as stress/anxiety (20.9% versus 11.8%, P<0.001) but less likely to attribute symptoms to muscle pain (15.4% versus 21.2%, P=0.029). Approximately 29.5% of women and 22.1% of men sought medical care for similar symptoms before their hospitalization (P<0.001); however, 53% of women reported that their provider did not think these symptoms were heart-related in comparison with 37% of men (P<0.001). CONCLUSIONS: The presentation of AMI symptoms was similar for young women and men, with chest pain as the predominant symptom for both sexes. Women presented with a greater number of additional non-chest pain symptoms regardless of the presence of chest pain, and both women and their healthcare providers were less likely to attribute their prodromal symptoms to heart disease in comparison with men.

Sex differences in lipid profiles and treatment utilization among young adults with acute myocardial infarction: Results from the VIRGO study.

BACKGROUND: Young women with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. An adverse lipid profile is an important risk factor for cardiovascular outcomes after AMI, but little is known about whether young women with AMI have a higher-risk lipid pattern than men. We characterized sex differences in lipid profiles and treatment utilization among young adults with AMI. METHODS: A total of 2,219 adults with AMI (1,494 women) aged 18-55 years were enrolled from 103 hospitals in the United States (2008-2012). Serum lipids and lipoprotein subclasses were measured 1 month after discharge. RESULTS: More than 90% of adults were discharged on a statin, but less than half received a high-intensity dose and 12% stopped taking treatments by 1 month. For both men and women, the median of low-density lipoprotein (LDL) cholesterol was reduced to <100 mg/dL 1 month after discharge for AMI, but high-density lipoprotein (HDL) cholesterol remained <40 mg/dL. Multivariate regression analyses showed that young women had favorable lipoprotein profiles compared with men: women had higher HDL cholesterol and HDL large particle, but lower total cholesterol-to-HDL cholesterol ratio and LDL small particle. CONCLUSIONS: Young women with AMI had slightly favorable lipid and lipoprotein profiles compared with men, suggesting that difference in lipid and lipoprotein may not be a major contributor to sex differences in outcomes after AMI. In both men and women, statin remained inadequately used, and low HDL cholesterol level was a major lipid abnormality.

Gender differences in the trajectory of recovery in health status among young patients with acute myocardial infarction: results from the variation in recovery: role of gender on outcomes of young AMI patients (VIRGO) study.

BACKGROUND: Despite the excess risk of mortality in young women (≤55 years of age) after acute myocardial infarction (AMI), little is known about young women's health status (symptoms, functioning, quality of life) during the first year of recovery after an AMI. We examined gender differences in health status over time from baseline to 12 months after AMI. METHODS AND RESULTS: A total of 3501 AMI patients (67% women) 18 to 55 years of age were enrolled from 103 US and 24 Spanish hospitals. Data were obtained by medical record abstraction and patient interviews at baseline hospitalization and 1 and 12 months after AMI. Health status was measured by generic (Short Form-12) and disease-specific (Seattle Angina Questionnaire) measures. We compared health status scores at all 3 time points and used longitudinal linear mixed-effects analyses to examine the independent effect of gender, adjusting for time and selected covariates. Women had significantly lower health status scores than men at each assessment (all P values <0.0001). After adjustment for time and all covariates, women had Short Form-12 physical/mental summary scores that were -0.96 (95% confidence interval [CI], -1.59 to -0.32) and -2.36 points (95% CI, -2.99 to -1.73) lower than those of men, as well as worse Seattle Angina Questionnaire physical limitations (-2.44 points lower; 95% CI, -3.53 to -1.34), more angina (-1.03 points lower; 95% CI, -1.98 to -0.07), and poorer quality of life (-3.51 points lower; 95% CI, -4.80 to -2.22). CONCLUSION: Although both genders recover similarly after AMI, women have poorer scores than men on all health status measures, a difference that persisted throughout the entire year after discharge.

Sex differences in perceived stress and early recovery in young and middle-aged patients with acute myocardial infarction.

BACKGROUND: Younger age and female sex are both associated with greater mental stress in the general population, but limited data exist on the status of perceived stress in young and middle-aged patients presenting with acute myocardial infarction. METHODS AND RESULTS: We examined sex difference in stress, contributing factors to this difference, and whether this difference helps explain sex-based disparities in 1-month recovery using data from 3572 patients with acute myocardial infarction (2397 women and 1175 men) 18 to 55 years of age. The average score of the 14-item Perceived Stress Scale at baseline was 23.4 for men and 27.0 for women (P<0.001). Higher stress in women was explained largely by sex differences in comorbidities, physical and mental health status, intrafamily conflict, caregiving demands, and financial hardship. After adjustment for demographic and clinical characteristics, women had worse recovery than men at 1 month after acute myocardial infarction, with mean differences in improvement score between women and men ranging from -0.04 for EuroQol utility index to -3.96 for angina-related quality of life (P<0.05 for all). Further adjustment for baseline stress reduced these sex-based differences in recovery to -0.03 to -3.63, which, however, remained statistically significant (P<0.05 for all). High stress at baseline was associated with significantly worse recovery in angina-specific and overall quality of life, as well as mental health status. The effect of baseline stress on recovery did not vary between men and women. CONCLUSIONS: Among young and middle-aged patients, higher stress at baseline is associated with worse recovery in multiple health outcomes after acute myocardial infarction. Women perceive greater psychological stress than men at baseline, which partially explains women's worse recovery.

Sexual activity and counseling in the first month after acute myocardial infarction among younger adults in the United States and Spain: a prospective, observational study.

BACKGROUND: United States and European cardiovascular society guidelines recommend physicians counsel patients about resuming sexual activity after acute myocardial infarction (AMI), but little is known about patients' experience with counseling about sexual activity after AMI. METHODS AND RESULTS: The prospective, longitudinal Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study, conducted at 127 hospitals in the United States and Spain, was designed, in part, to evaluate gender differences in baseline sexual activity, function, and patient experience with physician counseling about sexual activity after an AMI. This study used baseline and 1-month data collected from the 2:1 sample of women (N=2349) and men (N=1152) ages 18 to 55 years with AMI. Median age was 48 years. Among those who reported discussing sexual activity with a physician in the month after AMI (12% of women, 19% of men), 68% were given restrictions: limit sex (35%), take a more passive role (26%), and/or keep the heart rate down (23%). In risk-adjusted analyses, factors associated with not discussing sexual activity with a physician included female gender (relative risk, 1.07; 95% confidence interval, 1.03-1.11), age (relative risk, 1.05 per 10 years; 95% confidence interval, 1.02-1.08), and sexual inactivity at baseline (relative risk, 1.11; 95% confidence interval, 1.08-1.15). Among patients who received counseling, women in Spain were significantly more likely to be given restrictions than U.S. women (relative risk; 1.36, 95% confidence interval, 1.11-1.66). CONCLUSIONS: Very few patients reported counseling for sexual activity after AMI. Those who did were commonly given restrictions not supported by evidence or guidelines. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00597922.

Design and rationale of the comprehensive evaluation of risk factors in older patients with AMI (SILVER-AMI) study.

BACKGROUND: While older adults (age 75 and over) represent a large and growing proportion of patients with acute myocardial infarction (AMI), they have traditionally been under-represented in cardiovascular studies. Although chronological age confers an increased risk for adverse outcomes, our current understanding of the heterogeneity of this risk is limited. The Comprehensive Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study was designed to address this gap in knowledge by evaluating risk factors (including geriatric impairments, such as muscle weakness and cognitive impairments) for hospital readmission, mortality, and health status decline among older adults hospitalized for AMI. METHODS/DESIGN: SILVER-AMI is a prospective cohort study that is enrolling 3000 older adults hospitalized for AMI from a recruitment network of approximately 70 community and academic hospitals across the United States. Participants undergo a comprehensive in-hospital assessment that includes clinical characteristics, geriatric impairments, and health status measures. Detailed medical record abstraction complements the assessment with diagnostic study results, in-hospital procedures, and medications. Participants are subsequently followed for six months to determine hospital readmission, mortality, and health status decline. Multivariable regression will be used to develop risk models for these three outcomes. DISCUSSION: SILVER-AMI will fill critical gaps in our understanding of AMI in older patients. By incorporating geriatric impairments into our understanding of post-AMI outcomes, we aim to create a more personalized assessment of risk and identify potential targets for interventions. TRIAL REGISTRATION NUMBER: NCT01755052 .

Characteristics and Gender Differences of Headache in the Veterans Health Administration: A National Cohort Study, Fiscal Year 2008-2019.

BACKGROUND AND OBJECTIVES: - To determine gender differences in headache types diagnosed, sociodemographic characteristics, military campaign and exposures, and healthcare utilization among United States (U.S.) Veterans in the Veterans Health Administration (VHA). METHODS: - This study employed a retrospective cohort design to examine VHA Electronic Health Record (EHR) data. This cohort includes Veterans who had at least one visit for any headache between fiscal years 2008 and 2019. Headache diagnoses were classified into eight categories using International Classification of Disease, Clinical Modification codes. Demographics, military-related exposures, comorbidities, and type of provider(s) consulted were extracted from the EHR, and compared by gender. Age-adjusted incidence and prevalence rates of medically diagnosed headache disorders were calculated separately for each type of headache. RESULTS: - Of the 1,524,960 Veterans with headache diagnoses included in the cohort, 82.8% were men. Compared with women, men were more often white (70.4% vs 56.7%), older (52.0±16.8 vs 41.9±13.0 years), with higher rates of traumatic brain injury (2.9% vs 1.1%) and post-traumatic stress disorder (23.7% vs 21.7%), and lower rates of military sexual trauma (3.2% vs 33.7%; p<0.001 for all). Age adjusted incidence rate of headache of any type was higher among women. Migraine and trigeminal autonomic cephalalgias rates were most stable over time. Men were more likely than women to be diagnosed with headache not-otherwise-specified (77.4% vs 67.7%) and have higher incidence rates of headaches related to trauma (3.4% vs 1.9% [post-traumatic]; 5.5% vs 5.1% [post-whiplash]; p <0.001 for all). Men also had fewer headache types diagnosed (mean ± standard deviation; 1.3 ± 0.6 vs 1.5 ± 0.7), had fewer encounters for headache/year (0.8 ± 1.2 vs 1.2 ± 1.6) and fewer visits to headache specialists (20.8% vs 27.4% p <0.001 for all), compared to women. Emergency Department utilization for headache care was high for both genders and higher for women compared to men (20.3% vs 22.9%; p<0.001). DISCUSSION: - Among Veterans with headache diagnoses, important gender differences exist for men and women Veterans receiving headache care within VHA regarding sociodemographic characteristics, headache diagnoses, military exposure, and headache healthcare utilization. The findings have potential implications for providers and the healthcare system caring for Veterans living with headache.

Development and Validation of a Risk Prediction Model for 1-Year Readmission Among Young Adults Hospitalized for Acute Myocardial Infarction.

Background Readmission over the first year following hospitalization for acute myocardial infarction (AMI) is common among younger adults (≤55 years). Our aim was to develop/validate a risk prediction model that considered a broad range of factors for readmission within 1 year. Methods and Results We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which enrolled young adults aged 18 to 55 years hospitalized with AMI across 103 US hospitals (N=2979). The primary outcome was ≥1 all-cause readmissions within 1 year of hospital discharge. Bayesian model averaging was used to select the risk model. The mean age of participants was 47.1 years, 67.4% were women, and 23.2% were Black. Within 1 year of discharge for AMI, 905 (30.4%) of participants were readmitted and were more likely to be female, Black, and nonmarried. The final risk model consisted of 10 predictors: depressive symptoms (odds ratio [OR], 1.03; 95% CI, 1.01-1.05), better physical health (OR, 0.98; 95% CI, 0.97-0.99), in-hospital complication of heart failure (OR, 1.44; 95% CI, 0.99-2.08), chronic obstructive pulmomary disease (OR, 1.29; 95% CI, 0.96-1.74), diabetes mellitus (OR, 1.23; 95% CI, 1.00-1.52), female sex (OR, 1.31; 95% CI, 1.05-1.65), low income (OR, 1.13; 95% CI, 0.89-1.42), prior AMI (OR, 1.47; 95% CI, 1.15-1.87), in-hospital length of stay (OR, 1.13; 95% CI, 1.04-1.23), and being employed (OR, 0.88; 95% CI, 0.69-1.12). The model had excellent calibration and modest discrimination (C statistic=0.67 in development/validation cohorts). Conclusions Women and those with a prior AMI, increased depressive symptoms, longer inpatient length of stay and diabetes may be more likely to be readmitted. Notably, several predictors of readmission were psychosocial characteristics rather than markers of AMI severity. This finding may inform the development of interventions to reduce readmissions in young patients with AMI.

Protocol for serious fall injury adjudication in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study.

BACKGROUND: This paper describes a protocol for determining the incidence of serious fall injuries for Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE), a large, multicenter pragmatic clinical trial with limited resources for event adjudication. We describe how administrative data (from participating health systems and Medicare claims) can be used to confirm participant-reported events, with more time- and resource-intensive full-text medical record data used only on an "as-needed" basis. METHODS: STRIDE is a pragmatic cluster-randomized controlled trial involving 5451 participants age ≥ 70 and at increased risk for falls, served by 86 primary care practices in 10 US health systems. The STRIDE intervention involves a nurse falls care manager who assesses a participant's underlying risks for falls, suggests interventions using motivational interviewing, and then creates, implements and longitudinally follows up on an individualized care plan with the participant (and caregiver when appropriate), in partnership with the participant's primary care provider. STRIDE's primary outcome is serious fall injuries, defined as a fall resulting in: (1) medical attention billable according to Medicare guidelines with a) fracture (excluding isolated thoracic vertebral and/or lumbar vertebral fracture), b) joint dislocation, or c) cut requiring closure; OR (2) overnight hospitalization with a) head injury, b) sprain or strain, c) bruising or swelling, or d) other injury determined to be "serious" (i.e., burn, rhabdomyolysis, or internal injury). Two sources of data are required to confirm a serious fall injury. The primary data source is the participant's self-report of a fall leading to medical attention, identified during telephone interview every 4 months, with the confirmatory source being (1) administrative data capturing encounters at the participating health systems or Medicare claims and/or (2) the full text of medical records requested only as needed. DISCUSSION: Adjudication is ongoing, with over 1000 potentially qualifying events adjudicated to date. Administrative data can be successfully used for adjudication, as part of a hybrid approach that retrieves full-text medical records only when needed. With the continued refinement and availability of administrative data sources, future studies may be able to use administrative data completely in lieu of medical record review to maximize the quality of adjudication with finite resources. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02475850).

Sex Differences in Timeliness of Reperfusion in Young Patients With ST-Segment-Elevation Myocardial Infarction by Initial Electrocardiographic Characteristics.

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.

Sex Differences in Inflammatory Markers and Health Status Among Young Adults With Acute Myocardial Infarction: Results From the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) Study.

BACKGROUND: Young women (≤55 years of age) with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. Elevated inflammatory markers are associated with an increased risk of cardiovascular outcomes after AMI, but little is known about whether young women have higher inflammatory levels after AMI compared with young men. METHODS AND RESULTS: We assessed sex differences in post-AMI inflammatory markers and whether such differences account for sex differences in 12-month health status, using data from 2219 adults with AMI, 18 to 55 years of age, in the United States. Inflammatory markers including high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 were measured 1 month after AMI. Overall, women had higher levels of hsCRP and lipoprotein-associated phospholipase A2 after AMI compared with men, and this remained statistically significant after multivariable adjustment. Regression analyses showed that elevated 1-month hsCRP was associated with poor health status (symptom, function, and quality of life) at 12 months. However, the association between hsCRP and health status became nonsignificant after adjustment for sociodemographics, comorbidities, and treatment factors. Half of these patients had residual inflammatory risk (hsCRP >3 mg/L) compared with a third who had residual cholesterol risk (Low-density lipoprotein cholesterol >100 mg/dL). CONCLUSIONS: Young women with AMI had higher inflammatory levels compared with young men. Elevated 1-month hsCRP was associated with poor health status at 12 months after AMI, but this was attenuated after adjustment for patient characteristics. Targeted anti-inflammatory treatments are worthy of consideration for secondary prevention in these patients if ongoing trials of anti-inflammatory therapy prove effective.

Editor's Choice-Sex differences in young patients with acute myocardial infarction: A VIRGO study analysis.

AIMS: Young women with acute myocardial infarction (AMI) have a higher risk of adverse outcomes than men. However, it is unclear how young women with AMI are different from young men across a spectrum of characteristics. We sought to compare young women and men at the time of AMI on six domains of demographic and clinical factors in order to determine whether they have distinct profiles. METHODS AND RESULTS: Using data from Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO), a prospective cohort study of women and men aged ⩽55 years hospitalized for AMI ( n = 3501) in the United States and Spain, we evaluated sex differences in demographics, healthcare access, cardiovascular risk and psychosocial factors, symptoms and pre-hospital delay, clinical presentation, and hospital management for AMI. The study sample included 2349 (67%) women and 1152 (33%) men with a mean age of 47 years. Young women with AMI had higher rates of cardiovascular risk factors and comorbidities than men, including diabetes, congestive heart failure, chronic obstructive pulmonary disease, renal failure, and morbid obesity. They also exhibited higher levels of depression and stress, poorer physical and mental health status, and lower quality of life at baseline. Women had more delays in presentation and presented with higher clinical risk scores on average than men; however, men presented with higher levels of cardiac biomarkers and more classic electrocardiogram findings. Women were less likely to undergo revascularization procedures during hospitalization, and women with ST segment elevation myocardial infarction were less likely to receive timely primary reperfusion. CONCLUSIONS: Young women with AMI represent a distinct, higher-risk population that is different from young men.

Comparison of Electrocardiographic Characteristics in Men Versus Women ≤ 55 Years With Acute Myocardial Infarction (a Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients Substudy).

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.

Sexual Activity and Function in the Year After an Acute Myocardial Infarction Among Younger Women and Men in the United States and Spain.

Importance: Most younger adults who experience an acute myocardial infarction (AMI) are sexually active before the AMI, but little is known about sexual activity or sexual function after the event. Objective: To describe patterns of sexual activity and function and identify indicators of the probability of loss of sexual activity in the year after AMI. Design, Setting, and Participants: Data from the prospective, multicenter, longitudinal Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study (conducted from August 21, 2008, to January 5, 2012) were assessed at baseline, 1 month, and 1 year. Participants were from US (n = 103) and Spanish (n = 24) hospitals and completed baseline and all follow-up interviews. Data analysis for the present study was conducted from October 15, 2014, to June 6, 2016. Characteristics associated with loss of sexual activity were assessed using multinomial logistic regression analyses. Main Outcomes and Measures: Loss of sexual activity after AMI. Results: Of the 2802 patients included in the analysis, 1889 were women (67.4%); median (25th-75th percentile) age was 49 (44-52) years (range, 18-55 years). At all time points, 637 (40.4%) of women and 437 (54.9%) of men were sexually active. Among people who were active at baseline, men were more likely than women to have resumed sexual activity by 1 month (448 [63.9%] vs 661 [54.5%]; P < .001) and by 1 year (662 [94.4%] vs 1107 [91.3%]; P = .01) after AMI. Among people who were sexually active before and after AMI, women were less likely than men to report no sexual function problems in the year after the event (466 [40.3%] vs 382 [54.8%]; P < .01). In addition, more women than men (211 [41.9%] vs 107 [30.5%]; P < .01) with no baseline sexual problems developed 1 or more incident problems in the year after the AMI. At 1 year, the most prevalent sexual problems were lack of interest (487 [39.6%]) and trouble lubricating (273 [22.3%]) among women and erectile difficulties (156 [21.7%]) and lack of interest (137 [18.8%]) among men. Those who had not communicated with a physician about sex in the first month after AMI were more likely to delay resuming sex (adjusted odds ratio [AOR], 1.51; 95% CI, 1.11-2.05; P = .008). Higher stress levels (AOR, 1.36; 95% CI, 1.01-1.83) and having diabetes (AOR, 1.90; 95% CI, 1.15-3.13) were significant indicators of the probability of loss of sexual activity in the year after the AMI. Conclusions and Relevance: Impaired sexual activity and incident sexual function problems were prevalent and more common among young women than men in the year after AMI. Attention to modifiable risk factors and physician counseling may improve outcomes.

Gender differences in pre-event health status of young patients with acute myocardial infarction: A VIRGO study analysis.

AIMS: We assessed gender differences in pre-event health status (symptoms, functioning, quality of life) in young patients with acute myocardial infarction and whether or not this association persists following sequential adjustment for important covariates. We also evaluated the interaction between gender and prior coronary artery disease, given that aggressive symptom control is a cornerstone of care in those with known coronary disease. METHODS AND RESULTS: A total of 3501 acute myocardial infarction patients (2349 women) aged 18-55 years were enrolled from 103 US/24 Spanish hospitals (2008-2012). Clinical/health status information was obtained by medical record abstraction and patient interviews. Pre-event health status was measured by generic (Short Form-12, EuroQoL) and disease-specific (Seattle Angina Questionnaire) measures. T-test/chi-square and multivariable linear/logistic regression analysis was utilized, sequentially adjusting for covariates. Women had more co-morbidities and significantly lower generic mean health scores than men (Short Form-12 physical health = 43 ± 12 vs. 46 ± 11 and mental health = 44 ± 13 vs. 48 ± 11); EuroQoL utility index = 0.7 ± 0.2 vs. 0.8 ± 0.2 and visual analog scale = 63 ± 22 vs. 67 ± 20, P < 0.0001 for all. Their disease-specific health status was also worse, with more angina (Seattle Angina Questionnaire angina frequency = 83 ± 22 vs. 87 ± 18), worse physical function (physical limitation = 78 ± 27 vs. 87 ± 21) and poorer quality of life (55 ± 25 vs. 60 ± 22, P<0.0001 for all). In multivariable analysis, the association between female gender and worse generic physical/mental health persisted, as well as worse disease-specific physical limitation and quality of life. The interaction between gender and prior coronary artery disease was not significant in any of the health status outcomes. CONCLUSION: Young women have worse pre-event health status as compared with men, regardless of their coronary artery disease history. While future studies of gender differences should adjust for baseline health status, an opportunity may exist to better address the pre-event health status of women at risk for acute myocardial infarction.

Frequency and Effects of Excess Dosing of Anticoagulants in Patients ≤55 Years With Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention (from the VIRGO Study).

Excess dosing of anticoagulant agents has been linked to increased risk of bleeding after percutaneous coronary intervention (PCI) for women compared with men, but these studies have largely included older patients. We sought to determine the prevalence and gender-based differences of excess dosing of anticoagulants including glycoprotein IIb/IIIa inhibitors, bivalirudin, and unfractionated heparin in young patients with acute myocardial infarction who underwent PCI and to examine its association with bleeding. Of 2,076 patients enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients study who underwent PCI, we abstracted doses of unfractionated heparin, bivalirudin, and glycoprotein IIb/IIIa inhibitors administered during PCI from the medical records. At least 47.2% received at least 1 excess dose of an anticoagulant, which did not differ by gender. We used logistic regression to determine the predictors of excess dosing and the association of excess dosing with bleeding. In multivariable analysis, only lower body weight and younger age were significant predictors of excess dosing. Bleeding was higher in young women who received excess dosing versus those who did not (9.3% vs 6.0%, p = 0.03) but was comparable among men (5.2% vs 5.9%, p = 0.69) in univariate analysis. In multivariable analysis, there was a trend to an association between excess dosing and bleeding (odds ratio 1.33, 95% confidence interval 0.92 to 1.91) although not statistically significant. In conclusion, approximately half of the patients received excess dosing of anticoagulant drugs during PCI, which did not vary based on gender. There was a trend toward an association between excess dosing and increased bleeding, although not statistically significant.

Insurance and Prehospital Delay in Patients ≤55 Years With Acute Myocardial Infarction.

This prospective study assessed whether gender differences in health insurance help explain gender differences in delay in seeking care for patients in the US, with acute myocardial infarction (AMI). We also assessed gender differences in such prehospital delay for AMI in Spain, a country with universal insurance. We used data from 2,951 US and 496 Spanish patients aged 18 to 55 years with AMI. US patients were grouped by insurance status: adequately insured, underinsured, or uninsured. For each country, we assessed the association between gender and prehospital delay (symptom onset to hospital arrival). For the US cohort, we modeled the relation between insurance groups and delay of >12 hours. US women were less likely than men to be uninsured but more likely to be underinsured, and a larger proportion of women than men experienced delays of >12 hours (38% vs 29%). We found no association between insurance status and delays of >12 hours in men or women. Only 17.3% of Spanish patients had delays of >12 hours, and there were no significant gender differences. In conclusion, women were more likely than men to delay, although it was not explained by differences in insurance status. The lack of gender differences in prehospital delays in Spain suggests that these differences may vary by health care system and culture.

Trends in acute myocardial infarction in young patients and differences by sex and race, 2001 to 2010.

BACKGROUND: Various national campaigns launched in recent years have focused on young women with acute myocardial infarctions (AMIs). Contemporary longitudinal data about sex differences in clinical characteristics, hospitalization rates, length of stay (LOS), and mortality have not been examined. OBJECTIVES: This study sought to determine sex differences in clinical characteristics, hospitalization rates, LOS, and in-hospital mortality by age group and race among young patients with AMIs using a large national dataset of U.S. hospital discharges. METHODS: Using the National Inpatient Sample, clinical characteristics, AMI hospitalization rates, LOS, and in-hospital mortality were compared for patients with AMI across ages 30 to 54 years, dividing them into 5-year subgroups from 2001 to 2010, using survey data analysis techniques. RESULTS: A total of 230,684 hospitalizations were identified with principal discharge diagnoses of AMI in 30- to 54-year-old patients from Nationwide Inpatient Sample data, representing an estimated 1,129,949 hospitalizations in the United States from 2001 to 2010. No statistically significant declines in AMI hospitalization rates were observed in the age groups <55 years or stratified by sex. Prevalence of comorbidities was higher in women and increased among both sexes through the study period. Women had longer LOS and higher in-hospital mortality than men across all age groups. However, observed in-hospital mortality declined significantly for women from 2001 to 2010 (from 3.3% to 2.3%, relative change 30.5%; p for trend < 0.0001) but not for men (from 2% to 1.8%, relative change 8.6%; p for trend = 0.60). CONCLUSIONS: AMI hospitalization rates for young people have not declined over the past decade. Young women with AMIs have more comorbidity, longer LOS, and higher in-hospital mortality than young men, although their mortality rates are decreasing.

Variation in recovery: Role of gender on outcomes of young AMI patients (VIRGO) study design.

BACKGROUND: Among individuals with ischemic heart disease, young women with an acute myocardial infarction (AMI) represent an extreme phenotype associated with an excess mortality risk. Although women younger than 55 years of age account for less than 5% of hospitalized AMI events, almost 16 000 deaths are reported annually in this group, making heart disease a leading killer of young women. Despite a higher risk of mortality compared with similarly aged men, young women have been the subject of few studies. METHODS AND RESULTS: Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) is a large, observational study of the presentation, treatment, and outcomes of young women and men with AMI. VIRGO will enroll 2000 women, 18 to 55 years of age, with AMI and a comparison cohort of 1000 men with AMI from more than 100 participating hospitals. The aims of the study are to determine sex differences in the distribution and prognostic importance of biological, demographic, clinical, and psychosocial risk factors; to determine whether there are sex differences in the quality of care received by young AMI patients; and to determine how these factors contribute to sex differences in outcomes (including mortality, hospitalization, and health status). Blood serum and DNA for consenting participants will be stored for future studies. CONCLUSIONS: VIRGO will seek to identify novel and prognostic factors that contribute to outcomes in this young AMI population. Results from the study will be used to develop clinically useful risk-stratification models for young AMI patients, explain sex differences in outcomes, and identify targets for intervention.