CCDG CVD: VIRGO - Variation in Recover-Role of Gender on Outcomes of Young Acute Myocardial Infarction (AMI) Patients

The VIRGO study is a four year research project funded by the NHLBI to study young women and men with heart attacks. A total of 2,000 women who are 18 - 55 years of age and a smaller comparison group of 1,000 similarly aged men will be enrolled in this multi-site observational study from approximately 120 different hospitals across the country. Young women have a much greater risk of dying after an acute myocardial infarction (AMI) than similarly aged men. Their mortality risk is markedly higher than that of young men, and limited data on young minority women suggest that they may have the highest risk of any young subgroup. Findings from the small number of published studies of young women with ischemic heart disease suggest that the biology, epidemiology, care, and outcomes of this group are distinct from those of men. To date, there have been no large studies of this population, even as the death toll is comparable to that from breast cancer in this country. This study will help researchers identify key factors that influence recovery from a heart attack and potentially improve the care and outcomes of young women and men with AMI. Specific Aims: To investigate the excess risk in young women with AMI and to identify key demographic, clinical, metabolic, psychosocial, health care delivery, and biological determinants of prognosis, we propose a national, prospective, observational study of 2,000 women who are 55 years or younger with AMI and a smaller comparison group of 1,000 men. Our prior work and preliminary studies indicate that the sex differences are most prominent in this age group and suggest that by 1 year after discharge, there are substantial sex differences in outcomes. We will also develop risk stratification tools that will help clinicians to identify young women with the highest and lowest risk. Specific Aim 1: Determine sex differences in outcomes following AMI. Specific Aim 2: Determine sex differences in the prevalence and prognostic importance of demographic, clinical, and psychosocial risk factors. Specific Aim 3:Determine sex differences in quality of care. Specific Aim 4: Determine sex differences in the prevalence and prognostic importance of selected biochemical biomarkers following AMI. These samples have been whole genome sequenced as part of the NHGRI's Center for Common Disease Genetics at the Broad Institute.]]>
INCLUSION CRITERIA ------------------------------------------------------------------------------------------------------------ Age 18-55 AMI Criteria: Must meet both of the following criteria (2.1 AND 2.2) 2.1 Need at least one of the following elevated markers of myocardial necrosis: Troponin I or T level greater than the 99th percentile of the upper reference limit (URL) CK level > twice the upper reference limit (URL) with CK-MB activity level > 10% total CK value on the same draw or CK-MB mass greater than the 99th percentile of URL Do NOT include the following: Post-PCI cardiac markers with no pre-existing ACS in the past 24h Post-CABG cardiac markers with no pre-existing AMI 2.2 Supporting evidence of myocardial ischemia with at least one of the following: Symptoms of ischemia ECG changes indicative of new ischemia (New ST-T changes; New or presumably new left bundle branch block (LBBB); Development of pathological Q waves) Other evidence of pathological necrosis (imaging, pathology) Presentation: Must meet one of the following two criteria: Patient presented initially at this facility Patient was transferred here from another facility with 24h of original presentation EXCLUSION CRITERIA ------------------------------------------------------------------------------------------------------------ Patients are excluded if any of the following criterion was met: Patient previously enrolled in VIRGO Non-English/non-Spanish speaking Inability to provide informed consent Inability to contact for follow-up (e.g. no access to phone, not planning on living in the country for next year) Acute MI due to chest trauma Currently a prisoner Other reason ]]>
Almost 16,000 U.S. women aged 55 years or younger die prematurely each year from coronary heart disease (CHD), ranking it among the leading causes of death in this group. CHD affects a small overall percentage of young women with potentially unknown biological and environmental factors that may influence its presentation and course. The risk of death after acute myocardial infarction (AMI) in women compared with men varies with age, but only among the younger age groups. During hospitalization, women aged 55 years and younger are about twice as likely to die as men of similar age. Among those who survive, their subsequent mortality risk is about 50% higher than men. In our preliminary studies, minority women aged 55 years and younger have an even higher risk of adverse outcomes than non-minority women. Our group has documented the age - sex interaction in 3 key retrospective studies. In our initial study of 1,025 patients with AMI admitted to 15 Connecticut hospitals, younger women had a higher risk of in-hospital death than men of similar age, whereas the risk was lower among older women than among older men. Data from 384,878 patients in the National Registry of Myocardial Infarction (NRMI) suggests further evidence for a strong age - sex interaction, with the risk of in-hospital mortality in the youngest women (age <50 years) about twice that of similarly aged men. Sex differences in medical history, clinical severity of the infarction, and early management accounted for only about one-third of this difference. To evaluate whether these differences persist among hospital survivors of an AMI, we also studied 6,826 patients in the Worcester Heart Attack Study. Women aged 50 or younger had a nearly 50% greater risk of death within 2 years after discharge than men did; women aged 60 years or older, however, did not have this excess risk compared with men. Despite reporting sex differences in mortality among younger patients, these retrospective studies have important limitations such as a lack of information about a broad range of variables that might explain the sex differences, including the prevalence and severity of a comprehensive list of CHD risk factors, clinical characteristics, quality of medical care, demographic and psychosocial factors, as well as interventions (including medications for secondary prevention) after hospital discharge. We were therefore unable to assess the role of biological and environmental factors (including health status, symptom burden and social roles) in contributing to the higher risk of post-AMI adverse outcomes in young women than in young men. This gap in knowledge is particularly important because patients are concerned about both quality of life as with quantity and because many therapies, including revascularization, are used primarily to improve health status. Data on minority women, though thoroughly lacking, suggest that they bear an even greater burden of heart disease than white women. The CDC reports that young black women are more highly represented among those with AMI, in addition the impact of heart disease is substantial, with heart-disease mortality from 1991 through 1995 of 553 per 100,000 for black women and 401 per 100,000 for all women. The Heart and Estrogen/progestin Replacement Study (HERS), a randomized trial of hormone replacement therapy in postmenopausal women, found that the risk for cardiovascular death or AMI during 4 years of follow-up was twice as high among black women as among white women (HR, 2.05; 95% CI, 1.52 to 2.77). The role of demographic, clinical, and psychosocial factors on the excess risk in young women, particularly minority women, except for age has been understudied. In particular, socioeconomic status and work/home roles including providing care to their children and elderly parents could play an important prognostic role in young women. In addition, low educational attainment, double work loads of employment and family are more powerful risk factors for post-AMI adverse outcomes in older women compared with older men. The little information we have derives from older populations and does suggest that certain clinical risk factors (smoking, diabetes, glucose intolerance, elevated cholesterol, and LV hypertrophy) are more prevalent and associated with greater mortality risk in women with CHD than in men with CHD. In fact, several studies have shown that the relative risk of CHD in diabetic women varies from 3-7 as compared with 2-3 in diabetic men, especially important for minority women in which the prevalence of type II diabetes is 2-4 times that of white women. Clinical presentation by sex may be different, though no study has focused on younger women. As Canto and colleagues have shown, in a study of all ages, that women are also less likely than men to present with chest pain and more likely to have other symptoms such as nausea and vomiting during an AMI, thus less likely to be referred by lay consultants for medical care. These differences may be the cause of longer time to diagnosis and delays (or omissions) in the administration of life-saving therapies such as aspirin, beta-blockers, fibrinolytic therapy, and revascularization. Despite the lack of studies comparing sex-risk factor interactions, psychosocial factors such as character traits (e.g. optimism), feelings of control, and social and emotional support may play an important role in the outcomes of women after AMI. Depression and lack of social support have been shown to be important risk factors for post-AMI adverse outcomes in older women than in older men. Sex differences in access to care and quality of care in this patient population are relatively unstudied. Obstacles to high-quality care for women may relate to personal preferences or beliefs, baseline comorbidity, differences in the perception and reporting of their symptoms, lack of coordination with diverse caregivers (e.g., internists, cardiologists, and gynecologists), and poor advice from lay consultants. Although we know little about these issues in young women with AMI, studies have shown that women with chest pain may be less likely to be referred by lay consultants for medical care and some procedures are performed less often for women with AMI compared with men, but whether gender is independently associated with referral for an indicated procedure is controversial Biological factors related to ischemic heart disease vary by sex. Studies suggest that the biology of young women with heart disease may be different from men and older patients. Young women with sudden cardiac death are more likely to have coronary plaque erosion; plaque rupture, on the other hand, is more common in men and in older women. Marenberg and colleagues have shown in a Yale study of 21,004 Swedish twins that heredity is a powerful predictor of CHD death in both sexes but the risk for CHD death is significantly higher in women. Limited progress has been made in the elucidation of specific genes involved in sex-specific risk of AMI, however all of the genetic variants share direct or indirect prothrombotic effects, potentiated by smoking, suggesting that thrombosis risk may be central to the pathogenesis of AMI in women. Confirmation of the prognostic value of these genetic markets in large samples is needed before declaring these genes to be significant risk factors. Creating a DNA bank will be valuable resource for future studies investigating specific genes involved in sex-specific risk of AMI. The importance of various inflammatory biomarkers, lipid and metabolic measures, and the role of sex hormones in explaining the excess risk have not been examined in any large study of young women. The Women's Ischemia Syndrome Evaluation (WISE), a study of premenopausal women undergoing coronary angiography for evaluation for suspected ischemia, reported that hypoestrogenemia of hypothalamic origin is associated with Coronary Artery Disease (CAD) in this group, a finding which supports the concept that female protection is lost when ovarian function is disrupted. In premenopausal women, it has been proposed that they may be at greater risk of MI during the menstrual or follicular phase of their ovarian cycle during which their estradiol blood -levels are the lowest. While far from definitive, several studies have found an association of low 17β-estradiol levels and increased risk of acute coronary event. When women of the Determinants of Myocardial Infarction Onset Study (ONSET Study) were followed, they found a relative risk of 3.3 for having an acute MI during the early follicular phase of menses.]]>