Heart Disease In Women Research Articles

Risk of heart disease following treatment for breast cancer - results from a population-based cohort study.

There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, and ischemic heart disease in women diagnosed with breast cancer. A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model. Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy. Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices. This work was supported by the Swedish Research Council (grant no: 2018-02547); Swedish Cancer Society (grant no: CAN-19-0266); and FORTE (grant no: 2016-00081).

The life course perspective of gestational diabetes: An opportunity for the prevention of diabetes and heart disease in women.

SummaryGestational diabetes mellitus (GDM), which has traditionally been defined as glucose intolerance of varying severity with first onset in pregnancy, is rising in prevalence with maternal hyperglycemia currently affecting one in every six pregnancies worldwide. Although often perceived as a medical complication of pregnancy, GDM is actually a chronic cardiometabolic disorder that identifies women who have an elevated lifetime risk of ultimately developing type 2 diabetes and cardiovascular disease. In identifying high-risk women early in the natural history of these conditions, the diagnosis of GDM raises the tantalizing possibility of early intervention and risk modification. However, before such promise can be realized in practice, a series of clinical challenges/obstacles (reviewed herein) must be overcome. Ultimately, the coupling of this life course perspective of GDM with concerted efforts to overcome these challenges may enable fulfilment of this unique opportunity for the primary prevention of diabetes and heart disease in women.

Menstrual cycle regularity as a predictor for heart disease and diabetes: Findings from a large population-based longitudinal cohort study.

Menstrual cycle regularity underpins the diagnosis of polycystic ovary syndrome (PCOS), which is linked to adverse cardio-metabolic profile. However, links between menstrual disorders and metabolic conditions are often under-appreciated and not considered when assessing cardio-metabolic risk in women. We aimed to assess the risk of diabetes and heart disease in women with irregular menstrual cycles and those whose cycles were regular. This was a community based longitudinal cohort study. We utilized the 1946 to 1951 birth cohort database (N = 13,714) of the Australian Longitudinal Study on Women's Health (ALSWH) over a 20-year follow-up period. Data were analysed using Cox regression models. Women with irregular menstrual cycles had 20% higher risk of developing heart disease [adjusted hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01-1.43) compared with those with regular menstrual cycles. We also observed 17% higher risk of diabetes (HR: 1.17, 95% CI: 1.00-1.38) in women who had irregular menstrual cycles than in women who had regular menstrual cycles. The diabetes risk was 30% higher (HR: 1.30, 95% CI: 1.09-1.55) if women had irregular cycles and did not use hormone replacement therapy, but this was not significant on adjustment for all covariates. Having irregular menstrual cycles appears to be an early indicator for heart disease and diabetes. These findings suggest that irregular cycles among women in their forties may be linked to adverse cardio-metabolic outcomes. These women may benefit from screening and prevention strategies as recommended by related guidelines such as the international evidence-based guideline for the assessment and management of PCOS.

Abstract 9399: A Targeted Proteomic Approach Identifies Novel Biomarkers Associated With Risk of Myocardial Infarction in Post-Menopausal Women

Introduction: There may be unique pathways that contribute to heart disease in women. We used proteomics to evaluate the association between a panel of biomarkers and risk of incident MI in post-menopausal women and thus to inform risk prediction and potential disease biology. Methods: We analyzed 184 candidate biomarkers (Olink CVD II/III) in LOFT, a randomized trial of an osteoporosis drug in post-menopausal women. Cases and controls without prevalent CV disease were matched by age and follow-up time (123 MI cases, 123 controls). A Benjamini-Hochberg correction was applied for false discovery (adj P value <0.05). Conditional logistic regression was adjusted for the ACC/AHA pooled cohort equations (PCE). Results: 16 biomarkers assessed at baseline were associated with incident MI at the FDR threshold (Fig). After multivariable adjustment, 8 markers remained significantly associated with incident MI, including BNP (adj OR per SD 2.52, 95% CI 1.49-4.28), NT-proBNP (adj OR 2.41, 95% CI 1.43-4.08) and metalloproteinases including MMP-2 (adj OR 1.86, 95% CI 1.08-3.22) and MMP-12 (adj OR 1.55, 95% CI 1.02-2.37; Fig). Network analyses suggested these markers were overall strongly concentrated in pathways of inflammation, cellular movement and immune cell trafficking. Conclusions: A targeted proteomic approach identified markers of inflammation and immune cell trafficking as predictors of MI in post-menopausal women independent of traditional risk markers. Metalloproteinases, markers of plaque rupture and erosion, may provide insights into plaque biology and atherogenesis in women and warrant further investigation.

Cardiac and Obstetric Outcomes Associated With Mitral Valve Prolapse

Mitral valve prolapse (MVP) is the most common valvular heart disease in women of reproductive age. Whether MVP increases the likelihood of adverse outcomes in pregnancy is unknown. The study objective was to examine the cardiac and obstetric outcomes associated with MVP in pregnant women. This retrospective cohort study, using the Healthcare Cost and Utilization Project National Readmission Sample database between 2010 and 2017, identified all pregnant women with MVP using the International Classification of Disease, Ninth and Tenth Revisions codes. The maternal cardiac and obstetric outcomes in pregnant women diagnosed with MVP were compared with women without MVP using multivariable logistic and Cox proportional hazard regression models adjusted for baseline demographic characteristics. There were 23,000 pregnancy admissions with MVP with an overall incidence of 16.9 cases per 10,000 pregnancy admissions. Pregnant women with MVP were more likely to die during pregnancy (adjusted hazard ratio 5.13, 95% confidence interval [CI] 1.09 to 24.16), develop cardiac arrest (adjusted odds ratio [aOR] 4.44, 95% CI 1.04 to 18.89), arrhythmia (aOR 10.96, 95% CI 9.17 to 13.12), stroke (aOR 6.90, 95% CI 1.26 to 37.58), heart failure (aOR 5.81, 95% CI 3.84 to 8.79), or suffer a coronary artery dissection (aOR 25.22, 95% CI 3.42 to 186.07) compared with women without MVP. Pregnancies with MVP were also associated with increased risks of preterm delivery (aOR 1.21, 95% CI 1.02 to 1.44) and preeclampsia/hemolysis, elevated liver enzymes, and low platelets syndrome (aOR 1.22, 95% CI 1.05 to 1.41). In conclusion, MVP in pregnancy is associated with adverse maternal cardiac outcomes and higher obstetric risks.

The association between general and central obesity and the risks of coronary heart disease in women with and without a familial predisposition to obesity: findings from the Danish Nurse Cohort.

Several studies show an increased risk of coronary heart disease (CHD) among people with obesity, but it is largely unknown whether this association also depends on a familial predisposition to obesity. This study examined if associations between Body Mass Index (BMI) or waist circumference (WC) and incident CHD differed among Danish female nurses with and without familial overweight and obesity. Analyses were based on data from the Danish Nurse Cohort (n = 20,701). Self-reported height, weight and self-measured WC were assessed in 1999, as was information on familial overweight/obesity, defined as having one or both parents with overweight/obesity. Information on the development of or death from CHD was collected from nationwide Danish registries in 2015. Analyses were based on Cox proportional hazard regression models adjusted for potential confounding factors. Both BMI and WC were directly associated with CHD risk, but we found no evidence of effect modification from familial predisposition to obesity. Hence a familial predisposition to obesity does not seem to influence the risk of CHD associated with general or central obesity.

Heart Disease in Women

All women face the threat of heart disease. Knowing the symptoms and risks unique to women, as well as eating a hearthealthy diet and exercising, can help protect you. Heart disease is often thought to be more of a problem for men. However, it’s the most common cause of death for both women and men in the United States. Because some heart disease symptoms in women can differ f Heart attack symptoms for women. The most common heart attack symptom in women is the same as in men some type of chest pain, pressure or discomfort that lasts more than a few minutes or comes and goes. But chest pain is not always severe or even the most noticeable symptom, particularly in women. Women often describe it as pressure or tightness. And, it’s possible to have a heart attack without chest pain. Women are more likely than men to have heart attack symptoms unrelated to chest pain, such as: Neck, jaw, shoulder, upper back or abdominal discomfort, Shortness of breath, Pain in one or both arms, Nausea or vomiting, Sweating, Lightheadedness or dizziness, unusual fatigue, Indigestion. These symptoms may be vague and not as noticeable as the crushing chest pain often associated with heart attacks. This might be because women tend to have blockages not only in their main arteries but also in the smaller ones that supply blood to the heart-a condition called small vessel heart disease or coronary microvascular disease. Women tend to have symptoms more often when resting, or even when asleep, than they do in men. Emotional stress can play a role in triggering heart attack symptoms in women. Because women don’t always recognize their symptoms as those of a heart attack, they tend to show up in emergency rooms after heart damage has occurred. Also, because their symptoms often differ from men’s, women might be diagnosed less often with heart disease than men are. If you have symptoms of a heart attack or think you’re having one, call for emergency medical help immediately. Don’t drive yourself to the emergency room unless you have no other options. Rom those in men, women often don’t know what to look for

Interpersonal violence: Serious sequelae for heart disease in women.

Experiencing various forms of violence in either childhood or adulthood has been associated with cardiovascular disease, both shortly after the event and during follow-up, particularly in women. The coronavirus disease 2019 pandemic has heightened the risk of domestic violence with serious sequelae for mental and cardiovascular health in women, possibly due to several contributing factors, ranging from lockdown, stay at home regulations, job losses, anxiety, and stress. Accordingly, it remains paramount to enforce proactive preventive strategies, at both the family and individual level, maintain a high level of attention to recognize all forms of violence or abuse, and guarantee a multidisciplinary team approach for victims of interpersonal or domestic violence in order to address physical, sexual, and emotional domains and offer a personalized care.

Glucocorticoid Inhibition of Estrogen Regulation of the Serotonin Receptor 2B in Cardiomyocytes Exacerbates Cell Death in Hypoxia/Reoxygenation Injury.

BackgroundStress has emerged as an important risk factor for heart disease in women. Stress levels have been shown to correlate with delayed recovery and increased mortality after a myocardial infarction. Therefore, we sought to investigate if the observed sex‐specific effects of stress in myocardial infarction may be partly attributed to genomic interactions between the female sex hormones, estrogen (E2), and the primary stress hormones glucocorticoids.Methods and ResultsGenomewide studies show that glucocorticoids inhibit estrogen‐mediated regulation of genes with established roles in cardiomyocyte homeostasis. These include 5‐HT2BR (cardiac serotonin receptor 2B), the expression of which is critical to prevent cardiomyocyte death in the adult heart. Using siRNA, gene expression, and chromatin immunoprecipitation assays, we found that 5‐HT2BR is a primary target of the glucocorticoid receptor and the estrogen receptor α at the level of transcription. The glucocorticoid receptor blocks the recruitment of estrogen receptor α to the promoter of the 5‐HT2BR gene, which may contribute to the adverse effects of stress in the heart of premenopausal women. Using immunoblotting, TUNEL (terminal deoxynucleotidal transferase–mediated biotin–deoxyuridine triphosphate nick‐end labeling), and flow cytometry, we demonstrate that estrogen decreases cardiomyocyte death by a mechanism relying on 5‐HT2BR expression. In vitro and in vivo experiments show that glucocorticoids inhibit estrogen cardioprotection in response to hypoxia/reoxygenation injury and exacerbate the size of the infarct areas in myocardial infarction.ConclusionsThese results established a novel mechanism underlying the deleterious effects of stress on female cardiac health in the setting of ischemia/reperfusion.

The importance of stratifying ischemic risk by using the Duke score in women with ischemic heart disease and hypothyroidism before inclusion in cardiovascular rehabilitation programs

Introduction: The relationship between abnormal thyroid function and coronary heart disease has been known for a long time, and particularly, hypothyroidism is associated with an increased risk of cardiovascular disease. The aim of this study was to evaluate the ischemic risk by using the Duke score in women with ischemic heart disease and associated hypothyroidism before inclusion in cardiovascular rehabilitation program. Materials and methods: We included in the study 150 female patients admitted to the Cardiology Department of the Clinical Rehabilitation Hospital Cluj-Napoca. All the patients included had ischemic heart disease and performed an exercise stress testing to evaluate the effort capacity and also to stratify the ischemic risk by calculating the Duke Score. After dosing the thyroid stimulating hormone (TSH) we divided the patients in two groups: with hypothyroidism and a control group. Results: Patients with hypothyroidism were more frequently hypertensive, (98% vs 87%, p-0.035), and they had diabetes mellitus in a higher proportion (51% vs 22%, p-0.005). HDL cholesterol was significantly decreased in the group of patients with hypothyroidism: 40.36±10.39mg/dl vs 44.85±10.29mg/dl (p-0.01). Regarding the ischemic risk assessed by the Duke score, the statistically significant differences between the two groups were registered only for the category of high-risk patients, 5.55% vs 18% (p-0.048). Also, the TSH value was higher in the group with high-risk Duke score, 4.21±3.73µIU/ml, compared to the moderate-risk score group, 1.95±1.12µIU/ml(p-0.05). Conclusion: In women with ischemic heart disease, assessing thyroid function can be useful to identify patients at high risk of ischemia. Patients with hypothyroidism tend to have a higher prevalence of cardiovascular risk factors, a higher ischemic risk objectified by the Duke score and more commonly multivascular coronary lesions. For these patients, the inclusion in cardiovascular rehabilitation programs is essential, but it is very important that the programs to be customized for each patient. Keywords: coronary heart disease in women, exercise ECG, Duke score, ischemic risk, hypothyroidism, cardiovascular rehabilitation programs

Association of blood pressure and coronary heart disease in women of an open population of a moderately urbanized city of Western Siberia

Objective. The aim of this study was to assess the association between the level of blood pressure (BP) and the prevalence of coronary heart disease (CHD) in women of working age in an open population of a moderately urbanized Siberian city (on the model of Tyumen).Design and methods. We included 1000 women of an open urban population aged 25–64 years, 250 people in each of four decades of life (among persons 25–34, 35–44, 45–54, 55–-64 years old), selected by the method of a random representative sample from the electoral lists of the administrative district of Tyumen, the response was 70,3% (703 participants). In all subjects we measured BP; assessed the presence of coronary artery disease — according to standardized epidemiological methods: based on the extended criteria, “definite” CHD (strict criteria) and “possible” CHD (non-strict criteria) were distinguished. Statistical analysis was performed using STATISTICA 12.0 software, the differences were considered significant at p-level ≤ 0,005.Results. Almost every third woman (25–64 years old) had increased BP (34,7 %), the frequency of increased BP grows with age, reaching 63,3 % in the older group. Low awareness of high BP and low adherence to treatment were found. There was a correlation between the prevalence of CHD and BP level and age. In the presence of increased systolic BP, the chance of developing CHD in women aged 25–64 years in the open population increases by 1,9–2,7 times (p < 0,05), in the presence of increased diastolic BP, the chance of developing CHD according to extended criteria increases by 2,1 times (odds ratio = 2,08, 95 % confidence interval (1,15; 3,74)).Conclusions. Our results can be used for improving the strategy of primary cardiovascular prevention in preventive programs of the Western Siberia region.

Managing Ischemic Heart Disease in Women: Role of a Women's Heart Center.

Purpose of ReviewHeart centers for women (HCW) were developed due to the rising cardiovascular morbidity and mortality in women in the United States in the early 1990s. Our review encompasses the epidemiology, risk factors, diagnostic strategies, treatments, and the role of HCW in managing women with ischemic heart disease (IHD).Recent FindingsHCW use a multidisciplinary team to manage women with IHD. Due to the paucity of randomized controlled trials investigating various manifestations of IHD, some treatments are not evidence-based such as those for coronary microvascular dysfunction and spontaneous coronary artery dissection. Sex-specific risk factors have been identified and multimodality cardiac imaging is improving in diagnosing IHD in women. Treatments are being studied to help improve symptoms and outcomes in women with IHD.SummaryThere has been progress in the care of women with IHD. HCW can be instrumental in treating women with IHD, doing research, and being a source of research study participants.

Women and Cardiac Disease: A Special Issue

Cardiovascular disease is the leading cause of death in women worldwide. Despite improvements in awareness on heart disease in women through various campaigns and initiatives, cardiovascular risk in women still tends to be underestimated by health care professionals and women themselves. With respect to the latter, a study from the United States has even shown a decline in awareness regarding the fact that heart disease is the leading cause of death among women over recent years. Especially young women are [...]

How the Gender Gap Affects the Incidence and Prognosis of Cardiovascular Disease

The study in this issue of the Journal analyzed the sex and gender gap that exists for ischemic heart disease and myocardial infarction. The authors reviewed all the factors that differ between genders in terms of incidence, mortality, pathophysiology and clinical implications, diagnosis, and treatment. The article highlights firstly that there has been an increase in the annual change in proportional mortality from ischemic heart disease in women in recent years, with an age-standardized incidence of 104 per 100 000 [...]

An incidence of ischemic heart disease in women of South India

Background: Ischemic heart disease also known as Coronary artery disease is a most common condition in Indian population which allows inadequate supply of blood and oxygen to a portion of the myocardium. It stands as one of the primary causes of death in both men and women and hence need for clinical investigation of IHD in our population is important. Aim: The study is designed to know the clinical profile of female participants attending tertiary care hospital in south India. Materials and Methods: All participants included in the study are symptomatic to IHD and biochemical and electrocardiogram was performed to screen the participants and participant’s history is collected. Results: A total of 140 participants were considered for the study and 120 were identified as IHD positive. Mean age of participants was 55 and most of the incumbents reported chest pain as the major complication followed by other complications like hypertension and diabetes. Conclusion: The incidence of IHD is found to be highest in 53-57 year age group with diabetes, hypertension and Dyslipidaemia as the major risk factors. Lack of awareness in participants also delayed them in their arrival to hospital. Hence there is an immediate need to conduct awareness campaigns in rural areas of our democratic country.

Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD), including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion; however, this therapeutic approach leads to ischemic/reperfusion injury (IRI), often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

Preventing Heart Disease in Women: New Guidance from the American Heart Association

Sponsoring Organization: American Heart Association (AHA)Background and ObjectiveAs cardiovascular disease (CVD) remains the leading cause of death

Heart disease in women: a narrative review.

Cardiovascular disease is the worldwide leading cause of death in women. Biological differences between the sexes, a result of genetic, epigenetic and sex hormone-mediated factors, are complex and incompletely understood. These differences are compounded by socio-cultural factors and together account for the variation in the prevalence, presentation and natural history of cardiovascular disease between men and women. Although there is growing recognition of sex-specific determinants of outcomes, women remain under-represented in clinical trials, and sex-disaggregated diagnostic and management strategies are not currently recommended in clinical guidelines. Women remain more likely to experience delays in diagnosis, to be treated less aggressively and to have worse outcomes. As a consequence, cardiovascular disease in women remains understudied, underdiagnosed and undertreated. This review will focus on female-specific characteristics of cardiovascular disease and how these may impact on anaesthetic and peri-operative risk assessment and care. We highlight significant differences between the sexes in the natural history of cardiovascular disease, including those disease entities that are more common in women, such as sudden coronary artery dissection or microvascular dysfunction. Given the rapidly rising incidence of maternal cardiovascular disease and associated complications, special consideration is given to the risk assessment and management of these conditions during pregnancy. Increased awareness of these issues has the potential to improve the effectiveness of the multidisciplinary heart team and ultimately improve the care provided to women.

Go Red for Women Strategically Focused Research Network: Summary of Findings and Network Outcomes.

The Go Red for Women movement was initiated by the American Heart Association (AHA) in the early 2000s to raise awareness concerning cardiovascular disease (CVD) risk in women. In 2016, the AHA funded 5 research centers across the United States to advance our knowledge of the risks and presentation of CVD that are specific to women. This report highlights the findings of the centers, showing how insufficient sleep, sedentariness, and pregnancy‐related complications may increase CVD risk in women, as well as presentation and factors associated with myocardial infarction with nonobstructive coronary arteries and heart failure with preserved ejection fraction in women. These projects were augmented by collaborative ancillary studies assessing the relationships between various lifestyle behaviors, including nightly fasting duration, mindfulness, and behavioral and anthropometric risk factors and CVD risk, as well as metabolomic profiling of heart failure with preserved ejection fraction in women. The Go Red for Women Strategically Focused Research Network enhanced the evidence base related to heart disease in women, promoting awareness of the female‐specific factors that influence CVD.

Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women

Risk profiles for premature coronary heart disease (CHD) are unclear. To examine baseline risk profiles for incident CHD in women by age at onset. A prospective cohort of US female health professionals participating in the Women's Health Study was conducted; median follow-up was 21.4 years. Participants included 28 024 women aged 45 years or older without known cardiovascular disease. Baseline profiles were obtained from April 30, 1993, to January 24, 1996, and analyses were conducted from October 1, 2017, to October 1, 2020. More than 50 clinical, lipid, inflammatory, and metabolic risk factors and biomarkers. Four age groups were examined (<55, 55 to <65, 65 to <75, and ≥75 years) for CHD onset, and adjusted hazard ratios (aHRs) were calculated using stratified Cox proportional hazard regression models with age as the time scale and adjusting for clinical factors. Women contributed to different age groups over time. Of the clinical factors in the women, diabetes had the highest aHR for CHD onset at any age, ranging from 10.71 (95% CI, 5.57-20.60) at CHD onset in those younger than 55 years to 3.47 (95% CI, 2.47-4.87) at CHD onset in those 75 years or older. Risks that were also noted for CHD onset in participants younger than 55 years included metabolic syndrome (aHR, 6.09; 95% CI, 3.60-10.29), hypertension (aHR, 4.58; 95% CI, 2.76-7.60), obesity (aHR, 4.33; 95% CI, 2.31-8.11), and smoking (aHR, 3.92; 95% CI, 2.32-6.63). Myocardial infarction in a parent before age 60 years was associated with 1.5- to 2-fold risk of CHD in participants up to age 75 years. From approximately 50 biomarkers, lipoprotein insulin resistance had the highest standardized aHR: 6.40 (95% CI, 3.14-13.06) for CHD onset in women younger than 55 years, attenuating with age. In comparison, weaker but significant associations with CHD in women younger than 55 years were noted (per SD increment) for low-density lipoprotein cholesterol (aHR, 1.38; 95% CI, 1.10-1.74), non-high-density lipoprotein cholesterol (aHR, 1.67; 95% CI, 1.36-2.04), apolipoprotein B (aHR, 1.89; 95% CI, 1.52-2.35), triglycerides (aHR, 2.14; 95% CI, 1.72-2.67), and inflammatory biomarkers (1.2- to 1.8-fold)-all attenuating with age. Some biomarkers had similar CHD age associations (eg, physical inactivity, lipoprotein[a], total high-density lipoprotein particles), while a few had no association with CHD onset at any age. Most risk factors and biomarkers had associations that attenuated with increasing age at onset. In this cohort study, diabetes and insulin resistance, in addition to hypertension, obesity, and smoking, appeared to be the strongest risk factors for premature onset of CHD. Most risk factors had attenuated relative rates at older ages.