Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Roles of allostatic load, lifestyle and clinical risk factors in mediating the association between education and coronary heart disease risk in Europe.

BACKGROUND: Previous studies have shown that differential exposure to lifestyle factors may mediate the association between education and coronary heart diseases (CHD). However, few studies have examined the potential roles of allostatic load (AL) or differential susceptibility. METHODS: 25 310 men and 26 018 women aged 35-74 and CHD free at baseline were identified from 21 European cohorts and followed for a median of 10 years, to investigate the mediating role of AL, as well as of smoking, alcohol use and body mass index (BMI), on educational differences in CHD incidence, applying marginal structural models and three-way decomposition. RESULTS: AL is a mediator of the association between educational status and CHD incidence, with the highest proportion mediated observed among women and largely attributable to differential exposure, (28% (95% CI 19% to 44%)), with 8% (95% CI 0% to 16%) attributable to differential susceptibility. The mediating effects of smoking, alcohol and BMI, compared with AL, were relatively small for both men and women. CONCLUSION: Overall, the educational inequalities in CHD incidence were partially mediated through differential exposure to AL. By contrast, the mediation of the educational gradient in CHD by investigated lifestyle risk factors was limited. As differential susceptibility in men was found to have a predominant role in the accumulation of AL in low educational classes, the investigation of AL-related risk factors is warranted.

Pre-graduation medical training including virtual reality during COVID-19 pandemic: a report on students' perception.

BACKGROUND: The Coronavirus Disease 19 (COVID-19) pandemic brought significant disruption to in-hospital medical training. Virtual reality simulating the clinical environment has the potential to overcome this issue and can be particularly useful to supplement the traditional in-hospital medical training during the COVID-19 pandemic, when hospital access is banned for medical students. The aim of this study was to assess medical students' perception on fully online training including simulated clinical scenarios during COVID-19 pandemic. METHODS: From May to July 2020 when in-hospital training was not possible, 122 students attending the sixth year of the course of Medicine and Surgery underwent online training sessions including an online platform with simulated clinical scenarios (Body Interact™) of 21 patient-based cases. Each session focused on one case, lasted 2 h and was divided into three different parts: introduction, virtual patient-based training, and debriefing. In the same period, adjunctive online training with formal presentation and discussion of clinical cases was also given. At the completion of training, a survey was performed, and students filled in a 12-item anonymous questionnaire on a voluntary basis to rate the training quality. Results were reported as percentages or with numeric ratings from 1 to 4. Due to the study design, no sample size was calculated. RESULTS: One hundred and fifteen students (94%) completed the questionnaire: 104 (90%) gave positive evaluation to virtual reality training and 107 (93%) appreciated the format in which online training was structured. The majority of participants considered the platform of virtual reality training realistic for the initial clinical assessment (77%), diagnostic activity (94%), and treatment options (81%). Furthermore, 97 (84%) considered the future use of this virtual reality training useful in addition to the apprenticeship at patient's bedside. Finally, 32 (28%) participants found the online access difficult due to technical issues. CONCLUSIONS: During the COVID-19 pandemic, online medical training including simulated clinical scenarios avoided training interruption and the majority of participant students gave a positive response on the perceived quality of this training modality. During this time frame, a non-negligible proportion of students experienced difficulties in online access to this virtual reality platform.

Decomposing the educational gradient in allostatic load across European populations. What matters the most: differentials in exposure or in susceptibility?

BACKGROUND: We investigate whether socially disadvantaged individuals are more susceptible to the detrimental effects of smoking and alcohol intake on allostatic load (AL), a marker of physiological 'wear and tear', resulting from adaptation to chronic stress. METHODS: In a cross-sectional analysis, 27 019 men and 26 738 women aged 35-74 years were identified from 21 European cohorts in the BiomarCaRE consortium. We defined three educational classes (EDs) according to years of schooling and an AL score as the sum of z-scores of eight selected biomarkers from the cardiovascular, metabolic and inflammatory systems. We used the Oaxaca-Blinder decomposition to disentangle the ED gradient in AL score into the differential exposure (DE, attributable to different distribution of smoking and alcohol intake across EDs) and the differential susceptibility (DS, attributable to a different effect of risk factors on AL across EDs) components. RESULTS: Less-educated men (mean AL difference: 0.68, 95% CI 0.57 to 0.79) and women (1.52, 95% CI 1.40 to 1.64) had higher AL scores. DE accounted for 7% and 6% of the gradient in men and women, respectively. In men, combining smoking and alcohol intake, DS accounted for 42% of the gradient (smoking DS coefficient=0.177, 26% of the gradient; alcohol DS coefficient=0.109; 16%, not statistically significant). DS contribution increased to 69% in metabolic markers. DS estimates were consistent across age groups, irrespective of comorbidities and robust to unmeasured confounding. No DS was observed in women. CONCLUSIONS: In men, a DS mechanism substantially contributes to the educational class gradient in allostatic load.

Prevalence of Abdominal Aortic Aneurysms in the General Population and in Subgroups at High Cardiovascular Risk in Italy. Results of the RoCAV Population Based Study.

OBJECTIVES: Prevalence data on abdominal aortic aneurysm (AAA) in women, subjects younger than 65 years and in subgroups carrying specific risk factors are scarce. AAA prevalence was evaluated in an Italian population including women and younger subjects, stratifying for the presence of cardiovascular disease (CVD) risk factors and CVD risk score. MATERIALS AND METHODS: A population based cross-sectional study was conducted between 2013 and 2016. Men aged 50-75 and women aged 60-75 years, resident in the city of Varese (northern Italy), were randomly selected from the civil registry. A vascular surgeon performed an abdominal aortic ultrasound scan at four sites using the leading edge to leading edge method. CVD risk score was computed using the ESC-SCORE algorithm. The age and gender specific prevalence was estimated, stratifying by the presence of CVD and cardiovascular risk factors. RESULTS: Among the 3755 subjects with a valid ultrasound measurement, 63 subjects with an AAA were identified (5 referred for surgical intervention), among whom 34 were not previously known (30 men 1.3%, 95% CI 0.9-1.8; 4 women 0.3%, 95% CI 0.1-0.8). Considering age classes in men only, the highest prevalence of screen detected AAA was found in subjects aged 65-70 (1.2%; 95% CI 0.4-2.5) and 70-75 (2.5%; 95% CI 1.4-4.0) years. Among 65-75 year old men, the highest AAA prevalence was found in subjects with a previous myocardial infarction (MI 4.9%, 95% CI 2.0-9.9) and in ever-smokers reporting more than 15 pack years of smoking (4.1%, 95% CI 2.5-6.3). Among the younger subjects, those having an ESC-SCORE higher than 5% or a previous CVD (MI or stroke) showed a prevalence of 1.4% (95% CI 0.3-4.2; prevalence including subaneurysms 6.7%, 95% CI 3.7-11.0%). CONCLUSIONS: In the study population, both a general screening program in 65-75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50-64 year old men, strategies for population selection should consider CVD risk stratification tools.

Determinants of social inequalities in stroke incidence across Europe: a collaborative analysis of 126 635 individuals from 48 cohort studies.

BACKGROUND: Knowledge on the origins of the social gradient in stroke incidence in different populations is limited. This study aims to estimate the burden of educational class inequalities in stroke incidence and to assess the contribution of risk factors in determining these inequalities across Europe. MATERIALS AND METHODS: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) Study comprises 48 cohorts recruited mostly in the 1980s and 1990s in four European regions using standardised procedures for baseline risk factor assessment and fatal and non-fatal stroke ascertainment and adjudication during follow-up. Among the 126 635 middle-aged participants, initially free of cardiovascular diseases, generating 3788 first stroke events during a median follow-up of 10 years, we estimated differences in stroke rates and HRs for the least versus the most educated individuals. RESULTS: Compared with their most educated counterparts, the overall age-adjusted excess hazard for stroke was 1.54 (95% CI 1.25 to 1.91) and 1.41 (95% CI 1.16 to 1.71) in least educated men and women, respectively, with little heterogeneity across populations. Educational class inequalities accounted for 86-413 and 78-156 additional stroke events per 100 000 person-years in the least compared with most educated men and women, respectively. The additional events were equivalent to 47%-130% and 40%-89% of the average incidence rates. Inequalities in risk factors accounted for 45%-70% of the social gap in incidence in the Nordic countries, the UK and Lithuania-Kaunas (men), but for no more than 17% in Central and South Europe. The major contributors were cigarette smoking, alcohol intake and body mass index. CONCLUSIONS: Social inequalities in stroke incidence contribute substantially to the disease rates in Europe. Healthier lifestyles in the most disadvantaged individuals should have a prominent impact in reducing both inequalities and the stroke burden.

Job strain and the incidence of coronary heart diseases: does the association differ among occupational classes? A contribution from a pooled analysis of Northern Italian cohorts.

OBJECTIVES: To assess the association between job strain (JS) and the incidence of coronary heart disease (CHD) in North Italian employed men, adopting a stratified analysis by occupational class (OC). METHODS: The study was conducted on 4103 working men, CHD-free at baseline, enrolled in population-based and factory-based cohorts. Risk factor measurements and follow-up procedures were carried out adopting the WHO MONICA standardised procedures. OCs were derived from the Erikson-Goldthorpe-Portocarero classification. JS categories were defined based on overall sample medians of psychological job demand (PJD) and decision latitude (DL) derived from items of the Job Content Questionnaire, satisfying construct validity criteria. Age-adjusted and risk factors-adjusted CHD HRs were estimated from Cox models, contrasting high-strain (high PJD and low DL) versus non-high-strain categories. RESULTS: In a median follow-up of 14.6 years, 172 CHD events occurred, corresponding to a CHD incidence rate of 2.78/1000 person-years. In the overall sample, high-strain compared with non-high-strain workers evidenced a 39% excess CHD risk, not statistically significant. No association was found among managers and proprietors. Conversely, the HR of high strain versus non-high strain was 1.78 (95% CI 1.20 to 2.66) among non-manual and manual workers, with no substantial differences between them. The exclusion of the events occurring in the first 3 years of follow-up did not change the results. Adopting the quadrant-term JS groupings, among manual and non-manual workers, high-strain and active (high PJD and high DL) categories in comparison to the low strain one (low PJD and high DL) showed HRs of 2.92 and 2.47, respectively. CONCLUSIONS: Our findings support the association of JS and CHD incidence among manual and non-manual workers. The non-high strain may not be the best reference category, when assessing the contribution of JS in determining CHD incidence.

Combined effect of educational status and cardiovascular risk factors on the incidence of coronary heart disease and stroke in European cohorts: Implications for prevention.

Background The combined effect of social status and risk factors on the absolute risk of cardiovascular disease has been insufficiently investigated, but results provide guidance on who could benefit most through prevention. Methods We followed 77,918 cardiovascular disease-free individuals aged 35-74 years at baseline, from 38 cohorts covering Nordic and Baltic countries, the UK and Central Europe, for a median of 12 years. Using Fine-Gray models in a competing-risks framework we estimated the effect of the interaction of education with smoking, blood pressure and body weight on the cumulative risk of incident acute coronary heart disease and stroke. Results Compared with more educated smokers, the less educated had an added increase in absolute risk of cardiovascular disease of 3.1% (95% confidence interval + 0.1%, +6.2%) in men and of 1.5% (-1.9%, +5.0%) in women, consistent across smoking categories. Conversely, the interaction was negative for overweight: -2.6% (95% CI: -5.6%, +0.3%) and obese: -3.6% (-7.6%, +0.4%) men, suggesting that the more educated would benefit more from the same reduction in body weight. A weaker interaction was observed for body weight in women, and for blood pressure in both genders. Less educated men and women with a cluster of two or more risk factors had an added cardiovascular disease risk of 3.6% (+0.1%, +7.0%) and of 2.6% (-0.5%, +5.6%), respectively, compared with their more educated counterparts. Conclusions Socially disadvantaged subjects have more to gain from lifestyle and blood pressure modification, hopefully reducing both their risk and also social inequality in disease.

Descriptive Epidemiology of Somatising Tendency: Findings from the CUPID Study.

Somatising tendency, defined as a predisposition to worry about common somatic symptoms, is importantly associated with various aspects of health and health-related behaviour, including musculoskeletal pain and associated disability. To explore its epidemiological characteristics, and how it can be specified most efficiently, we analysed data from an international longitudinal study. A baseline questionnaire, which included questions from the Brief Symptom Inventory about seven common symptoms, was completed by 12,072 participants aged 20-59 from 46 occupational groups in 18 countries (response rate 70%). The seven symptoms were all mutually associated (odds ratios for pairwise associations 3.4 to 9.3), and each contributed to a measure of somatising tendency that exhibited an exposure-response relationship both with multi-site pain (prevalence rate ratios up to six), and also with sickness absence for non-musculoskeletal reasons. In most participants, the level of somatising tendency was little changed when reassessed after a mean interval of 14 months (75% having a change of 0 or 1 in their symptom count), although the specific symptoms reported at follow-up often differed from those at baseline. Somatising tendency was more common in women than men, especially at older ages, and varied markedly across the 46 occupational groups studied, with higher rates in South and Central America. It was weakly associated with smoking, but not with level of education. Our study supports the use of questions from the Brief Symptom Inventory as a method for measuring somatising tendency, and suggests that in adults of working age, it is a fairly stable trait.

Educational class inequalities in the incidence of coronary heart disease in Europe.

OBJECTIVE: To estimate the burden of social inequalities in coronary heart disease (CHD) and to identify their major determinants in 15 European populations. METHODS: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) study comprised 49 cohorts of middle-aged European adults free of CHD (110 928 individuals) recruited mostly in the mid-1980s and 1990s, with comparable assessment of baseline risk and follow-up procedures. We derived three educational classes accounting for birth cohorts and used regression-based inequality measures of absolute differences in CHD rates and HRs (ie, Relative Index of Inequality, RII) for the least versus the most educated individuals. RESULTS: N=6522 first CHD events occurred during a median follow-up of 12 years. Educational class inequalities accounted for 343 and 170 additional CHD events per 100 000 person-years in the least educated men and women compared with the most educated, respectively. These figures corresponded to 48% and 71% of the average event rates in each gender group. Inequalities in CHD mortality were mainly driven by incidence in the Nordic countries, Scotland and Lithuania, and by 28-day case-fatality in the remaining central/South European populations. The pooled RIIs were 1.6 (95% CI 1.4 to 1.8) in men and 2.0 (1.7 to 2.4) in women, consistently across population. Risk factors accounted for a third of inequalities in CHD incidence; smoking was the major mediator in men, and High-Density-Lipoprotein (HDL) cholesterol in women. CONCLUSIONS: Social inequalities in CHD are still widespread in Europe. Since the major determinants of inequalities followed geographical and gender-specific patterns, European-level interventions should be tailored across different European regions.

Prolonged job strain reduces time-domain heart rate variability on both working and resting days among cardiovascular-susceptible nurses.

INTRODUCTION: Modifications of hearth rate variability (HRV) constitute a marker of the autonomic nervous system (ANS) deregulation, a promising pathway linking job strain (JS) and cardiovascular diseases (CVD). The study objective is to assess whether exposures to recent and prolonged JS reduce time-domain HRV parameters on working days (WD) among CVD-susceptible nurses and whether the association also persists on resting days (RD). MATERIAL AND METHODS: 313 healthy nurses were investigated twice with one year interval to assess JS based on the demand-control and the effort-reward models. 36, 9 and 16 CVD-susceptible nurses were classified as low JS in both surveys (stable low strain - SLS), recent high JS (high JS at the second screening only-RHS) and prolonged high JS (high strain in both surveys-PHS), respectively. In 9, 7 and 10 of them, free from comorbidities/treatments interfering with HRV, two 24-h ECG recordings were performed on WD and RD. Differences in the time domain HRV metrics among JS categories were assessed using ANCOVA, adjusted for age and smoking. RESULTS: In the entire sample (mean age: 39 years, 83% females) the prevalence of high job strain was 38.7% in the second survey. SDNN (standard deviation of all normal RR intervals) on WD significantly declined among JS categories (p = 0.02), with geometric mean values of 169.1, 145.3 and 128.9 ms in SLS, RHS, PHS, respectively. In the PHS group, SDNN remained lower on RD as compared to the low strain subjects (142.4 vs. 171.1 ms, p = 0.02). Similar findings were found for the SDNN_Index, while SDANN (standard deviation of average RR intervals in all 5 min segments of registration) mean values reduced in the PHS group during WD only. CONCLUSIONS: Our findings suggest that persistent JS lowers HRV time-domain parameters, supporting the hypothesis that the ANS disorders may play an intermediate role in the relationship between work stress and CVD.

Measures of abdominal adiposity and the risk of stroke: the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study.

BACKGROUND AND PURPOSE: Excess fat accumulates in the subcutaneous and visceral adipose tissue compartments. We tested the hypothesis that indicators of visceral adiposity, namely, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), are better predictors of stroke risk than body mass index (BMI). METHODS: The association of BMI, WC, WHR, and WHtR with stroke was assessed in 31,201 men and 23,516 women, free of vascular disease at baseline, from the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study. During a mean follow-up of 11 years, 1130 strokes were recorded. Relative risks (95% CI) were calculated by Cox regression after stratification for center and adjustment for age, smoking, educational level, alcohol consumption, hypertension, diabetes, total cholesterol, high-density lipoprotein cholesterol, and BMI and model fit was assessed using log-likelihoods. RESULTS: BMI, WC, WHR, and WHtR were associated with the risk of stroke in men. After full adjustment including BMI, the relative risks for stroke remained significant for WC (1.19 [1.02 to 1.34] per 1 SD increase in WC), WHR (1.14 [1.03 to 1.26]), and WHtR (1.50 [1.28 to 1.77]). Among women, the extent of the associations with stroke risk was similar for WHtR (1.31 [1.04 to 1.65]), WC (1.19 [0.96 to 1.47]), and WHR (1.08 [0.97 to 1.22]). Further analyses by World Health Organization obesity categories showed that WC, WHR, and WHtR were associated with the risk of stroke also in lean men and women (BMI<25 kg/m2), independently of confounders, cardiovascular risk factors, and BMI. CONCLUSIONS: Indicators of abdominal adiposity, especially WHtR, are more strongly associated with stroke risk than BMI. These results emphasize the importance of measuring abdominal adiposity, especially in lean subjects.

The contribution of major risk factors and job strain to occupational class differences in coronary heart disease incidence: the MONICA Brianza and PAMELA population-based cohorts.

OBJECTIVES: We investigated the contribution of major coronary heart disease (CHD) risk factors and job strain to occupational class differences in CHD incidence in a pooled-cohort prospective study in northern Italy. METHODS: 2964 men aged 25-74 from four northern Italian population-based cohorts were investigated at baseline and followed for first fatal or non-fatal CHD event (171 events). Standardised procedures were used for baseline risk factor measurements, follow-up and validation of CHD events. Four occupational classes were derived from the Erikson-Goldthorpe-Portocarero social class scheme: higher and lower professionals and administrators, non-manual workers, skilled and unskilled manual workers, and the self-employed. HRs were estimated with Cox models. RESULTS: Among CHD-free subjects, with non-manual workers as the reference group, age-adjusted excess risks were found for professionals and administrators (+84%, p=0.02), the self-employed (+72%, p=0.04) and manual workers (+63%, p=0.04). The relationship was consistent across different CHD diagnostic categories. Adjusting for major risk factors only slightly reduced the reported excess risks. In a sub-sample of currently employed subjects, adjusting for major risk factors, sport physical activity and job strain reduced the excess risk for manual workers (relative change = -71.4%) but did not substantially modify the excess risks of professionals and administrators and the self-employed. CONCLUSIONS: In our study, we found higher CHD incidence rates for manual workers, professionals and administrators, and the self-employed, compared to non-manual workers. When the entire spectrum of job categories is considered, the job strain model helped explain the CHD excess risk for manual workers but not for other occupational classes.

Gender differences in the association between education and the incidence of cardiovascular events in Northern Italy.

BACKGROUND: The educational differences in the incidence of major cardiovascular events are under-studied in Southern Europe and among women. METHODS: The study sample includes n = 5084 participants to 4 population-based Northern Italian cohorts, aged 35-74 at baseline and with no previous cardiovascular events. The follow-up to ascertain the first onset of coronary heart disease (CHD) or ischaemic stroke ended in 2002. At baseline, major cardiovascular risk factors were investigated adopting the standardized MONICA procedures. Two educational classes were obtained from years of schooling. Age- and risk factors-adjusted hazard ratios of first CHD or ischaemic stroke were estimated through sex-specific separate Cox models (high education as reference). RESULTS: Median follow-up time was 12 years. Event rates were 6.38 (CHD) and 2.12 (ischaemic stroke) per 1000 person-years in men; and 1.59 and 0.94 in women. In men, low education was associated with higher mean Body Mass Index and prevalence of diabetes and cigarette smokers; but also with higher HDL cholesterol and a more favourable alcohol intake pattern. Less-educated women had higher mean systolic blood pressure, Body Mass Index and HDL cholesterol and were more likely to have diabetes. Men and women in the low educational class had a 2-fold increase in ischaemic stroke and CHD incidence, respectively, after controlling for major risk factors. Education was not associated with CHD incidence in men. Higher ischaemic stroke rates were observed among more educated women. CONCLUSION: In this northern Italian population, the association between education and cardiovascular risk seems to vary by gender.