Impact of Postoperative Radiotherapy on the Risk of Ischemic Heart Disease and Survival in Patients with Ductal Carcinoma In Situ: A Nationwide Claims-Based Cohort Study.

Background:Adjuvant radiotherapy (RT) for breast cancer (BC) substantially reduces BC mortality and loco-regional recurrences, but incidental radiation exposure to the heart is associated with ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC. Patients and methods: The Breast Cancer DataBase Sweden (BCBase) cohort includes all women diagnosed with BC in three of Sweden's six health care regions from 1992-2012 with five age-matched controls without a history of BC for each BC case. A total of 60217 women with BC were included in the BC cohort, and 300791 women without BC in the comparison cohort. Through linkage with a number of population-based registries, information concerning comorbidity, socioeconomic status, and incidence of IHD was obtained. Cox proportional hazards regression analyses were performed to estimate risk of IHD for women with BC compared to the comparison cohort, and for women with left-sided BC compared to right-sided BC. The analyses were adjusted for previous IHD, comorbidity, and socioeconomic status. The BC cohort was stratified by RT, endocrine therapy, and chemotherapy. Results: The median follow-up time was 8.1 years. The risk of IHD was significantly lower for the BC cohort compared to the comparison cohort, with a hazard ratio (HR) of 0.91 (95% CI 0.88-0.95). The HR's for IHD was even lower in women with BC selected for adjuvant treatment with RT, endocrine therapy or chemotherapy. When women with left-sided BC were compared to right-sided BC an increased HR for IHD of 1.09 (95% CI 1.01-1.17) was seen for the whole cohort, and of 1.18 (95% CI 1.06-1.31) in women receiving RT. When RT was stratified for pathological nodal involvement, a HR of 1.22 (95% CI 0.98-1.51) for women with 1 to 3 pathological lymph nodes was seen, and of 1.72 (95% CI 1.19-2.48) for women with more than 4 pathological lymph nodes, probably reflecting more extensive RT. When RT was combined with other adjuvant treatments, a HR for IHD of 1.24 (95% CI 1.09-1.42) was seen for endocrine therapy, of 1.28 (95% CI 0.98-1.67) for chemotherapy, and of 1.35 (95% CI 0.95-1.92) for endocrine therapy and chemotherapy combined in left-sided BC compared to right-sided BC, suggesting an additive effect to RT on the risk of IHD. Conclusion: The results show a persisting increase in risk of IHD in left-sided RT with contemporary radiation techniques and radiation targets. The increase in risk of IHD in women with left-sided RT seen when endocrine therapy and chemotherapy were added to RT suggests an additive effect on the risk of radiation-induced IHD. Long-term side effects of adjuvant treatment have to be taken into consideration in RT planning to ensure health and quality of life for BC survivors. The results are an incentive to conduct further research concerning dose constraints to the coronary arteries, and of implementation of RT techniques that can lower cardiac radiation doses. Selection of patients to active treatment, and a healthier lifestyle in BC survivors may explain the findings of lower risk of IHD in the BC cohort compared to the comparison cohort. Citation Format: Wennstig A-K, Wadsten C, Garmo H, Wärnberg F, Holmberg L, Blomqvist C, Nilsson G, Sund M. Risk of ischemic heart disease after adjuvant radiotherapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-01.

PurposeThe use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS.MethodsThe Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992–2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed.ResultsMedian follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82–1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60–0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53–1.37 for left-sided versus right-sided RT).ConclusionsThe risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.

In recent decades, there has been an appropriate focus on ensuring gender equity in the quantity and quality of evidence to guide female-specific, optimal management strategies for suspected and known ischemic heart disease (IHD). The evolving evidence supports a multifactorial pathophysiology of coronary atherosclerosis that includes obstructive coronary artery disease (CAD) and dysfunction of the coronary microvasculature and endothelium, and therefore, the term IHD best encompasses this varied pathophysiology in women. An overwhelming body of evidence has documented undertreatment and undertesting of women, leading to higher case fatality rates and increased morbid complications among women.1–3 Accordingly, to increase our knowledge base, women were given the status of a priority population, which resulted in federal policy to include proportional representation of females in clinical trials and registries.4 The past decade provided abundant evidence to guide clinical decision making regarding diagnostic testing for suspected IHD. In 2005, the American Heart Association (AHA) published an evidence synthesis on the use of CAD imaging for the evaluation of symptomatic women with suspected myocardial ischemia.5 Numerous reports have since provided additional high-quality evidence, including data on coronary computed tomographic angiography (CCTA) and cardiac magnetic resonance imaging (CMR), which in 2005 were considered research techniques.5 The present statement provides an update to the 2005 document and synthesizes contemporary evidence on appropriate symptomatic female candidates for diagnostic testing, as well as sex-specific data on the diagnostic and prognostic accuracy for exercise treadmill testing (ETT) with electrocardiography, stress echocardiography, stress myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) or positron emission tomography (PET), stress CMR, and CCTA.5 Within this document, quality evidence is synthesized, and important gaps in knowledge about the assessment of IHD risk in women are identified. The 2005 document included sections on the evaluation of asymptomatic …

Hepatic lipase mutations,elevated high-density lipoprotein cholesterol, and increased risk of ischemic heart disease: The Copenhagen City Heart Study

To investigate the interplay between use of alcohol, concentration of low density lipoprotein cholesterol, and risk of ischaemic heart disease. Prospective study with controlling for several relevant confounders, including concentrations of other lipid fractions. Copenhagen male study, Denmark. 2826 men aged 53-74 years without overt ischaemic heart disease. Incidence of ischaemic heart disease during a six year follow up period. 172 men (6.1%) had a first ischaemic heart disease event. There was an overall inverse association between alcohol intake and risk of ischaemic heart disease. The association was highly dependent on concentration of low density lipoprotein cholesterol. In men with a high concentration (> or = 5.25 mmol/l) cumulative incidence rates of ischaemic heart disease were 16.4% for abstainers, 8.7% for those who drank 1-21 beverages a week, and 4.4% for those who drank 22 or more beverages a week. With abstainers as reference and after adjustment for confounders, corresponding relative risks (95% confidence interval) were 0.4 (0.2 to 1.0; P<0.05) and 0.2 (0.1 to 0.8; P<0.01). In men with a concentration <3.63 mmol/l use of alcohol was not associated with risk. The attributable risk (95% confidence interval) of ischaemic heart disease among men with concentrations > or = 3.63 mmol/l who abstained from drinking alcohol was 43% (10% to 64%). In middle aged and elderly men the inverse association between alcohol consumption and risk of ischaemic heart disease is highly dependent on the concentration of low density lipoprotein cholesterol. These results support the suggestion that use of alcohol may in part explain the French paradox.

To demonstrate the prevalence of sonographic fatty liver, overweight and ischemic heart disease (IHD) among the male workers in Taiwan, and to investigate the possible association of these three factors. From July to September 2003, a total of 2 088 male aircraft-maintenance workers aged from 22 to 65 years (mean 40.5) underwent an annual health examination, including anthropometrical evaluation, blood pressure measurement, personal medical history assessment, biochemical blood analysis, abdominal ultrasonographic examination and digital electrocardiography (ECG). The Student's t-test, chi(2) test and multivariate logistic regression analysis were utilized to evaluate the relationship between IHD and salient risk factors. The all-over prevalence of overweight was 41.4%, and that of fatty liver was 29.5% (mild, moderate and severe fatty liver being 14.5%, 11.3%, and 3.7%, respectively); while the prevalence of ischemic changes on ECG was 17.1% in this study. The abnormal rates for conventional IHD risk factors including hypertension, dyslipidemia, hyperglycemia and overweight increased in accordance with the severity of fatty liver. Overweight and severity of fatty liver were independently associated with increased risks for developing IHD. Overweight subjects had a 1.32-fold (95%CI: 1.01-1.73) increased IHD risk. Participants with mild, moderate, and severe fatty liver had a 1.88-fold (95%CI: 1.37-2.6), 2.37-fold (95%CI: 1.66-3.37) and 2.76-fold (95%CI: 1.62-4.72) increased risk for developing IHD. The prevalence of ischemic ECG for the fatty liver-affected subjects with or without overweight was 30.1% and 19.1%, while that of overweight subjects free from fatty liver was 14.4%. Compared to the subjects without fatty liver nor overweight, IHD risk for the three subgroups above was as follows: OR: 2.95 (95%CI: 2.31-4.09), OR: 1.60 (95%CI: 1.07-2.39) and OR: 1.11 (95%CI: 0.78-1.56), respectively. The presence of fatty liver and its severity should be carefully considered as independent risk factors for IHD. Results of the study suggest the synergistic effect between fatty liver and overweight for developing IHD. Abdominal sonographic examination may provide valuable information for IHD risk assessment in addition to limited report about liver status, especially for overweight males.

Despite the importance of comorbid ischemic heart disease (IHD) in the prognosis of asthma, the long-term impact of coronavirus disease 2019 (COVID-19) on IHD in adults with asthma remains unclear. This study investigated the long-term effects of COVID-19 on the risk of IHD in individuals with asthma, particularly regarding COVID-19 severity. Using the Korean National Health Insurance Service claims database, we identified individuals with asthma who had recovered from COVID-19 between October 8, 2020, and December 31, 2021 (n = 8,011) and 1:1 propensity score-matched controls (n = 8,011). The incidence and risk of IHD were compared between the two groups. Overall, during a median follow-up of 95 days (interquartile range, 34–213 days; range, 1–448 days), which includes a median of 14 lag days, the COVID-19 cohort did not show a higher risk of IHD (hazard ratio [HR], 2.11; 95% confidence interval [CI], 0.99–4.48) compared to matched controls. However, when the severity of COVID-19 was considered, the severe COVID-19 cohort exhibited a higher risk of IHD (HR, 4.89; 95% CI, 1.86–12.84) than matched controls; in contrast, the non-severe COVID-19 cohort showed no significantly increased risk of IHD (HR, 1.64; 95% CI, 0.73–3.70). Severe COVID-19 is associated with an increased long-term risk of IHD in adults with asthma, emphasizing the importance of cardiovascular events monitoring to improve asthma treatment outcomes in the era of COVID-19.

The chaperoning system, which is responsible for protein homeostasis, plays a significant role in cardiovascular diseases. Among molecular chaperones or heat shock proteins (HSPs), the HSP40 family, the main co-chaperone of HSP70, remains largely underexplored, especially in ischemic heart disease (IHD) risk. We genotyped 834 IHD patients and 1,328 healthy controls for three SNPs (rs2034598 and rs7189628 DNAJA2 and rs4926222 DNAJB1) using probe-based real-time PCR. We observed that SNP rs7189628 DNAJA2 was associated with increased IHD risk in smokers (effect allele [EA] T, OR = 1.65, 95%CI 1.01-2.71, p = 0.036), while SNP rs2034598 DNAJA2 was associated with increased IHD risk in non-smokers (EA A, OR = 1.22, 95%CI 1.02-1.47, p = 0.036). Oppositely, SNP rs4926222 DNAJB1 was associated with reduced IHD risk in patients under 62 years old (EA G, OR = 0.73, 95%CI 0.54-0.98, p = 0.02). These SNPs also modulated clinical parameters: rs7189628 was associated with higher platelet counts in the entire group (p = 0.03) and males (p = 0.02), while rs2034598 was associated with lower platelet counts in the same groups accordingly (p = 0.03 and p = 0.047), earlier IHD onset in males (p = 0.03), and reduced activated partial thromboplastin time in smokers (p = 0.01); rs4926222 DNAJB1 was Linked to elevated prothrombin index in patients aged 62 and higher (p = 0.04) and lower BMI in smokers (p = 0.005) and males (p = 0.02). Our findings suggest that genetic variants in the HSP40 family influence IHD risk and clinical features in a context-specific manner.

We assessed the relationship between psychological stress and ischaemic heart disease (IHD) incidence in a population of 868 men over a 10-year follow-up period. In 1981, 869 men aged 42-60, free from IHD and living around Quebec City completed a questionnaire assessing the presence of psychological stress in different areas of their life. They also underwent a medical examination and provided information on IHD risk factors. From 1981 to 1991, the incidence of IHD events was ascertained. The relationship between 13 stress dimensions and IHD incidence was investigated using Cox regression while controlling for important IHD risk factors. Cross-sectional analyses were also performed to investigate the relationship between stress dimensions and IHD risk factors. Between 1981 and 1991, 79 men (9%) experienced a first IHD event. The following risk factors were associated with the risk of IHD: age, (rate ratio (RR) = 1.93, 95% CI: 1.21-3.09), hypertension (RR = 1.90, 95% CI: 1.22-2.98), triglycerides (RR = 1.87, 95% CI: 1.19-2.95) and high density lipoprotein (HDL) cholesterol (RR = 1.64, 95% CI: 1.05-2.55). After controlling for risk factors, not one of the psychological stress dimensions significantly altered the risk of IHD. While confirming the influence of hypertension, age, triglycerides and HDL cholesterol on IHD incidence, this study suggests that there is no important connection between the explored stress dimensions and IHD incidence. It is unlikely that this lack of association is due to the stress questionnaire since the 13 stress dimensions were rigorously developed through independent evaluation of the questions by three specialists and many statistically significant relationships were observed between stress dimensions and IHD risk factors.

Background and aim: Green living environments are associated with beneficial health outcomes, whereas higher air pollution exposure might increase the risk of chronic diseases. Moreover, few studies have explored the interaction between residential greenness and air pollution on the risk of ischemic heart disease (IHD). Therefore we aimed to estimate the associations of residential greenness and air pollution with IHD and their interaction. Methods: We performed a prospective cohort study that included 29,141 adult participants recruited from Yinzhou District, Ningbo, China. Normalized Difference Vegetation Index (NDVI) around each participant’s residence was calculated to measure residential greenness exposure. Land-use regression models were conducted to estimate long-term individual exposure to air pollutants, including nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters &amp;#x2264; 2.5 &amp;#x3bc;m (PM2.5) and &amp;#x2264;10 &amp;#x3bc;m (PM10). Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of residential greenness and air pollutants with the risk of incident IHD. Results: During 101,172.5 person-years of follow-up, 1,392 incident IHD cases were reported in the study population. Residential greenness, expressed as an interquartile range (IQR) increase in NDVI within 300m, was inversely associated with incident IHD. However, long-term air pollution exposures were associated with higher IHD incidence. Mediation analyses suggested that the beneficial effect of residential greenness on incident IHD could be partly mediated by reducing the exposure to PM2.5. Conclusion: Higher greenness was associated with decreased risk of IHD, while air pollutants were positively associated with incident IHD. Meanwhile, residential greenness may decrease the risk of IHD by reducing PM2.5 exposure. Keywords: Residential greenness; Air pollution; Ischemic heart disease; Cohort study; Effect mediation

Posttraumatic stress disorder (PTSD) is associated with greater risk of ischemic heart disease (IHD) in predominantly male populations or limited community samples. Women veterans represent a growing, yet understudied, population with high levels of trauma exposure and unique cardiovascular risks, but research on PTSD and IHD in this group is lacking. To determine whether PTSD is associated with incident IHD in women veterans. In this retrospective, longitudinal cohort study of the national Veterans Health Administration (VHA) electronic medical records, the a priori hypothesis that PTSD would be associated with greater risk of IHD onset was tested. Women veterans 18 years or older with and without PTSD who were patients in the VHA from January 1, 2000, to December 31, 2017, were assessed for study eligibility. Exclusion criteria consisted of no VHA clinical encounters after the index visit, IHD diagnosis at or before the index visit, and IHD diagnosis within 90 days of the index visit. Propensity score matching on age at index visit, number of prior visits, and presence of traditional and female-specific cardiovascular risk factors and mental and physical health conditions was conducted to identify women veterans ever diagnosed with PTSD, who were matched in a 1:2 ratio to those never diagnosed with PTSD. Data were analyzed from October 1, 2018, to October 30, 2020. PTSD, defined by International Classification of Diseases, Ninth Revision (ICD-9), or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), diagnosis codes from inpatient or outpatient encounters. Incident IHD, defined as new-onset coronary artery disease, angina, or myocardial infarction, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient encounters, and/or coronary interventions based on Current Procedural Terminology codes. A total of 398 769 women veterans, 132 923 with PTSD and 265 846 never diagnosed with PTSD, were included in the analysis. Baseline mean (SD) age was 40.1 (12.2) years. During median follow-up of 4.9 (interquartile range, 2.1-9.2) years, 4381 women with PTSD (3.3%) and 5559 control individuals (2.1%) developed incident IHD. In a Cox proportional hazards model, PTSD was significantly associated with greater risk of developing IHD (hazard ratio [HR], 1.44; 95% CI, 1.38-1.50). Secondary stratified analyses indicated that younger age identified women veterans with PTSD who were at greater risk of incident IHD. Effect sizes were largest for those younger than 40 years at baseline (HR, 1.72; 95% CI, 1.55-1.93) and decreased monotonically with increasing age (HR for ≥60 years, 1.24; 95% CI, 1.12-1.38). This cohort study found that PTSD was associated with increased risk of IHD in women veterans and may have implications for IHD risk assessment in vulnerable individuals.

Prevalence and incidence of ischemic heart disease in multiple sclerosis: A population-based validation study

Residential greenness, air pollution, and incident ischemic heart disease: A prospective cohort study in China.

Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta-analysis

Combined Exposure to Multiple Air Pollutants and Incident Ischemic Heart Disease in Individuals with and without Type 2 Diabetes: A Cohort Study from the UK Biobank