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.

The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) Classification System: A Taxonomy for Young Women With Acute Myocardial Infarction.

BACKGROUND: Current classification schemes for acute myocardial infarction (AMI) may not accommodate the breadth of clinical phenotypes in young women. METHODS AND RESULTS: We developed a novel taxonomy among young adults (≤55 years) with AMI enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study. We first classified a subset of patients (n=600) according to the Third Universal Definition of MI using a structured abstraction tool. There was heterogeneity within type 2 AMI, and 54 patients (9%; including 51 of 412 women) were unclassified. Using an inductive approach, we iteratively grouped patients with shared clinical characteristics, with the aims of developing a more inclusive taxonomy that could distinguish unique clinical phenotypes. The final VIRGO taxonomy classified 2802 study participants as follows: class 1, plaque-mediated culprit lesion (82.5% of women; 94.9% of men); class 2, obstructive coronary artery disease with supply-demand mismatch (2a: 1.4% women; 0.9% men) and without supply-demand mismatch (2b: 2.4% women; 1.1% men); class 3, nonobstructive coronary artery disease with supply-demand mismatch (3a: 4.3% women; 0.8% men) and without supply-demand mismatch (3b: 7.0% women; 1.9% men); class 4, other identifiable mechanism (spontaneous dissection, vasospasm, embolism; 1.5% women, 0.2% men); and class 5, undetermined classification (0.8% women, 0.2% men). CONCLUSIONS: Approximately 1 in 8 young women with AMI is unclassified by the Universal Definition of MI. We propose a more inclusive taxonomy that could serve as a framework for understanding biological disease mechanisms, therapeutic efficacy, and prognosis in this population.

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.

Disease and economic burden of surgery in desmoid tumors: a review.

INTRODUCTION: Desmoid tumors (DT) are soft-tissue tumors that infiltrate into surrounding structures with ill-defined margins. Although surgery is a potential treatment option, complete excision with negative margins is not often possible, the postsurgery recurrence rate is high, and surgery can result in disfigurement and/or loss of function. AREAS COVERED: We conducted a literature review to assess the burden of surgery in patients with DT, focusing on recurrence rates and functional deficits resulting from surgeries. Since economic data related to DT surgery is lacking, reviews of surgery costs in soft-tissue sarcomas and of general costs of amputations were conducted. Risk factors for DT recurrence after surgery are young age (<30 years), tumor location (extremities), tumor size (>5 cm in greatest diameter), positive resection margins, and history of trauma in the area of the primary tumor. Tumors in the extremities have the highest risk of recurrence (30%-90%). Lower rates of recurrences have been reported when radiotherapy was used after surgery (14%-38%). EXPERT OPINION: Although effective in specific cases, surgery may be associated with poor long-term functional outcomes and higher economic costs. Therefore, it is imperative to find alternative treatments with acceptable efficacy and safety profiles that do not adversely affect functional aspects in patients.

Trends in 30-Day Readmission Rates for Medicare and Non-Medicare Patients in the Era of the Affordable Care Act.

BACKGROUND: Temporal changes in the readmission rates for patient groups and conditions that were not directly under the purview of the Hospital Readmissions Reduction Program (HRRP) can help assess whether efforts to lower readmissions extended beyond targeted patients and conditions. METHODS: Using the Nationwide Readmissions Database (2010-2015), we assessed trends in all-cause readmission rates for 1 of the 3 HRRP conditions (acute myocardial infarction, heart failure, pneumonia) or conditions not targeted by the HRRP in age-insurance groups defined by age group (≥65 years or <65 years) and payer (Medicare, Medicaid, or private insurance). RESULTS: In the group aged ≥65 years, readmission rates for those covered by Medicare, Medicaid, and private insurance decreased annually for acute myocardial infarction (risk-adjusted odds ratio [OR; 95% confidence interval] among Medicare patients, 0.94 [0.94-0.95], among Medicaid patients, 0.93 [0.90-0.97], and among patients with private-insurance, 0.95 [0.93-0.97]); heart failure (ORs, 0.96 [0.96-0.97], 0.96 [0.94-0.98], and 0.97 [0.96-0.99], for the 3 payers, respectively), and pneumonia (ORs, 0.96 [0.96-0.97), 0.94 [0.92-0.96], and 0.96 [0.95-0.97], respectively). Readmission rates also decreased in the group aged <65 years for acute myocardial infarction (ORs: Medicare 0.97 [0.96-0.98], Medicaid 0.94 [0.92-0.95], and private insurance 0.93 [0.92-0.94]), heart failure (ORs, 0.98 [0.97-0.98]: 0.96 [0.96-0.97], and 0.97 [0.95-0.98], for the 3 payers, respectively), and pneumonia (ORs, 0.98 [0.97-0.99], 0.98 [0.97-0.99], and 0.98 [0.97-1.00], respectively). Further, readmission rates decreased significantly for non-target conditions. CONCLUSIONS: There appears to be a systematic improvement in readmission rates for patient groups beyond the population of fee-for-service, older, Medicare beneficiaries included in the HRRP.

Variation in and Hospital Characteristics Associated With the Value of Care for Medicare Beneficiaries With Acute Myocardial Infarction, Heart Failure, and Pneumonia.

Importance: Payers and policy makers have advocated for transitioning toward value-based payment models. However, little is known about what is the extent of hospital variation in the value of care and whether there are any hospital characteristics associated with high-value care. Objectives: To investigate the association between hospital-level 30-day risk-standardized mortality rates (RSMRs) and 30-day risk-standardized payments (RSPs) for acute myocardial infarction (AMI), heart failure (HF), and pneumonia (PNA); to characterize patterns of value in care; and to identify hospital characteristics associated with high-value care (defined by having lower than median RSMRs and RSPs). Design, Setting, and Participants: This national cross-sectional study applied weighted linear correlation to investigate the association between hospital RSMRs and RSPs for AMI, HF, and PNA between July 1, 2011, and June 30, 2014, among all hospitals; examined correlations in subgroups of hospitals based on key characteristics; and assessed the proportion and characteristics of hospitals delivering high-value care. The data analysis was completed in October 2017. The setting was acute care hospitals. Participants were Medicare fee-for-service beneficiaries discharged with AMI, HF, or PNA. Main Outcomes and Measures: Hospital-level 30-day RSMRs and RSPs for AMI, HF, and PNA. Results: The AMI sample consisted of 4339 hospitals with 487 141 hospitalizations for mortality and 462 905 hospitalizations for payment. The HF sample included 4641 hospitals with 960 960 hospitalizations for mortality and 903 721 hospitalizations for payment. The PNA sample contained 4685 hospitals with 952 022 hospitalizations for mortality and 901 764 hospitalizations for payment. The median (interquartile range [IQR]) RSMRs and RSPs, respectively, was 14.3% (IQR, 13.8%-14.8%) and $21 620 (IQR, $20 966-$22 567) for AMI, 11.7% (IQR, 11.0%-12.5%) and $15 139 (IQR, $14 310-$16 118) for HF, and 11.5% (IQR, 10.6%-12.6%) and $14 220 (IQR, $13 342-$15 097) for PNA. There were statistically significant but weak inverse correlations between the RSMRs and RSPs of -0.08 (95% CI, -0.11 to -0.05) for AMI, -0.21 (95% CI, -0.24 to -0.18) for HF, and -0.07 (95% CI, -0.09 to -0.04) for PNA. The largest shared variance between the RSMRs and RSPs was only 4.4% (for HF). The correlations between the RSMRs and RSPs did not differ significantly across teaching status, safety-net status, urban/rural status, or the proportion of patients with low socioeconomic status. Approximately 1 in 4 hospitals (20.9% for AMI, 23.0% for HF, and 23.9% for PNA) had both lower than median RSMRs and RSPs. Conclusions and Relevance: These findings suggest that there is significant potential for improvement in the value of AMI, HF, and PNA care and also suggest that high-value care for these conditions is attainable across most hospital types.

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.

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.

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.

Depressive symptoms in younger women and men with acute myocardial infarction: insights from the VIRGO study.

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.