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Background: Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years., Methods: In the Women's Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors., Results: Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17-1.42)] but not with nonpremature CHD [1.09(0.98-1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52-2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20-1.45) and 1.22(1.10-1.35)] and C-reactive protein [1.34(1.19-1.50) and 1.25(1.08-1.44)]., Conclusions: In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: The extent to which the contribution of pregnancy loss to cardiovascular diseases (CVDs) can be explained by metabolic disorders is poorly elucidated but holds insights for reducing long-term cardiovascular risk. The aim of this study is to investigate the mediating effects of hypertension, diabetes mellitus (DM), and lipoprotein metabolism disorders on the association of miscarriage and stillbirth with coronary heart disease (CHD), stroke, heart failure, atrial fibrillation, and composite outcomes., Methods and Results: A total of 163 283 ever-gravid women (age 55.3 ± 7.9 years) from the UK Biobank cohort without established metabolic disorders and CVDs were included and followed from 2007 to 2010 baseline until December 2020. Causal mediation analyses were used to estimate the proportion mediated. Hypertension mediated 11.1% (95% confidence interval, 3.7-18.5%) of the association between a history of miscarriage and incident CHD. Approximately, 9.5% (4.1-14.8%) of the effect of recurrent miscarriages on incident CHD was via hypertension, 8.4% (2.5-14.3%) of the effect was via lipoprotein metabolism disorders, 1.7% (0.5-2.9%) of the effect was via DM, and 10.7% (0.2-21.1%) of the effect of recurrent miscarriages on incident stroke was via hypertension. Hypertension mediated the largest proportion of effect for the atherosclerotic cardiovascular event (15.5% for a history of miscarriage and 9.4% for recurrent miscarriages), followed by lipoprotein metabolism disorders and DM., Conclusion: Hypertension, DM, and lipoprotein metabolism disorders mediated the association between miscarriage and various cardiovascular outcomes in later life. In particular, hypertension mediated a large proportion of the relationship between miscarriage and atherosclerotic CVD., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults., Methods and Results: Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, there were 1235 global CVD events, 530 AF events, and 1173 deaths. Higher IL-6 [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.44-1.72 per log unit increase] and IL-18 (HR 1.13, 95% CI 1.01-1.26) were significantly associated with global CVD after adjustment for cardiovascular risk factors. Association between IL-6 and global CVD remained significant after further adjustment for high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT) but was no longer significant for IL-18 after further adjustments. Interleukin-6 was also associated with increased risk for CHD, HF, and AF after adjustment for covariates. Both IL-6 and IL-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers., Conclusion: Among older adults, both IL-6 and IL-18 were associated with global CVD and death. The association between IL-6 with CVD appears to be more robust and was independent of hs-CRP, NT-proBNP, and hs-TnT., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits., Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45-64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex., Results: Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex., Conclusions: In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate the association of (changes in) electrocardiogram (ECG) abnormalities with incident major adverse cardiac events (MACE) in people with Type 2 diabetes (T2D) without pre-existing cardiovascular disease (CVD)., Methods and Results: A prospective longitudinal study of 11 993 people with T2D without known CVD from the Hoorn Diabetes Care System cohort. Annually repeated measurements (1998-2018), included cardiovascular risk factors, over 70 000 ECG, and self-reported cardiovascular events. ECG abnormalities were classified according to the Minnesota Classification as prolonged PR duration, prolonged QRS duration, left QRS-axis, QS pattern, ST-segment/T-wave abnormalities, or tall R-wave. The association of ECG abnormalities with MACEs was assessed using time-dependent Cox-regression models, adjusted for time-varying cardiovascular risk factors, and medication use [hazard ratios (HRs) with 95% confidence intervals (CIs)]. During a median follow-up of 6.6 (IQR, 3.1-10.7) years, 5445 (45.4%) of the participants had an ECG abnormality (prevalent or incident) at any of the median 6 (IQR, 3-10) annual ECG recordings, and 905 people (7.5%) had a MACE (529 coronary heart disease (CHD), 250 heart failure (HF), and 126 sudden cardiac arrest (SCA)). After adjustment, most ECG abnormalities were associated with HF: prolonged QRS duration [HR, 4.01 (95% CI, 2.67-6.03)], QS pattern [2.68 (0.85-8.49)], ST-segment/T-wave abnormalities [4.26 (2.67-6.80)], and tall R-wave [2.23 (1.33-3.76)]. Only QS pattern [2.69 (1.20-6.03)] and ST-segment/T-wave abnormalities [2.11 (1.48-3.02)] were associated with CHD. These associations were robust across age, sex, hypertension, or estimated CVD risk subgroups., Conclusion: In people with T2D without pre-existing CVD, ECG abnormalities related to decelerated conduction, ischaemia, and hypertrophy are predominantly early signs of emerging HF, while only abnormalities related to ischaemic disorders are signs of CHD., Competing Interests: Conflicts of interest: The authors had complete autonomy in the design, conduct, and reporting of the manuscript. The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: This study explored the associations of genetic susceptibility and adherence to a healthy lifestyle with incident coronary heart disease (CHD) and stroke in individuals with hypertension., Methods and Results: This study included 258 531 European descendants with hypertension at baseline from UK Biobank. Genetic risk of CHD and stroke was estimated using polygenic risk scores derived from 300 and 87 single-nucleotide polymorphisms, respectively. Lifestyle scores were calculated based on 4 lifestyle components (no obesity, no current smoking, regular physical activity and healthy diet). Cox regression with age as the underlying timescale was fit for incident CHD (n = 7470) and stroke (n = 5015), separately. A favourable lifestyle (3-4 lifestyle components) was associated with 37% and 30% lower hazards of CHD (95% confidence intervals, 32-42%) and stroke (23-37%), compared with an unfavourable lifestyle (0-1 lifestyle component), at all levels of genetic risk. Evidence of interaction between genetic susceptibility and lifestyle adherence was found for stroke (P = 0.036): no evidence of interaction for CHD (P = 0.524). A favourable lifestyle at high genetic risk had lower 12-year absolute risk of CHD and stroke, compared with an unfavourable lifestyle at low-to-intermediate genetic (exception: an unfavourable lifestyle at low CHD genetic risk)., Conclusion: Adhering to a healthy lifestyle is associated with lower CHD and stroke risk regardless of genetic risk among individuals with hypertension. Risk of CHD and stroke for those at high genetic risk but adhering to a healthy lifestyle was generally lower than for those at low-to-intermediate genetic risk but adhering to an unhealthy lifestyle., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aims: This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors., Methods and Results: EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking. Prentice-weighted Cox regression was used to assess the association between physical activity and incident CHD events (non-fatal and fatal).Compared to inactive participants without the respective CHD risk factor (referent), excess CHD risk was highest in physically inactive and lowest in moderately active participants with CHD risk factors. Corresponding excess CHD risk estimates amongst those with obesity were 47% [95% confidence interval (CI) 32-64%] and 21% (95%CI 2-44%), with hypercholesterolaemia were 80% (95%CI 55-108%) and 48% (95%CI 22-81%), with hypertension were 80% (95%CI 65-96%) and 49% (95%CI 28-74%), with diabetes were 142% (95%CI 63-260%), and 100% (95%CI 32-204%), and amongst smokers were 152% (95%CI 122-186%) and 109% (95%CI 74-150%)., Conclusions: In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk., Competing Interests: Conflict of interest: All the authors have nothing relevant to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To evaluate the sex-specific predictive value of N-terminal pro B-type natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase myocardial band (CK-MB) for 10-year risk prediction of coronary heart disease (CHD), stroke, heart failure (HF) and composite outcomes., Methods: Five-thousand four-hundred thirty individuals (mean age 68.6 years, 59.9% women) from the Rotterdam Study, with biomarker measurements between 1997 and 2001, were included. Participants were followed until 2015. We fitted 'basic' models using traditional cardiovascular risk factors. Improvements in c-statistics and net reclassification improvement (NRI) for events and non-events were calculated., Results: During a median follow-up of 14 years, 747 (13.8%), 563 (10.4%), and 664 (12.2%) participants were diagnosed with CHD, stroke, and HF, respectively. NT-proBNP improved the discriminative performance of the 'basic' model for all endpoints (c-statistic improvements ranging from 0.007 to 0.050) and provided significant event-NRI for HF (14.3% in women; 10.7% in men) and for stroke in men (9.3%). The addition of hs-cTnT increased c-statistic for CHD in women by 0.029 (95% CI, 0.011-0.047) and for HF in men by 0.034 (95% CI, 0.014-0.053), and provided significant event-NRI for CHD (10.3%) and HF (7.8%) in women, and for stroke (8.4%) in men. The added predictive value of CK-MB was limited., Conclusion: NT-proBNP and hs-cTnT provided added predictive value for various cardiovascular outcomes above traditional risk factors. Sex differences were observed in the predictive performance of these biomarkers., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: In patients with coronary heart disease (CHD), we investigated whether it is possible to accurately assess the probability of short-term control of risk factors (blood pressure, cholesterol, smoking) based on individual and large-area residential characteristics., Methods and Results: We merged individual data of participants from EUROASPIRE V who were hospitalized for CHD (2014-2017) and interviewed and examined for risk factor control (2016-2017), with large-area residential data provided by Eurostat for Nomenclature of Territorial Units for Statistics (NUTS) regions using postal codes. Data from 2562 CHD patients in 16 countries were linked to data from 60 NUTS 2 and 121 NUTS 3 regions. The median time between hospitalization and interview was 14 months. We developed prediction models to assess the probability of risk factor control at interview using data from the time of hospitalization: (i) baseline models including 35 variables on patients' demographic, clinical, and socio-economic characteristics and (ii) extended models additionally considering nine variables on large-area residential characteristics. We calculated and internally validated c-indices to assess the discriminative ability of prediction models. Baseline models showed good discrimination with c-indices of 0.69, 0.70, and 0.76 for blood pressure control, cholesterol control, and smoking cessation, respectively. Extended models for blood pressure, cholesterol, and smoking yielded improved c-indices of 0.72, 0.71, and 0.78, respectively., Conclusion: Our results indicate that the probability of risk factor control in CHD patients can be accurately assessed using individual and large-area residential characteristics, allowing for an identification of patients who are less likely to achieve risk factor targets., Competing Interests: Conflict of interest: K.K. had research grant support from the European Society of Cardiology (paid to the Imperial College London). K.S.M. had a doctoral fellowship from the German Heart Foundation. All other authors declare that there is no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: The onset of the COVID-19 pandemic saw the suspension of centre-based cardiac rehabilitation (CBCR) and has underscored the need for home-based cardiac telerehabilitation (HBCTR) as a feasible alternative rehabilitation delivery model. Yet, the effectiveness of HBCTR as an alternative to Phase 2 CBCR is unknown. We aimed to conduct a meta-analysis to quantitatively appraise the effectiveness of HBCTR., Methods and Results: PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and PsycINFO were searched from inception to January 2021. We included randomized controlled trials (RCTs) comparing HBCTR to Phase 2 CBCR or usual care in patients with coronary heart disease (CHD). Out of 1588 studies, 14 RCTs involving 2869 CHD patients were included in this review. When compared with usual care, participation in HBCTR showed significant improvement in functional capacity {6-min walking test distance [mean difference (MD) 25.58 m, 95% confidence interval (CI) 14.74-36.42]}; daily step count (MD 1.05 K, 95% CI 0.36-1.75) and exercise habits [odds ratio (OR) 2.28, 95% CI 1.30-4.00)]; depression scores (standardized MD -0.16, 95% CI -0.32 to 0.01) and quality of life [Short-Form mental component summary (MD 2.63, 95% CI 0.06-5.20) and physical component summary (MD 1.99, 95% CI 0.83-3.16)]. Effects on medication adherence were synthesized narratively. HBCTR and CBCR were comparably effective., Conclusion: In patients with CHD, HBCTR was associated with an increase in functional capacity, physical activity (PA) behaviour, and depression when compared with UC. When HBCTR was compared to CBCR, an equivalent effect on functional capacity, PA behaviour, QoL, medication adherence, smoking behaviour, physiological risk factors, depression, and cardiac-related hospitalization was observed., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Despite the high use of cardioprotective medications, the risk factor control in patients with coronary heart disease (CHD) is still inadequate. Guidelines identify healthy lifestyles as equally important in secondary prevention as pharmacotherapy. Here, we describe reasons for poor lifestyle adherence from the patient's perspective., Methods and Results: In the EUROASPIRE IV and V surveys, 16 259 CHD patients were examined and interviewed during a study visit ≥6 months after hospital discharge. Data gathering was fully standardized. The Brief Illness Perception questionnaire was completed by a subsample of 2379 patients. Half of those who were smoking prior to hospital admission, were still smoking; 37% of current smokers had not attempted to quit and 51% was not considering to do so. The prevalence of obesity was 38%. Half of obese patients tried to lose weight in the past month and 61% considered weight loss in the following month. In relation to physical activity, 40% was on target with half of patients trying to do more everyday activities. Less than half had the intention to engage in planned exercise. Only 29% of all patients was at goal for all three lifestyle factors. The number of adverse lifestyles was strongly related to the way patients perceive their illness as threatening. Lifestyle modifications were more successful in those having participated in a cardiac rehabilitation and prevention programme. Patients indicated lack of self-confidence as the main barrier to change their unhealthy behaviour., Conclusion: Modern secondary prevention programmes should target behavioural change in all patients with adverse lifestyles., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Most patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years., Methods and Results: Prospective data were available for 12 484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and the incidence of the primary endpoint was investigated. This model was then validated in the remaining 4484 patients. The final multivariate model revealed a higher risk for the primary endpoint with increasing age, a previous hospitalization for stroke, heart failure or PCI, a previous diagnosis of peripheral artery disease, self-reported diabetes and its glycaemic control, higher non-high-density lipoprotein cholesterol, reduced renal function, symptoms of depression and anxiety and living in a higher risk country. The model demonstrated excellent internal validity and proved very adequate in the validation cohort. Regarding external validity, the model demonstrated good discriminative ability in 20 148 MI patients participating in the SWEDEHEART register. Finally, we developed a risk calculator to estimate risks at 1 and 2 years for patients with stable CHD., Conclusion: In patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: To investigate the population attributable fraction due to elevated lipoprotein (a) (Lp(a)) and the utility of measuring Lp(a) in cardiovascular disease (CVD) risk prediction., Methods and Results: In 413 734 participants from UK Biobank, associations of serum Lp(a) with composite fatal/non-fatal CVD (n = 10 066 events), fatal CVD (n = 3247), coronary heart disease (CHD; n = 18 292), peripheral vascular disease (PVD; n = 2716), and aortic stenosis (n = 901) were compared using Cox models. Median Lp(a) was 19.7 nmol/L (interquartile interval 7.6-75.3 nmol/L). About 20.8% had Lp(a) values >100 nmol/L; 9.2% had values >175 nmol/L. After adjustment for classical risk factors, 1 SD increment in log Lp(a) was associated with a hazard ratio for fatal/non-fatal CVD of 1.12 [95% confidence interval (CI) 1.10-1.15]. Similar associations were observed with fatal CVD, CHD, PVD, and aortic stenosis. Adding Lp(a) to a prediction model containing traditional CVD risk factors in a primary prevention group improved the C-index by +0.0017 (95% CI 0.0008-0.0026). In the whole cohort, Lp(a) above 100 nmol/L was associated with a population attributable fraction (PAF) of 5.8% (95% CI 4.9-6.7%), and for Lp(a) above 175 nmol/L the PAF was 3.0% (2.4-3.6%). Assuming causality and an achieved Lp(a) reduction of 80%, an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above 175 nmol/L may reduce CVD risk by 20.0% and CHD by 24.4%. Similar benefits were also modelled in the whole cohort, regardless of baseline CVD., Conclusion: Population screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs, if such drugs prove efficacious, to those with markedly elevated levels., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Blockade of β-adrenoceptors reduces sympathetic nervous system activity and improves survival in patients with heart failure with reduced left ventricular ejection fraction (HFrEF); however, any improvement in longevity among patients with coronary heart disease (CHD) but without HFrEF remains uncertain. Vitamin A has been linked to the activation of tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine synthesis pathway. We investigated if vitamin A status modified the association of β-blocker use with the risk of all-cause mortality., Methods and Results: A total of 4118 patients undergoing elective coronary angiography for suspected stable angina pectoris, of whom the majority had normal left ventricular ejection fraction (LVEF) were studied. Hazard ratios (HRs) of all-cause mortality comparing treatment vs. non-treatment of β-blockers according to the tertiles of serum vitamin A were explored in Cox proportional hazards regression models. During a median follow-up of 10.3 years, 897 patients (21.8%) died. The overall LVEF was 65% and 283 (6.9%) had anamnestic HF. After multivariable adjustments for traditional risk factors, medical history, and drug therapies of cardiovascular disease, β-blocker treatment was inversely associated with the risk of all-cause mortality [HR : 0.84; 95% CI (confidence interval), 0.72-0.97]. However, the inverse association was generally stronger among patients in the upper serum vitamin A tertile (HR :0.66; 95% CI, 0.50-0.86; Pinteraction = 0.012), which remained present after excluding patients with LVEF < 40%., Conclusion: In patients with suspected CHD, β-blocker treatment was associated with improved survival primarily among patients with high serum vitamin A levels., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites., Methods and Results: A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: -0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman's rho ≤0.40, for all variables)., Conclusion: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Cumulative blood pressure (BP) is a measure that incorporates the severity and duration of BP exposure. The prognostic significance of cumulative BP in young adults for cardiovascular diseases (CVDs) in comparison to BP severity alone is, however, unclear., Methods and Results: We investigated 3667 Coronary Artery Risk Development in Young Adults participants who attended six visits over 15 years (year-0 (1985-1986), year-2, year-5, year-7, year-l0, and year-15 exams). Cumulative BP was calculated as the area under the curve (mmHg × years) from year 0 through year 15. Cox models assessed the association between cumulative BP (year 0 through year 15), current BP (year 15), and BP change (year 0 and year 15) and CVD outcomes. Mean (standard deviation) age at year 15 was 40.2 (3.6) years, 44.1% were men, and 44.1% were African-American. Over a median follow-up of 16 years, there were 47 heart failure (HF), 103 coronary heart disease (CHD), 71 stroke, and 191 CVD events. Cumulative systolic BP (SBP) was associated with HF (hazard ratio (HR) = 2.14 (1.58-2.90)), CHD (HR = 1.49 (1.19-1.87)), stroke (HR = 1.81 (1.38-2.37)), and CVD (HR = 1.73 (1.47-2.05)). For CVD, the C-statistic for SBP (year 15) was 0.69 (0.65-0.73) and change in C-statistic with the inclusion of SBP change and cumulative SBP was 0.60 (0.56-0.65) and 0.72 (0.69-0.76), respectively. For CVD, using year-15 SBP as a reference, the net reclassification index (NRI) for cumulative SBP was 0.40 (p < 0.0001) and the NRI for SBP change was 0.22 (p = 0.001)., Conclusions: Cumulative BP in young adults was associated with the subsequent risk of HF, CHD, stroke, and CVD. Cumulative BP provided incremental prognostic value and improved risk reclassification for CVD, when compared to single BP assessments or changes in BP., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: To determine the impact of preventing new (incident) cases of coronary heart disease (CHD) on years of life and productivity, using the novel measure 'productivity-adjusted life year' (PALY), over the next 10 years., Methods and Results: A dynamic life table model was constructed for the total Australian working-age population (15-69 years) over 10 years (2020-2029), separated by CHD status. Productivity estimates were sourced from the literature. The PALY was ascribed a financial value in terms of gross domestic product (GDP) per equivalent full-time worker. The total number of years lived, PALYs, and economic burden (in terms of GDP per PALY) were estimated. The model simulation was repeated assuming incidence was reduced, and the differences represented the impact of CHD prevention. All outcomes were discounted by 5% per annum. Over 10 years, the total projected years lived and PALYs in the Australian working-age population (with and without CHD) were 133 million and 83 million, respectively, amounting to A$17.2 trillion in GDP. We predicted more than 290 000 new (incident) CHD cases over the next 10 years. If all new cases of CHD could be prevented during this period, a total of 4 000 deaths could be averted, resulting in more than 8 000 years of life saved and 104 000 PALYs gained, equivalent to a gain of nearly A$21.8 billion (US$14.8 billion) in GDP., Conclusion: Prevention of CHD will prolong years of life lived and productive life years, resulting in substantial economic benefit. Policy makers and employers are encouraged to engage in preventive measures addressing CHD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: This population-based cross-stional and panel study investigated disparities in the management of coronary heart disease (CHD) by level of socioeconomic status., Methods: CHD patients (aged ≥18 years), treated in 438 general practices in Australia, with ≥3 recent encounters with their general practitioners, with last encounter being during 2016-2018, were included. Secondary prevention prescriptions and number of treatment targets achieved were each modelled using a Poisson regression adjusting for demographics, socioeconomic indicators, remoteness of patient's residence, comorbidities, lifetime follow-up, number of patient-general practitioner encounters and cluster effect within the general practices. The latter model was constructed using the Generalised Estimating Equations approach. Sensitivity analysis was run by comorbidity., Results: Of 137,408 patients (47% women), approximately 48% were prescribed ≥3 secondary prevention medications. However, only 44% were screened for CHD-associated risk factors. Of the latter, 45% achieved ≥5 treatment targets. Compared with patients from the highest socioeconomic status fifth, those from the lowest socioeconomic status fifth were 8% more likely to be prescribed more medications for secondary prevention (incidence rate ratio (95% confidence interval): 1.08 (1.04-1.12)) but 4% less likely to achieve treatment targets (incidence rate ratio: 0.96 (0.95-0.98)). These disparities were also observed when stratified by comorbidities., Conclusion: Despite being more likely to be prescribed medications for secondary prevention, those who are most socioeconomically disadvantaged are less likely to achieve treatment targets. It remains to be determined whether barriers such as low adherence to treatment, failure to fill prescriptions, low income, low level of education or other barriers may explain these findings., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Improvement in exercise capacity is a main goal of cardiac rehabilitation but the effects are often lost at long-term follow-up and thus also the benefits on prognosis. We assessed whether improvement in VO 2peak during a cardiac rehabilitation programme predicts long-term prognosis., Methods and Results: We performed a retrospective analysis of 1561 cardiac patients completing cardiac rehabilitation in 2011-2017 in Copenhagen. Mean age was 63.6 (11) years, 74% were male and 84% had coronary artery disease, 6% chronic heart failure and 10% heart valve replacement. The association between baseline VO 2peak and improvement after cardiac rehabilitation and being readmitted for cardiovascular disease and/or all-cause mortality was assessed with three different analyses: Cox regression for the combined outcome, for all-cause mortality and a multi-state model. During a median follow-up of 2.3 years, 167 readmissions for cardiovascular disease and 77 deaths occurred. In adjusted Cox regression there was a non-linear decreasing risk of the combined outcome with higher baseline VO 2peak and with improvement of VO 2peak after cardiac rehabilitation. A similar linear association was seen for all-cause mortality. Applying the multi-state model, baseline VO 2peak and change in VO 2peak were associated with risk of a cardiovascular disease readmission and with all-cause mortality but not with mortality in those having an intermediate readmission for cardiovascular disease., Conclusion: VO 2peak as well as change in VO 2peak were highly predictive of future risk of readmissions for cardiovascular disease and all-cause mortality. The predictive value did not extend beyond the next admission for a cardiovascular event.

Background: In the United Kingdom (UK), exercise intensity is prescribed from a fixed percentage range (% heart rate reserve (%HRR)) in cardiac rehabilitation programmes. We aimed to determine the accuracy of this approach by comparing it with an objective, threshold-based approach incorporating the accurate determination of ventilatory anaerobic threshold (VAT). We also aimed to investigate the role of baseline cardiorespiratory fitness status and exercise testing mode dependency (cycle vs . treadmill ergometer) on these relationships., Design and Methods: A maximal cardiopulmonary exercise test was conducted on a cycle ergometer or a treadmill before and following usual-care circuit training from two separate cardiac rehabilitation programmes from a single region in the UK. The heart rate corresponding to VAT was compared with current heart rate-based exercise prescription guidelines., Results: We included 112 referred patients (61 years (59-63); body mass index 29 kg·m -2 (29-30); 88% male). There was a significant but relatively weak correlation ( r  = 0.32; p  = 0.001) between measured and predicted %HRR, and values were significantly different from each other ( p  = 0.005). Within this cohort, we found that 55% of patients had their VAT identified outside of the 40-70% predicted HRR exercise training zone. In the majority of participants (45%), the VAT occurred at an exercise intensity <40% HRR. Moreover, 57% of patients with low levels of cardiorespiratory fitness achieved VAT at <40% HRR, whereas 30% of patients with higher fitness achieved their VAT at >70% HRR. VAT was significantly higher on the treadmill than the cycle ergometer ( p <  0.001)., Conclusion: In the UK, current guidelines for prescribing exercise intensity are based on a fixed percentage range. Our findings indicate that this approach may be inaccurate in a large proportion of patients undertaking cardiac rehabilitation.

Background: We tested the hypothesis that a single high sensitivity troponin at limits of detection (LOD HSTnT) (<5 ng/l) combined with a presentation non-ischaemic electrocardiogram is superior to low-risk Global Registry of Acute Coronary Events (GRACE) (<75), Thrombolysis in Myocardial Infarction (TIMI) (≤1) and History, ECG, Age, Risk factors and Troponin (HEART) score (≤3) as an aid to early, safe discharge for suspected acute coronary syndrome., Methods: In a prospective cohort study, risk scores were computed in consecutive patients with suspected acute coronary syndrome presenting to the Emergency Room of a large English hospital. Adjudication of myocardial infarction, as per third universal definition, involved a two-physician, blinded, independent review of all biomarker positive chest pain re-presentations to any national hospital. The primary and secondary outcome was a composite of type 1 myocardial infarction, unplanned coronary revascularisation and all cause death (MACE) at six weeks and one year., Results: Of 3054 consecutive presentations with chest pain 1642 had suspected acute coronary syndrome (52% male, median age 59 years, 14% diabetic, 20% previous myocardial infarction). Median time from chest pain to presentation was 9.7 h. Re-presentations occurred in eight hospitals with 100% follow-up achieved. Two hundred and eleven (12.9%) and 279 (17%) were adjudicated to suffer MACE at six weeks and one year respectively. Only HEART ≤3 (negative predictive value MACE 99.4%, sensitivity 97.6%, %discharge 53.4) and LOD HSTnT strategy (negative predictive value MACE 99.8%, sensitivity 99.5%, %discharge 36.9) achieved pre-specified negative predictive value of >99% for MACE at six weeks. For type 1 myocardial infarction alone the negative predictive values at six weeks and one year were identical, for both HEART ≤3 and LOD HSTnT at 99.8% and 99.5% respectively., Conclusion: HEART ≤3 or LOD HSTnT strategy rules out short and medium term myocardial infarction with ≥99.5% certainty, and short-term MACE with >99% certainty, allowing for early discharge of 53.4% and 36.9% respectively of suspected acute coronary syndrome. Adoption of either strategy has the potential to greatly reduce Emergency Room pressures and minimise follow-up investigations. Very early presenters (<3 h), due to limited numbers, are excluded from these conclusions.

Objective: To analyze the performance characteristics, stability, and clinical value of lipoprotein-associated phospholipase A2 (Lp-PLA2) using an enzymatic kinetic method., Methods: The performance characteristics included reference intervals, precision, and accuracy. We assessed Lp-PLA2 stability by comparing Lp-PLA2 changes under different conditions. Lp-PLA2 was determined in the following groups: control individuals, patients with coronary heart disease (CHD), patients of different lipid subgroups within CHD, and patients with high total cholesterol (TC). Also, correlations between Lp-PLA2 and traditional cardiovascular risk factors were assessed., Results: The mean (SD) reference interval of serum Lp-PLA2 activity was 451 (113) U per L with sex differences. Inter- and intra-assay precision revealed coefficients of variance (CVs) of 1.81% to 2.63% and 1.43% to 1.77%. The average bias was 0.33%. Lp-PLA2 activity was stable. In the CHD group, high-lipid subgroups, and high-TC group, Lp-PLA2 was elevated, and correlation was observed between Lp-PLA2 and traditional risk factors., Conclusion: Lp-PLA2 activity has important clinical value in CHD., (© American Society for Clinical Pathology 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate the sex-specific associations of prediabetes with major clinical outcomes including incident type 2 diabetes, chronic kidney disease, hypertension, coronary heart disease, stroke and all-cause mortality., Methods: Among 8498 Iranian adults from the Tehran Lipid and Glucose Study, aged ≥30 years and without diagnosed type 2 diabetes, gender-interactions were assessed for each outcome, followed by sex-separated multivariate-adjusted Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals (CIs) of different prediabetes categories, including impaired fasting glucose (IFG), defined by the American Diabetes Association (ADA) and World Health Organization (WHO), as fasting plasma glucose of 5.6-6.9 mmol/L and 6.1-6.9 mmol/L, respectively, and impaired glucose tolerance, defined as 2-h post challenge plasma glucose of 7.8-11 mmol/L., Results: Sex-specific associations existed for men between IFG-ADA and chronic kidney disease (hazard ratio: 1.28, 95% CI 0.99-1.65; p interaction  = 0.008) and between IFG-WHO and stroke (hazard ratio: 2.15, 95% CI 1.08-4.27; p interaction  = 0.21); and for women between IFG-ADA and hypertension (hazard ratio: 1.24, 95% CI 1.04-1.48; p interaction  = 0.06) and between impaired glucose tolerance and coronary heart disease (hazard ratio: 1.57, 95% CI 1.14-2.16; p interaction  = 0.05). Among both genders, all prediabetes definitions were associated with type 2 diabetes but none with mortality., Conclusions: The hazards of prediabetes definitions may differ between genders depending on the outcome of interest. IFG-WHO among men and impaired glucose tolerance among women are particularly important because of their association with incident stroke and coronary heart disease, respectively. Considering these sex differences could improve personalized management of prediabetes.

Background: Coronary heart disease (CHD) is among the main causes of death in the world. Individual study of cardiovascular risk is an important way to predict CHD risk. The aim of this study was to evaluate the added role of the aortic pulse wave velocity (PWV) index in the prediction of CHD risk., Methods: A cross-sectional study was conducted from December 2012 to September 2017; 530 patients were included: 99 CHD, 338 non-CHD patients, and 93 nonhypertensives, nondiabetics and non-CHD subjects, whose theoretical PWV were calculated. Theoretical PWV was calculated according to age, blood pressure, gender, and heart rate. The results were expressed as an index ((measured PWV - theoretical PWV)/theoretical PWV) for each patient. The differences observed, the differential diagnostic performance, and the quantification of the added value of diagnostic performance of PWV index were tested using logistic regression, comparisons between receiver operating characteristic (ROC) curves, and decision tree nonlinear methodology., Results: PWV index (P = 0.006), carotid plaque (P = 0.005), and dyslipidemia (P = 0.04) were the independent modulators of CHD diagnosis. PWV index appears to be the highest specific classifier (81%) compared to carotid plaque (75%) and dyslipidemia (78%). For the decision tree, sensitivity, specificity, and area under the ROC curve for CHD diagnosis were 62%, 83%, and 0.87, respectively., Conclusions: PWV index yielded added value to CHD by assessment of combined classifiers with clinical determinants and decision tree construction and significantly increased the specificity of the differential diagnostic performances of the common risk factors of CHD in daily clinical practice., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background Mortality from cardiovascular diseases is particularly high in Russia compared with the European average. The National Priority Project 'Health', launched in 2005, aimed to promote prevention of non-communicable diseases, particularly cardiovascular diseases, in primary care and to increase availability of state-of-art cardiovascular disease management. Methods This is a multiregional population based study with analysis of indicators for cardiovascular health and coronary heart disease in Moscow, St Petersburg, the Moscow region and across Russia, including a total population of 143.7 million inhabitants between 2005 and 2013. Data were collected using conventional methodology and originate from open statistical sources. Results The overall age-standardized coronary heart disease mortality decreased in 2005-2013 by 24.7% from 383.6 to 289.0 per 100000 population, but with substantial interregional differences: it declined from 306.1 to 196.9 per 100,000 in Moscow (-35.7%), from 362.1 to 258.9 per 100,000 in St Petersburg (-28.5%) and from 433.8 to 374.3 per 100,000 in the Moscow region (-13.7%). Income in Moscow exceeded the national average 2-3-fold, and Moscow had the highest availability of modern treatments and interventions. Although vegetables, fruits and fish consumption increased overall in Russia, this trend was most prominent in Moscow. Indicators for psychosocial well-being also were best in Moscow. Life expectancy in Moscow is almost six years higher than the Russian average. Conclusion Health policy interventions turned out to be successful but with substantial interregional differences. Lower coronary heart disease mortality and higher life expectancy in Moscow may be due to a more favourable socioeconomic and psychological environment, more healthy eating and greater availability of medical care.

Objectives: Our goal was to evaluate the expressions of 14 selected pro-angiogenic micro-ribonucleic acids in patients with coronary heart disease (CHD) and healthy controls (HCs) and to assess the correlations of those micro-ribonucleic acids with risk and severity of CHD., Methods: In the exploration stage, 20 patients with CHD were enrolled; in the validation stage, 102 patients with CHD and 92 age- and gender-matched HCs with the same eligibility of those in the exploration stage were recruited. Blood samples were collected from all participants, and plasma levels of micro-ribonucleic acids were measured by the quantitative polymerase chain reaction method., Results: In the exploration stage, the expression of miR-126, miR-17-5p, miR-19a, miR-92a, miR-210 and miR-378 in patients with CHD was down-regulated compared with that of HCs. In the validation stage, miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 levels decreased remarkably in patients with CHD compared with the HCs. Plasma levels of miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 were independent prediction factors for CHD. The combination of miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 was of good diagnostic value for CHD with an area under the curve of 0.756. Additionally, plasma levels of miR-126, miR-210 and miR-378 correlated negatively with Gensini scores., Conclusions: Circulating miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 could serve as novel, promising biomarkers for risk and severity of CHD. Additionally, miR-126, miR-210 and miR-378 were negatively associated with Gensini scores.

Background Anxiety and depression are related to coronary heart disease, and psychological support is recommended in cardiac rehabilitation. Purpose The aims of this study were: to compare the prevalence of anxiety and depression with respect to cardiac rehabilitation participation among patients who have been treated with percutaneous coronary intervention; to examine prevalence of anxiety and depression among percutaneous coronary intervention patients compared to the general population; and to identify predictors of symptomatic anxiety and depression among percutaneous coronary intervention patients. Methods We included 9013 patients undergoing first-time percutaneous coronary intervention. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale in a representative sample of 775 patients at baseline and after three years of follow-up, and in the entire cohort at three-year follow-up. Results Cardiac rehabilitation participants had more anxiety and depression than cardiac rehabilitation non-participants at baseline, and both groups had a more anxiety than the general population. The levels of anxiety and depression fell significantly during three years of follow-up, but the changes did not differ between cardiac rehabilitation participants and cardiac rehabilitation non-participants. Three years after percutaneous coronary intervention the prevalence of anxiety was 32% ( p < 0.001), higher among cardiac rehabilitation participants compared to cardiac rehabilitation non-participants. Female gender and younger age were associated with anxiety, whereas older age, lower levels of education and cardiovascular morbidity were associated with depression. Conclusion The levels of anxiety and depression were prevalent among percutaneous coronary intervention patients and the levels were not affected by cardiac rehabilitation participation. Anxiety is prevalent among female and younger patients, whereas depression is related to older age and cardiovascular co-morbidity.

Background: Socioeconomic inequalities in coronary heart disease (CHD)-related morbidity and mortality are well explored. However, less is known about the causes of inequalities in CHD treatment. In this qualitative study, we explored socioeconomic differences in the pathways to diagnosis of CHD., Methods: The data originated from 38 semi-structured interviews with older CHD patients, aged 59-80 years, conducted at the university hospital in Halle, Germany, between November 2014 and April 2015. We analysed the narratives related to the time before CHD was confirmed by coronary angiography electively or urgently. Transcripts were analysed following inductive qualitative content analysis and we identified socioeconomic differences by comparing and contrasting patients' narratives., Results: The patients interpreted their symptoms based on expectations, normalization, relief and obtaining help from third parties. For those experiencing chronic CHD symptoms, only patients with low socioeconomic status (SES) waited to seek healthcare until they suffered myocardial infarction. Mainly low-SES patients procrastinated in undergoing diagnostic procedures. We found no socioeconomic differences in the urgent pathway. However, along the elective pathway, only low-SES patients reported receiving assistance from a general practitioner in accessing a cardiologist., Conclusions: Socioeconomic differences in CHD diagnosis were mainly apparent before patients sought healthcare. These differences were more pronounced when CHD was electively diagnosed due to chronic symptoms rather than urgently diagnosed due to acute symptoms. To address socioeconomic differences, general practitioners should focus on any indication of symptoms and interpretation mentioned by low-SES patients, and coordinate these patients' pathways to diagnosis while emphasizing the seriousness of CHD., (© The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: A number of lipoprotein(a) [Lp(a)] analytical techniques are available that quantify distinct particle components, yet their clinical efficacy has not been comprehensively evaluated. This study determined whether Lp(a) mass [Lp(a)-M], Lp(a) cholesterol content [Lp(a)-C], and particle concentration [Lp(a)-P] differentially discriminated risk of calcific aortic valve disease (CAVD) or incident coronary heart disease (CHD) among 4679 participants of the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: Lp(a)-M, Lp(a)-C, and Lp(a)-P were measured in individuals without clinical evidence of CHD at baseline. Relative risk regression and Cox proportional analysis determined associations between Lp(a) and the presence of CAVD or 12-year risk of CHD, respectively. To control for the relatively high lower limits of quantification for Lp(a)-C and Lp(a)-P assays, the upper 25th and 15th percentiles were selected as analytical cutoff points., Results: Regardless of method or analytical cutoff, high Lp(a) concentrations were significantly associated with CAVD and CHD in MESA participants following adjustment for typical cardiovascular risk factors. Stratifying by race/ethnicity rendered most associations nonsignificant after correction for multiple comparisons, but Lp(a) remained associated with CAVD in whites irrespective of method (all P < 0.0001)., Conclusions: Associations of Lp(a)-C, Lp(a)-P, and Lp(a)-M with CAVD or incident CHD were similar in this entire MESA sample using a dichotomized statistical approach. However, the high lower limits of quantification and imprecision of the Lp(a)-C and Lp(a)-P assays limited their usefulness in our analyses and would likely do so in research and clinical settings., (© 2017 American Association for Clinical Chemistry.)

Aims The aim of this study was to investigate the impact of persistence and non-persistence in leisure time physical activity on coronary heart disease and all-cause mortality. Methods and results In the Copenhagen City Heart Study, we prospectively followed 12,314 healthy subjects for 33 years of maximum follow-up with at least two repeated measures of physical activity. The association between persistence and non-persistence in leisure time physical activity, coronary heart disease and all-cause mortality were assessed by multivariable Cox regression analyses. Coronary heart disease mortality for persistent physical activity in leisure compared to persistent sedentary activity were: light hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.63-0.92, moderate HR 0.52; 95% CI 0.41-0.67, and high physical activity HR 0.51; 95% CI, 0.30-0.88. The differences in longevity were 2.8 years for light, 4.5 years for moderate and 5.5 years for high physical activity. A substantial increase in physical activity was associated with lower coronary heart disease mortality (HR 0.75; 95% CI 0.52-1.08) corresponding to 2.4 years longer life, whereas a substantial decrease in physical activity was associated with higher coronary heart disease mortality (HR 1.61; 95% CI 1.11-2.33) corresponding to 4.2 years shorter life than the unchanged group. A similar pattern was observed for all-cause mortality. Conclusion We found inverse dose-response relationships between persistent leisure time physical activity and both coronary heart disease and all-cause mortality. A substantial increase in physical activity was associated with a significant gain in longevity, whereas a decrease in physical activity was associated with even greater loss of longevity.

Background The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) was a randomized controlled trial of a group-based cognitive behavioural therapy stress management programme for patients with coronary heart disease. The project was successful in reducing the risk of fatal or non-fatal first recurrent cardiovascular events. The aim of this study was to analyse the effect of cognitive behavioural therapy on self-rated stress, somatic anxiety, vital exhaustion and depression and to study the associations of these factors with the reduction in cardiovascular events. Methods A total of 362 patients were randomly assigned to intervention or usual care groups. The psychological outcomes were assessed five times during 24 months and analysed using linear mixed models. The mediating roles of the outcomes were analysed using joint modelling of the longitudinal and time to event data. Results The intervention had a positive effect on somatic anxiety ( p < 0.05), reflecting a beneficial development over time compared with the controls. Stress, vital exhaustion and depression did not differ between the groups over time. Mediator analysis suggested that somatic anxiety may have mediated the effect of treatment on cardiovascular events. Conclusions The intervention had a small positive effect on somatic anxiety, but did not affect stress, vital exhaustion or depression in patients with coronary heart disease. Somatic anxiety was associated with an increased risk of cardiovascular events and might act as a partial mediator in the treatment effect on cardiovascular events. However, the mechanisms between the intervention and the protective cardiovascular outcome remain to be identified.

Background Low testosterone levels have been associated with coronary heart disease (CHD) morbidity and mortality in men, but the influence of hormones in postmenopausal women is unclear. This meta-analysis aimed to examine whether there is an association between endogenous sex hormones and CHD risk in postmenopausal women. Methods A systematic search of the PubMed and EMBASE databases from 1966 to 30 November 2016 was performed for prospective studies that reported an association between endogenous sex hormones and CHD in postmenopausal women. Summary relative risks (RRs) and 95% confidence intervals (CIs) were combined by using a random-effects model. Results A total of 13 publications (12 studies, including six prospective cohort and six nested case-control studies) were included. The summary RRs for CHD were 1.01 (95% CI 0.77-1.31) comparing the highest versus lowest tertile of total testosterone, with evidence of high heterogeneity ( I 2  = 80.7%). In subgroup and meta-regression analyses, none of the variables were identified as contributing to significant heterogeneity. Based on a comparison of the highest versus lowest tertile models, the summary RRs (95% CIs) for CHD were 0.88 (0.63-1.23, I 2  = 48.7%) for free testosterone, 1.16 (0.82-1.63, I 2  = 47.8%) for estradiol, 0.98 (0.90-1.07, I 2  = 3.2%) for sex hormone-binding globulin and 1.19 (0.89-1.58, I 2  = 0) for dehydroepiandrosterone. Conclusion There is limited evidence to suggest that endogenous levels of sex hormones are not significantly associated with CHD risk in postmenopausal women.

Background Metabolic syndrome (MetS) is associated with increased risk for cardiovascular disease, but there is heterogeneity in this risk. We evaluated whether high-sensitivity troponin T (hs-cTnT), a marker associated with cardiovascular disease, can stratify risk in MetS. Methods We evaluated associations between MetS (and groups with similar number of MetS components) and incident heart failure hospitalization, coronary heart disease, stroke and death using hs-cTnT categories after adjusting for risk factors/markers between 1996 and 2011 in 8204 individuals in the Atherosclerosis Risk In Communities study. Results The mean age of the population was 63 years (56% women, 19% Blacks). hs-cTnT levels were higher with MetS and with increasing MetS components. In individuals with MetS, higher hs-cTnT levels were associated with increased hazard ratios for heart failure, coronary heart disease and death. Within each number of MetS components, higher hs-cTnT was associated with progressively higher heart failure, coronary heart disease and death hazards. The association was particularly strong for heart failure. With increasing hs-cTnT categories, the hazard ratios (95% confidence interval) for heart failure in individuals with MetS increased gradually from 1.68 (1.31-2.16) to 3.76 (2.69-5.26) ( p-trend < 0.001) compared with those with MetS and hs-cTnT < 5 ng/l; and respective hazard ratios with increasing hs-cTnT categories in those with all five MetS components ranged from 2.22 (1.17-4.21) to 4.23 (1.89-9.50) ( p-trend 0.004) compared with those with all five MetS components and hs-cTnT < 5 ng/l. However, mostly there were no significant interactions of hs-cTnT with MetS or its components. Conclusion hs-cTnT is useful for identifying MetS patients with increased hazards for coronary heart disease, death and particularly heart failure.

Takayasu arteritis (TA) is a rare idiopathic large-vessel vasculitis involving the aorta and its major branches. Coronary artery disease and its surgical management in patients with TA is also a rare clinical entity. We report the case of a 73-year-old woman with TA and 3-vessel coronary artery disease in whom we performed off-pump coronary artery bypass graft concomitant with supra-aortic vessel revascularization., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA 2 enzyme activity is causally relevant to coronary heart disease. Methods In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.109+2T > C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7, the gene encoding Lp-PLA 2 . We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patients and 88,680 controls in publicly available databases and other previous studies. We conducted a systematic review of randomized trials to compare effects of darapladib treatment on soluble Lp-PLA 2 activity, conventional cardiovascular risk factors, and coronary heart disease risk with corresponding effects of Lp-PLA 2 -lowering alleles. Results Lp-PLA 2 activity was decreased by 64% ( p = 2.4 × 10 -25 ) with carriage of any of the four loss-of-function variants, by 45% ( p < 10 -300 ) for every allele inherited at Val279Phe, and by 2.7% ( p = 1.9 × 10 -12 ) for every allele inherited at Val379Ala. Darapladib 160 mg once-daily reduced Lp-PLA 2 activity by 65% ( p < 10 -300 ). Causal risk ratios for coronary heart disease per 65% lower Lp-PLA 2 activity were: 0.95 (0.88-1.03) with Val279Phe; 0.92 (0.74-1.16) with carriage of any loss-of-function variant; 1.01 (0.68-1.51) with Val379Ala; and 0.95 (0.89-1.02) with darapladib treatment. Conclusions In a large-scale human genetic study, none of a series of Lp-PLA 2 -lowering alleles was related to coronary heart disease risk, suggesting that Lp-PLA 2 is unlikely to be a causal risk factor.

Background: Regular exercise lowers the risk of cardiovascular death in coronary heart disease (CHD) patients. We aimed to investigate regular exercise behaviour and intention in relation to symptoms of anxiety and depression in CHD patients across Europe., Design: This study was based on a multicentre cross-sectional survey., Methods: In the EUROpean Action on Secondary and Primary Prevention through Intervention to Reduce Events (EUROASPIRE) III survey, 8966 CHD patients <80 years of age from 22 European countries were interviewed on average 15 months after hospitalisation. Whether patients exercised or intended to exercise regularly was assessed using the Stages of Change questionnaire in 8330 patients. Symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. Total physical activity was measured by the International Physical Activity Questionnaire in patients from a subset of 14 countries., Results: Overall, 50.3% of patients were not intending to exercise regularly, 15.9% were intending to exercise regularly, and 33.8% were exercising regularly. Patients with severe symptoms of depression less frequently exercised regularly than patients with symptoms in the normal range (20.2%, 95% confidence interval (CI) 14.8-26.8 vs 36.7%, 95% CI 29.8-44.2). Among patients not exercising regularly, patients with severe symptoms of depression were less likely to have an intention to exercise regularly (odds ratio 0.62, 95% CI 0.46-0.85). Symptoms of anxiety did not affect regular exercise intention. In sensitivity analysis, results were consistent when adjusting for total physical activity., Conclusions: Lower frequency of regular exercise and decreased likelihood of exercise intention were observed in CHD patients with severe depressive symptoms. Severe symptoms of depression may preclude CHD patients from performing regular exercise., (© The European Society of Cardiology 2016.)

Background: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited., Methods: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed., Results: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI., Conclusions: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903., (© 2016 American Association for Clinical Chemistry.)

Background Although numerous phenotype based equations for predicting risk of 'hard' coronary heart disease are available, data on the utility of genetic information for such risk prediction is lacking in Chinese populations. Design Case-control study nested within the Singapore Chinese Health Study. Methods A total of 1306 subjects comprising 836 men (267 incident cases and 569 controls) and 470 women (128 incident cases and 342 controls) were included. A Genetic Risk Score comprising 156 single nucleotide polymorphisms that have been robustly associated with coronary heart disease or its risk factors ( p < 5 × 10 -8 ) in at least two independent cohorts of genome-wide association studies was built. For each gender, three base models were used: recalibrated Adult Treatment Panel III (ATPIII) Model (M 1 ); ATP III model fitted using Singapore Chinese Health Study data (M 2 ) and M 3 : M 2 + C-reactive protein + creatinine. Results The Genetic Risk Score was significantly associated with incident 'hard' coronary heart disease ( p for men: 1.70 × 10 -10 -1.73 × 10 -9 ; p for women: 0.001). The inclusion of the Genetic Risk Score in the prediction models improved discrimination in both genders (c-statistics: 0.706-0.722 vs. 0.663-0.695 from base models for men; 0.788-0.790 vs. 0.765-0.773 for women). In addition, the inclusion of the Genetic Risk Score also improved risk classification with a net gain of cases being reclassified to higher risk categories (men: 12.4%-16.5%; women: 10.2% (M 3 )), while not significantly reducing the classification accuracy in controls. Conclusions The Genetic Risk Score is an independent predictor for incident 'hard' coronary heart disease in our ethnic Chinese population. Inclusion of genetic factors into coronary heart disease prediction models could significantly improve risk prediction performance.

Background: Galectin-3 has emerged as a potential useful novel biomarker for heart failure and cardiovascular disease (CVD). However, it remains unclear whether galectin-3 is associated with recurrent cardiovascular events during long-term follow-up of patients with stable coronary heart disease (CHD) after adjustment for multiple established and novel risk factors., Methods: We measured galectin-3 at baseline in a cohort consisting of 1035 CHD patients and followed them for 13 years to assess a combined CVD end point. Moreover, we adjusted for multiple traditional and novel risk factors., Results: Galectin-3 concentration was positively associated with the number of affected coronary arteries, history of heart failure, and multiple traditional risk factors. Also, galectin-3 correlated significantly with emerging risk factors [e.g., cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity (hs)-troponin]. During follow-up (median 12.0 years), 260 fatal and nonfatal CVD events occurred. The top quartile of galectin-3 concentration was significantly associated with CVD events compared to the bottom quartile after adjustment for age and sex [hazard ratio (HR) 1.88 (95% CI, 1.30-2.73), P = 0.001 for trend] as well as for established CVD risk factors (HR 1.67, 95% CI, 1.14-2.46, P = 0.011 for trend). However, after adjustment for other biomarkers available [including eGFR (estimated glomerular filtration rate), sST2 protein, GDF-15 (growth differentiation factor 15), NT-proBNP, and hs-troponin], the association was no longer statistically significant [HR 1.11 (95% CI 0.72-1.70), P = 0.82 for trend]., Conclusions: Galectin-3 does not independently predict recurrent cardiovascular events in patients with established CHD after adjustment for markers of hemodynamic stress, myocardial injury, inflammation, and renal dysfunction., (© 2016 American Association for Clinical Chemistry.)

Background: Participation in social activities is thought to prevent heart disease, but evidence is inconclusive., Design: We assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women., Methods: Women reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities., Results: After adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81-0.86), but changed to 1.06 (99% confidence interval 1.02-1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations., Conclusions: Associations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants., (© The European Society of Cardiology 2015.)

Aims: To determine whether the Joint European Societies guidelines on cardiovascular prevention are being followed in everyday clinical practice of secondary prevention and to describe the lifestyle, risk factor and therapeutic management of coronary patients across Europe., Methods and Results: EUROASPIRE IV was a cross-sectional study undertaken at 78 centres from 24 European countries. Patients <80 years with coronary disease who had coronary artery bypass graft, percutaneous coronary intervention or an acute coronary syndrome were identified from hospital records and interviewed and examined ≥ 6 months later. A total of 16,426 medical records were reviewed and 7998 patients (24.4% females) interviewed. At interview, 16.0% of patients smoked cigarettes, and 48.6% of those smoking at the time of the event were persistent smokers. Little or no physical activity was reported by 59.9%; 37.6% were obese (BMI ≥ 30 kg/m(2)) and 58.2% centrally obese (waist circumference ≥ 102 cm in men or ≥88 cm in women); 42.7% had blood pressure ≥ 140/90 mmHg (≥140/80 in people with diabetes); 80.5% had low-density lipoprotein cholesterol ≥ 1.8 mmol/l and 26.8% reported having diabetes. Cardioprotective medication was: anti-platelets 93.8%; beta-blockers 82.6%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75.1%; and statins 85.7%. Of the patients 50.7% were advised to participate in a cardiac rehabilitation programme and 81.3% of those advised attended at least one-half of the sessions., Conclusion: A large majority of coronary patients do not achieve the guideline standards for secondary prevention with high prevalences of persistent smoking, unhealthy diets, physical inactivity and consequently most patients are overweight or obese with a high prevalence of diabetes. Risk factor control is inadequate despite high reported use of medications and there are large variations in secondary prevention practice between centres. Less than one-half of the coronary patients access cardiac prevention and rehabilitation programmes. All coronary and vascular patients require a modern preventive cardiology programme, appropriately adapted to medical and cultural settings in each country, to achieve healthier lifestyles, better risk factor control and adherence with cardioprotective medications., (© The European Society of Cardiology 2015.)

Background: Coronary heart disease has become a major health concern over the past several decades. Several reviews have assessed the effects of socioeconomic status on the coronary heart disease epidemic in communities and countries, but only a few reviews have been performed at a global level. This study was to explore the relationship between the prevalence of coronary heart disease and socioeconomic development worldwide using the Human Development Index., Design: Systematic review., Methods: The data in this study were collected from the MEDLINE database. Cross-sectional studies reporting the prevalence of coronary heart disease until November 2014 were collected. The Human Development Index was sourced from the United Nations Development Programme Database and was used to measure the socioeconomic achievements of countries. Each country was classified as a developing or developed country based on its level of development according to the Human Development Index value., Results: Based on the data analysis on the global level, coronary heart disease prevalence had no association with the national Human Development Index (rho = 0.07). However, there was a positive association between coronary heart disease prevalence and the national Human Development Index in developing countries, although a negative association existed in developed countries (rho = 0.47 and -0.34, respectively). In addition, the past decades have witnessed a growing coronary heart disease epidemic in developing countries, with reverse trends observed in developed countries (P = 0.021 and 0.002, respectively)., Conclusions: With the development of socioeconomic status, as measured by the Human Development Index, the prevalence of coronary heart disease is growing in developing countries, while declining in developed countries. Future research needs to pay more attention to the reasonable allocation of medical resources and control of coronary heart disease risk factors., (© The European Society of Cardiology 2015.)

Background: Cystatin C, a marker for early stage chronic kidney dysfunction, mediates the pathogenesis of cardiovascular diseases., Objective: To investigate whether serum cystatin C is an independent predictor of coronary heart disease (CHD) for patients without chronic kidney disease (CKD)., Methods: In this cross-sectional study, we included 525 patients with CHD and 142 apparently healthy control individuals and acquired their demographic characteristics, medical histories, and listings of the concurrent medications they were taking. All patients with CHD underwent coronary angiography and other routine laboratory examinations. We quantified serum concentrations of cystatin C via particle-enhanced immunonephelometric assay., Results: Compared with controls, the patients with CHD had higher serum cystatin C levels (median: 1.17 mg/L, interquartile range [IQR]: 1.01 to 1.46 mg/L vs median: 0.98 mg/L, IQR: 0.80 to 1.06 mg/L, P <.001), lower levels of high-density lipoprotein cholesterol (P <.001), higher levels of low-density lipoprotein cholesterol (P <.001), triglyceride (P <.001), total cholesterol (P = .007) and high-sensitivity C-reactive protein (P <.001). No differences occurred in serum concentrations of creatinine or estimated glomerular filtration rate between CHD patients and healthy controls. Multivariate logistic regression indicated that levels of cystatin C (OR, 1.648; 95% confidence interval [CI], 1.454 to 1.868; P <.001) were most strongly correlated with CHD prevalence., Conclusions: Elevated serum cystatin C is a potential biochemical marker for the prediction of CHD, which suggests that mild preclinical renal dysfunction may be associated with the pathogenesis of CHD., (© American Society for Clinical Pathology, 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)