IM-JOVEN indicates Infarto de miocardio en la Mujer JOVEN.
aPatients were eligible and enrolled but did not complete baseline interviews.
bData on death are missing for 64 VIRGO participants (47 women; 17 men); data are complete for IM-JOVEN.
cAnalytic sample: VIRGO and IM-JOVEN participants with completed baseline, 1-month, and 1-year interviews.
Changes in categorical variables across the partnership (A), sexual activity (B), patient-physician communication about sex (C), and sexual problems (D) over time. The black dashed lines running across the bars allow the reader to follow the same group of individuals over time, for example, participants who were partnered (A) at baseline (blue) vs those who were not partnered at baseline (orange). The numbers below each bar graph provide the marginal distribution of a variable at each time point; this information can be inferred from the bar graph by summing the proportions indicated by each section of the bar of the same color. For example, most individuals who were unpartnered (A) at baseline were unpartnered over the course of the year following acute myocardial infarction. Most of those who were partnered at baseline stayed partnered across time, although there was more movement in this group.
eTable 1. Description and Timeline of Data Collection Domains and Measures
eTable 2. Demographic, Psychosocial, Health and Sexuality Characteristics of VIRGO Participants Who Were Sexually Active at Baseline, Stratified by Resumption Group
eTable 3. Additional Gender Combined Models of Loss of Sexual Activity After an AMI
eTable 4. Predicted Probability of Resumption Status Based on Various Scenarios
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Lindau ST, Abramsohn E, Bueno H, et al. Sexual Activity and Function in the Year After an Acute Myocardial Infarction Among Younger Women and Men in the United States and Spain. JAMA Cardiol. 2016;1(7):754–764. doi:10.1001/jamacardio.2016.2362
Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
For younger people who have an acute myocardial infarction (AMI), what factors determine resumption of sexual activity in the following year?
This longitudinal study of 2802 individuals in the United States and Spain found that patients who did not report a discussion with their physician about sex in the month after AMI were significantly more likely to delay resumption. Higher stress levels and diabetes were significant determinants of loss of sexual activity in the year after AMI.
Attention to modifiable risk factors and physician counseling may improve sexual outcomes after AMI.
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.
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.
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.
Nearly 20% of acute myocardial infarctions (AMIs) occur among people aged 18 to 55 years, one-third of whom are women.1 The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study, a multicenter, prospective, longitudinal study of US and Spanish patients in this age group, was designed to investigate differences between women and men in trajectories of functional recovery, including sexual activity and function, in the year after an AMI. In a 1-month outcome study from VIRGO2 and in another study including older AMI patients,3 most survivors were sexually active in the year before their event and many (40% of women, >55% of men) resumed sexual activity in the following year. We have also found that patients of all ages with AMI value their sexual function and want to know what level of function to expect during recovery from an AMI.2-4 Accordingly, US5,6 and European7 AMI guidelines recommend that physicians counsel patients about resuming sex after AMI. However, little is known about patterns of sexual recovery or sexual problems after AMI, particularly for younger patients.
To inform patient counseling and expectations about sexual recovery, we describe, for what we believe to be the first time, patterns of and gender differences in sexual activity and problems among younger patients in the year after an AMI. Prior studies2,3 showed that women were less likely than men to receive counseling about sex after an AMI, and demonstrated the importance of counseling for resumption of sexual activity. Extending these findings, we hypothesized that, in the year after AMI, (1) women would be more likely than men to resume sexual activity late or not at all and (2) women would be more likely than men to report sexual problems. We also examined predictors of loss of sexual activity in the year following AMI to determine potentially modifiable factors.
The VIRGO study has been previously described (clinicaltrials.gov Identifier: NCT00597922).8 Briefly, hospitalized patients aged 18 to 55 years with AMI were recruited between August 21, 2008, and January 5, 2012, to participate in VIRGO (named Infarto de miocardio en la Mujer JOVEN IM-JOVEN] in Spain to reflect separate public funding). The US study included 2985 participants (2009 women [67.3%]) enrolled at baseline at 103 sites; the Spain study included 516 participants (340 women [65.9%]) enrolled at baseline at 24 sites. Eligible patients had increased cardiac biomarkers (preferably troponin), with at least 1 biomarker above the 99th percentile of the upper reference limit within 24 hours of admission. Additional evidence of acute ischemia was required, including at least 1 of the following: ischemia symptoms, electrocardiogram changes indicative of new ischemia (new ST-segment or T-wave changes, new or presumably new left bundle branch block, or the development of pathologic Q waves). Patients must have presented directly to the enrolling site or been transferred within 24 hours of presentation to ensure that primary clinical decision making occurred at the enrolling site. Patients who were incarcerated, did not speak English or Spanish, were unable to provide informed consent or be contacted for follow-up, developed elevated cardiac markers because of elective coronary revascularization, or had an AMI resulting from physical trauma were excluded. The overall participation rate was 64.6% among 5422 individuals meeting the eligibility criteria (VIRGO, 2985 [61.7%]; and IM-JOVEN, 516 [88.2%]). The study sample was limited to 2802 VIRGO participants with data at baseline, 1 month, and 1 year (Figure 1). Institutional review board approval was obtained at each participating institution; patients provided written informed consent to participate and received financial compensation. The Yale Human Investigation Committee provided approval of the present study.
A detailed description of measures, including derived and calculated variables, is provided in eTable 1 in the Supplement. The Perceived Stress Scale (PSS) was evaluated at baseline and 1 year to assess stress; a higher score (range 0-34) indicates a greater likelihood that perceived stressors were beyond one’s coping mechanisms.9 The 9-item Patient Health Questionnaire (PHQ-9) was evaluated at baseline and 1 year to assess depressive symptoms; a score of 10 or higher indicates depressive symptoms.10 Elements of the Global Registry of Acute Coronary Events (GRACE) Risk Score (age, heart rate, systolic blood pressure, initial creatinine level, congestive heart failure, ST-segment deviation, previous AMI, percutaneous coronary intervention, and cardiac enzyme levels) were prospectively collected from the medical record at baseline and used to predict 6-month mortality in survivors of acute coronary syndrome; a higher GRACE risk score indicates increased risk.11 The 12-item Short-Form Health Survey Physical Composite Score (SF-12 PCS) was evaluated at baseline and 1 year to assess physical function during the 4 weeks before administration of the scale; a higher score indicates better function.12
Interviewers elicited demographic, psychosocial, and health characteristics at baseline, 1 month, and 1 year. Self-reported race information was obtained on enrollment, and race was analyzed as a potential indicator of sexual outcomes. Baseline interviews were conducted in person during the index hospitalization; follow-up interviews were conducted via telephone. Sexuality characteristics were measured using items adapted from prior large-scale, interviewer-administered studies of adult sexuality.2,3,13,14 As in those prior studies, sexual activity was defined as “any mutually voluntary activity with another person that involves sexual contact, whether or not intercourse or orgasm occurs.” Refusal/missing rates for sexual activity, importance, frequency, function, and communication items were 0.2% to 8.6%; refusal/missing rates for attitudinal items (fear, interest in emotional closeness, initiation of sex, and sexual satisfaction) were 0.7% to 12.0%.
This analysis used baseline, 1-month, and 1-year data; 2802 participants (80.0%) completed both 1-month and 1-year follow-up interviews (Figure 1). Descriptive, bivariate analyses were used to compare differences between women and men (the terms female and male are also used to indicate gender) in baseline and 1-year post-AMI demographic, psychosocial, and health characteristics; 1-year post-AMI sexual activity, sexual function, and importance; and communication with a physician about sex since the AMI. Country-level comparisons were also made. Categorical data are presented as frequencies and percentages. Differences between women and men as well as countries were compared using 2-sided χ2 or Fisher exact tests, as appropriate. Comparisons of physician recommendations about sex between 1 month and the interval between 1 month and 1 year were also made using the McNemar test to take into account the correlations between these 2 time points. Continuous variables are reported as mean (SD) or median, and 25th to 75th percentile differences were compared using unpaired t tests and Wilcoxon rank sum tests. Patterns of partnership, sexual activity, patient-physician communication about sexual activity, and sexual problems over time were summarized overall and separately by women vs men.
Among individuals who were sexually active before the AMI, loss of sexual activity was classified into 4 groups (eTable 2 in the Supplement). Group 1 (early resumers) included respondents who were sexually active in the 12 months before the AMI and at both 1 month and 1 year after the AMI. Group 2 (early resumers with later loss) were respondents who were sexually active in the 12 months before the AMI, had resumed sexual activity by 1 month after the AMI, but did not report sexual activity at 1 year after the AMI. Group 3 (late resumers) had been sexually active in the 12 months before the AMI and had not resumed sexual activity by 1 month after the AMI but reported sexual activity at 1 year. Group 4 (never resumers) consisted of respondents who were sexually active in the 12 months before the AMI but did not resume sexual activity at any time in the year following the AMI.
Bivariate analysis was first used to compare differences across these 4 groups. To further explore differences between women and men, multinomial logistic models were built and tested sequentially to assess how the effect of women vs men was attenuated and identify indicators of the probability of loss of sexual activity in the year after the AMI. Group 1 (early resumers) was the reference group; group 2 was excluded owing to the small sample size. The model covariates (eTable 1 in the Supplement) were selected based on clinical judgment and their association with the outcome in prior studies: gender (subjectively assessed, coded as female or male), age, country, partnership status, race, depression, stress, self-reported physical function, hypertension, diabetes, presence of at least 1 sexual problem, communication with a physician at 1 month after the AMI, and fearful of another AMI at 1 year after the AMI.
Initially, 8 models were tested using these covariates. Data from 5 models are presented in eTable 3 in the Supplement; 3 models are presented here: (1) model 1 included gender only; (2) model 2 included gender and country plus baseline demographic, psychosocial, and health characteristics; communication with a physician about sexual activity at 1 month; presence of at least 1 sexual problem at baseline; and fearful of another AMI at 1 year; and (3) model 3 included all of the covariates included in model 2 as well as 2 interactions: gender (female or male) by partnership status and age by country. All interactions with gender and interactions between country and age, partnership status, and communication with physician at 1 month after the AMI, between communication with physician at 1 month after the AMI and fearful of another AMI at 1 year after the AMI were tested, and nonsignificant interactions were removed from the final model (model 3). To aid in interpretation of the model results, adjusted predicted probabilities of early resumers, late resumers, and never resumers were generated from model 3 for partnered/unpartnered women and partnered/unpartnered men with other continuous covariates set to their mean and categorical variables set to their reference except for race, which was held constant at white race (eTable 4 in the Supplement). A generalized Hosmer-Lemeshow goodness-of-fit test for multinomial logistic regression models was conducted.15
Comparing participants in the VIRGO study with nonparticipants (those who completed screening but declined further participation), participants were more likely to be younger (median [25th-75th percentile] age, 48 [44-52] vs 49 [44-52] years), female (2397 [67.1%] vs 1156 [57.4%]), and white (2852 [79.8%] vs 1493 [74.2%]). The age range in the patients included in the analysis was 18 to 55 years. Comparing persons in the analytic sample for this study (limited to people who had baseline, 1-month, and 1-year data) with those who were excluded from the analytic sample owing to insufficient data, those in the analytic sample were more likely to be older (median age, 48 [44-52] vs 47 [42-51] years), white (2231 [79.6%] vs 511 [73.1%]), and partnered (1691 [60.6%] vs 338 [48.4%]). The gender distribution was similar between the analytic sample (female, 1889 [67.4%]; male, 913 [32.6%]) and the excluded population (female, 460 [65.8%]; male, 329 [34.2%]).
P values were 2-sided and not adjusted for multiple testing. All analyses were conducted using SAS, version 9.3 (SAS Institute Inc) or Stata, release 13 (StataCorp) and VIRGO data version 1.0. Data analysis was performed from October 15, 2014, to June 6, 2016.
Table 1 summarizes participants’ baseline and, where appropriate, 1-year demographic, psychosocial, and health characteristics by gender and country. Almost half of the women (892 [49.5%]) and 526 [60.3%] of the men were partnered at all 3 time points (Figure 2A). Although the age distribution was similar across gender and country groups, significantly fewer women (1083 [57.5%] vs 608 men [67.0%] at baseline; 970 [53.3%] vs 569 men [64.4%] at 1 year) and US patients (1392 [58.5%] vs 299 Spanish patients [73.3%] at baseline; 1221 [53.4%] vs 318 Spanish patients [76.6%] at 1 year) were married or cohabiting (P < .001 for all comparisons) both at baseline and 1 year. Similar to baseline, both in the United States and Spain, women had higher rates of stress and depression at 1 year and lower levels of physical functioning compared with men.
Overall, most women and men (1255 [72.6%] vs 731 [85.2%]; P < .001) were sexually active 1 year after AMI (Table 2); 637 women (40.4%) and 437 men (54.9%) were sexually active at all 3 time points (Figure 2B). Among the subgroup of those who were sexually 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. However, patients in the United States were less likely to be sexually active at 1 year than were those in Spain (1630 [75.0%] vs 356 [86.0%]; P < .001). At 1 year, women were more likely to rate sex as “not at all important” (472 [27.3%] vs 64 [7.5%] men; P < .001).
In both countries, women were less likely to receive counseling about resuming sex at any time in the year after AMI (425 [26.7%] vs 341 men [41.2%]; P < .001) (Figure 2C). Compared with patients in the United States, Spanish patients were more likely to report having these discussions with a physician (123 [29.9%] vs 474 [22.1%]; P < .001) and that a physician initiated these discussions (49 [41.2%] vs 100 [20.1%]; P < .001). The recommendation to limit sex (34 [20.7%] vs 18 [11.0%]; P = .01), keep heart rate down (27 [16.5%] vs 16 [9.8%]; P = .04), and take a more passive role (39 [23.9%] vs 18 [11.0%]; P = .002) were more commonly reported at 1 month than for the interval between 1 month and 1 year; the recommendation to resume sex without limitations was less frequent at 1 month than for the interval between 1 month and 1 year (71 [43.3%] vs 93 [56.7%]; P = .02).
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). Among participants who were sexually active in the 11 months following their 1-month interview, most women (727 [59.4%]) and approximately half of the men (327 [45.7%]) reported at least 1 sexual problem. Of sexually active patients with no sexual problems at baseline, 318 (37.0%) developed 1 or more incident sexual problems in the year after the AMI (Figure 2D). The most prevalent sexual problems among women at 1 year were lack of interest (487 [39.5%]), trouble lubricating (273 [22.3%]), and difficulty breathing during intercourse (239 [19.5%]); the most prevalent problems among men were erectile difficulties (156 [21.7%]), lack of interest (137 [18.8%]), and feelings of anxiety about their sexual performance (113 [15.7%]). Few men (19 [2.9%] in the United States and 2 [1.4%] in Spain) reported use of medications to treat erectile dysfunction at baseline, 1 month, or 1 year after AMI.
Comparisons of the characteristics of the 4 resumption groups are provided in eTable 2 in the Supplement. In unadjusted, multinomial, logistic regression analyses of loss of sexual activity in the year following an AMI, women were more likely to delay resuming sex (by 1 year rather than by 1 month or to be a late resumer) compared with men (odds ratio [OR], 1.45; 95% CI, 1.15-1.81; P = .001); this finding persisted even after controlling for other demographic, psychosocial, health, and sexual characteristics (Table 3 and additional models in eTable 3 in the Supplement). However, a significant gender by partnership status interaction was found (P = .003): partnered women were more likely than partnered men to resume sex later (adjusted OR [AOR], 1.71; 95% CI, 1.29-2.25; P < .001), but there was not a significant gender difference for unpartnered individuals. Older age among this younger cohort was also significantly associated with greater odds of being a late resumer in the United States (AOR, 1.35; 95% CI, 1.10-1.67; P = .005) but not in Spain (AOR, 0.75; 95% CI, 0.50-1.12; P = .16; age by country interaction, P = .01). Overall, participants who had not communicated with a physician in the first month after their AMI were also more likely to be late resumers (AOR, 1.51; 95% CI, 1.11-2.05; P = .008).
Among people who were sexually active in the year before their AMI, women had higher odds of never resuming sexual activity in the year following the AMI than men (OR, 1.62; 95% CI, 0.98-2.69), but this finding was not significant after controlling for other demographic, psychosocial, health, and sexual characteristics (AOR, 1.29; 95% CI, 0.76-2.21) (Table 3). Older age, unpartnered status, higher stress levels, and diabetes were all significant indicators of the probability of never resuming sexual activity in the year following an AMI.
Our findings, based on 2-country data from VIRGO, indicate that most young women and men were partnered and sexually active in the year before and the year after an AMI. More than half of women (727 [59.4%]) and just under half of men (327 [45.7%]) had sexual function problems in the year after AMI; women were more likely than men to develop incident sexual function problems. Despite a high prevalence of sexual function problems, particularly among women, few participants reported having any conversation with a physician about resuming sex after an AMI.
The proportions of patients who were partnered and sexually active at baseline were similar to those reported in population-based studies of similarly aged people in the United States16 and a slightly older population in Spain.17 In the first month following AMI, 99 women (9.5%) and 37 men (6.3%) became unpartnered and a slightly lower proportion remained unpartnered at 1 year (75 women [7.2%]; 23 men [3.9%]). Prior studies18,19 have shown that a person’s spouse or intimate partner is an important social relationship for recovery or protection from illness and that lower levels of social support are associated with poorer AMI outcomes.20 Cardiac care providers should be aware that loss of a partner after AMI may impair the patient’s overall recovery and may require additional psychosocial support.
There was a significant decrease in sexual activity at 1 month after AMI compared with baseline, followed by a significant increase between 1 month and 1 year for both women and men. Although most people with AMI were sexually active by 1 year following the event, approximately 1 in 15 women (110 [6.7%]) and 1 in 20 men (39 [4.9%]) never resumed sexual activity during that time. In an earlier study3 by our group of an older US cohort of 1879 patients with AMI (mean [SD] age, 59.4 [11.7] years), 11% of women and 13% of men had not resumed sexual activity by 1 year. Combining these findings with those of the present study, women with AMI and men with AMI older than 60 years can be informed that approximately 90% of patients resume sexual activity by 1 year after an AMI. Men younger than 60 years can expect a 95% resumption rate by 1 year after an AMI. Among partnered people, women resumed sexual activity later than men. Unpartnered people resumed sexual activity later than did those with a partner. Overall, most patients had resumed sexual activity by 1 month. Patterns were similar in the United States and Spain.
Sexual function problems were prevalent before and after AMI in this cohort and generally higher than rates reported for the same age general population in the United States13 (we did not find comparable population-based data from Spain). A large proportion of women (211 [41.9%]) and men (107 [30.5%]) with no baseline sexual problems developed 1 or more incident sexual problems in the year after their AMI (P < .01). The rate of loss of sexual function after AMI was on a par with the loss of general physical function in this cohort (459 [46.1%] of people with the recommended level of physical activity at baseline had insufficient activity or inactivity at 1 year) and was several-fold higher than the incidence of depression after AMI (171 [9.8%]). Although it is important to advise patients that sexual problems may arise after AMI (most commonly lack of interest for women and erectile difficulties for men), cardiac care clinicians can give hope by communicating that 40% of women and 55% of men have no sexual function problems in the year after AMI and that nearly one-third of patients with problems in the year before AMI reported none in the year after.
Our group’s prior studies2,3 in the United States and Spain have shown that communication with a physician is a significant indicator of the probability of sexual activity after an AMI. As expected, communication rates at 1 year were higher for both women and men than those reported at 1 month but were still low. Spanish patients were more likely to report having these discussions and that a physician initiated the discussions. The nature of physician counseling changed over time; physicians in both countries were more cautious in their counseling in the 1 month following AMI compared with counseling in the interim between the participants' 1-month interview and their 12-month interview.
The present study shows that counseling was a significant indicator of time to resumption (early vs late), but stress and diabetes more strongly indicated the probability of never resuming sexual activity. These health conditions are known to have deleterious effects on overall outcomes after AMI21 as well as on female and male sexual function.13,21 Counseling patients that these conditions are associated with poorer sexual function outcomes might help to motivate adherence to cardiac rehabilitation, lifestyle changes, and other secondary prevention activities.
The findings should be interpreted in the context of several potential limitations. This study relied on patient self-report, which may have introduced recall bias. In our prior study,3 recall of discharge instructions about resuming sexual activity, compared with documentation in the medical records, did not differ by gender or sexual activity in the year following the AMI. Statistically significant differences in demographic characteristics were found between VIRGO participants and nonparticipants and between those in our analytic sample and those excluded from the sample, but the differences were small. Given the importance of gender in our analyses, it is reassuring that the distribution of gender was similar between the analytic sample and those who were excluded because of insufficient data. Nevertheless, a higher proportion of partnered people in the analytic sample could produce upward bias on the sexual activity and sexual problem estimates. Although partner factors can affect resumption of sexual activity after AMI,4 partner data were not collected. This study did not collect qualitative data. However, prior qualitative research4 corroborates that sexual problems after AMI are prevalent, fear could inhibit resumption, and patients want to be counseled about sex after AMI by their physician. Finally, a larger sample size and additional data would be needed to stratify by sexual orientation or identity as well as the partner’s gender and to model the effects on sexual outcomes of specific comorbidities, medications, procedures, tests, and effects of rehabilitation, prolonged or rehospitalization, or a subsequent AMI or other health event. Understanding the effect of these factors on sexual outcomes could allow for more-tailored counseling according to individual risk for loss of sexual activity or function after AMI.
Patients want to know what level of sexual function to expect during recovery from AMI. Our findings can be used to expand counseling and care guidelines5-7 to include recommendations for advising patients on what to expect in terms of post-AMI sexual activity and function. Attention to modifiable risk factors and improved physician counseling may be important levers for improving sexual function outcomes for young women and men after AMI.
Corresponding Author: Stacy Tessler Lindau, MD, MAPP, University of Chicago, 5841 S Maryland Ave, MC 2050, Chicago, IL 60637 (firstname.lastname@example.org).
Accepted for Publication: June 7, 2016.
Published Online: August 31, 2016. doi:10.1001/jamacardio.2016.2362
Author Contributions: Mss Strait and Zhou had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Acquisition, analysis, or interpretation of data: Lindau, Abramsohn, Bueno, D’Onofrio, Lichtman, Lorenze, Sanghani, Spatz, Strait, Wroblewski, Zhou, Krumholz.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Lindau, Strait, Wroblewski, Zhou.
Obtaining funding: Lindau, Bueno, D’Onofrio, Lichtman, Spertus, Krumholz.
Administrative, technical, or material support: Lindau, Abramsohn, Lorenze.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Krumholz is a recipient of research agreements from Medtronic and from Johnson & Johnson (Janssen) through Yale University to develop methods of clinical trial data sharing and is chair of a cardiac scientific advisory board for UnitedHealth and receives financial compensation for that position. Dr Bueno has received advisory/consulting fees from AstraZeneca, Bayer, BMS-Pfizer, Daichii-Sankyo, Eli-Lilly, Ferrer, Menarini, Novartis, and Servier. Dr Mehta Sanghani is on the advisory board and speaker’s bureau for Astellas Pharma, Inc and receives financial compensation for these positions. Dr Spertus is a member of the cardiac scientific advisory board for United Healthcare and has received financial compensation for that position; has received research grants from National Institutes of Health, Genentech, Gilead, ACCF, and Lilly; has provided consulting services for Novartis, Amgen, Gilead, and Janssen; and owns the copyright to the Seattle Angina Questionnaire. No other disclosures were reported.
Funding/Support: Support was provided by grant 1K23AG032870-01A1K23 from the National Institutes of Health/National Institute on Aging and private individual philanthropic funds to the Lindau Laboratory at the University of Chicago (Dr Lindau, Ms Abramsohn, and Ms Wroblewski), grant U01 HL105270-05 from the National Heart, Lung, and Blood Institute to the Center for Cardiovascular Outcomes Research at Yale University (Dr Krumholz), the Agency for Healthcare Research and Quality Patient Centered Outcomes Research Institutional Mentored Career Development Program grant K12HS023000 (Dr Spatz), and in part by grant BA08/90010 from the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III, Spain (Dr Bueno). VIRGO was supported by grant R01 HL081153 from the National Heart, Lung, and Blood Institute, Department of Health and Human Services; IM-JOVEN was supported in Spain by PI 081614 from the Fondo de Investigaciones Sanitarias del Instituto Carlos III, Ministry of Science and Technology, and by additional funds from the Centro Nacional de Investigaciones Cardiovasculares.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or the National Institute on Aging.
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