Nancy P. Lorenze

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.

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.

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 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.

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.

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.

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.

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.

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.