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Recent evidences have shown that phenolic structures can exert many biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. In this study we aimed to investigate the effect of EA on cardiac Ca2+ currents and contractility in rat ventricular myocytes and to elucidate the underlying mechanisms of these changes.All records measured from the freshly isolated ventricular myocytes of rat heart at 36±1 °C by using whole-cell configuration of voltage clamp. Cell shortening was measured by detecting the length of edges with video-based system at 1 Hz frequency of field stimulation. We found that EA dose dependently reduced Ca2+ currents with EC50= 23 nM. EA decreased voltage dependent L-type Ca2+ current density (ICaL) but it didn't affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase (AC) with SQ-22536 (10 μM) and using probucol (antioxidant, 5 μM) had no effect on EA modulation of ICaL. Interestingly, blockage of nitric oxide synthase (NOS) with L-NAME (500 μM) and guanylate cyclase (GC) with ODQ (1 μM) abolished inhibitory effect of EA on ICaL. Moreover, EA dose dependently blunted fractional shorthening of ventricular myocytes.In conclusion, EA affects ionic and mechanical properties of ventricular myocytes starting at nanomolar concentrations. Our findings indicated that EA suppresses ICaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathway. Accordingly, EA may be useful in pathophysiological conditions whereby these effects might be favorable such as hypertension and ischemic heart diseases. [ABSTRACT FROM PUBLISHER]

Background: There are few long-term mortality prediction studies after acute aortic dissection (AAD) Type A and none were performed using new models such as neural networks (NN) or support vector machines (SVM) which may show a higher discriminatory potency than standard multivariable models.Methods: We used 32 risk factors identified by Literature search and previously assessed in short-term outcome investigations. Models were trained (50%) and validated (50%) on 2 random samples from a consecutive 235-patient cohort. NN were run only on patients with complete data for all included variables (N = 211); SVM on the overall group. Discrimination was assessed by receiver operating characteristic area under the curve (AUC) and Gini's coefficients along with classification performance.Results: There were 84 deaths (36%) occurring at 564 +/- 48 days (95%CI from 470 to 658 days). Patients with complete variables had a slightly lower death rate (60 of 211, 28%). NN classified 44 of 60 (73%) dead patients and 147 of 151 (97%) long-term survivors using 5 covariates: immediate post-operative chronic renal failure, circulatory arrest time, the type of surgery on ascending aorta plus hemi-arch, extracorporeal circulation time and the presence of Marfan habitus. Global accuracies of training and validation NN were excellent with AUC respectively 0.871 and 0.870 but classification errors were high among patients who died. Training SVM, using a larger number of covariates, showed no false negative or false positive cases among 118 randomly selected patients (error = 0%, AUC 1.0) whereas validation SVM, among 117 patients, provided 5 false negative and 11 false positive cases (error = 22%, AUC 0.821, p < 0.01 versus NN results). An html file was produced to adopt and manipulate the selected parameters for practical predictive purposes.Conclusions: Both NN and SVM accurately selected a few operative and immediate post-operative factors and the Marfan habitus as long-term mortality predictors in AAD Type A. Although these factors were not new per se, their combination may be used in practice to index death risk post-operatively with good accuracy. [ABSTRACT FROM AUTHOR]

We describe for the first time transthoracic Doppler ultrasound assessment of coronary flow reserve (CFR) in both the posterior descending (PDA) and left anterior descending (LAD) coronary arteries. CFR (hyperemic/resting diastolic flow velocity ratio) was measured by 90-second intravenous adenosine infusion (140 microg/kg/min). Baseline PDA flow was detected in 62 of 81 subjects (76%), and the CFR was measurable in 44 of them (54%) because of adenosine-induced hyperventilation. According to angiography, these 44 subjects were divided into 3 groups: group 1 (0% to 29% stenosis), group 2 (30% to 69% stenosis), and group 3 (> or =70% stenosis). PDA CFR was 2.62 +/- 0.25 in 17 patients in group 1, 2.33 +/- 0.32 in 9 patients in group 2, and 1.40 +/- 0.54 in 18 patients in group 3 (F = 41.83, p <0.0001). LAD CFR was 3.31 +/- 0.54 in 15 patients in group 1, 2.49 +/- 0.71 in 10 patients in group 2, and 1.12 +/- 0.49 in 19 patients in group 3 (F = 65.68, p <0.0001). A cut-off of <2 identified > or =70% stenosis in both of the arteries supplying the PDA and in the LAD. Noninvasive measurement of PDA CFR is feasible and may improve with technologic advancement and the use of selective adenosine receptor agonists, thus preventing hyperventilation. [ABSTRACT FROM AUTHOR]

Background: The impact of marital status on cardiovascular disease (CVD) remains controversial in the general population., Aim: The present investigation sought to delineate the association between marital status and long-term major non-fatal and fatal CVD, along with all-cause mortality within the scope of the RIFLE project (Risk Factors and Life Expectancy)., Methods: We examined the incidences of CVD, including cerebrovascular accidents and coronary heart disease (CHD), as well as all-cause mortality. In total, 47,167 individuals (46% female, average age 50 ± 9 years) were included in the analysis. Marital status at inception was categorized into married (inclusive of married or cohabitating) versus unmarried cohorts (including widowed, separated, divorced, or single individuals)., Results: Compared to their married counterparts, unmarried subjects demonstrated a heightened risk for CVD in both females and males. Throughout a median follow-up span of 7.4 years (interquartile range from 6 to 9 years), married participants, adjusting for standard risk factors, exhibited reduced mortality rates attributed to CHD [hazard ratio (HR) 0.54 (95% confidence interval (CI) 0.33-0.86)) and all causes (HR 0.75 (95% CI 0.62-0.91)] within the aggregate population; this reduction persisted for both CHD-specific [HR 0.39 (95% CI 0.51-0.90)]and all-cause mortality [HR 0.68 (95% CI 0.51-0.90)], independent of traditional risk factors in women. No associations were evident between matrimonial status and any measured outcomes in males., Conclusions: Within primary care settings, marital status should be considered a potential correlate of long-term CHD and overall mortality risks, especially among women., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Aims: A study of the power of physical activity (Phyac) and physical fitness (Fitscore) in predicting very long-term all-cause mortality and age at death (AD) is missing., Methods and Results: A total of 5482 middle-aged men were examined with measurement of several risk factors and followed for 60 years until the virtual extinction of cohorts. Phyac in three classes was estimated from their type of work while Fitscore was derived from the linear combinations of levels of arm circumference, heart rate, and vital capacity computed as a factor score by principal components analysis. The predictive power of these characteristics (adjusted for five traditional cardiovascular risk factors) was made by Cox models (for all-cause mortality) and multiple linear regression models (for AD). Single levels of the three indicators of fitness were highly related to the three levels of Phyac and of Fitscore. High levels of both Phyac and of Fitscore forced into the same models were associated with lower all-cause mortality and higher AD. The predictive power of Fitscore was systematically better than that of Phyac. Hazard ratios (high vs. low) for all-cause mortality were 0.85 (Phyac) and 0.70 (Fitscore). The coefficients (all significant) were 2.25 years (Phyac) and 3.79 of AD by Fitscore. Fitscore was independently and significantly predictive of all-cause mortality for both the first and second 30-year follow-up periods., Conclusion: Phyac and Fitscore are related, and both showed important predictive power for all-cause mortality and AD. The role of Fitscore was more powerful, and both characteristics seem to be expressions of health status., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. 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 and Aim: To study the relationships of an Atherogenicity Index (ATI) and a Thrombogenicity Index (THI), with 50-year mortality from coronary heart disease (CHD), other heart diseases of uncertain etiology (HDUE) and cerebrovascular disease or stroke (STR), in 16 international cohorts of middle-aged men., Methods and Results: Foods from a dietary survey in subsamples of men in each cohort of the Seven Countries Study (SCS) were chemically analyzed for several types of fatty acids that were converted into ATI and THI identifying each of 16 cohorts. Ecological correlations of the ATI and THI were calculated with the three fatal CVD conditions and with all-cause mortality at 25 and 50 years. Correlation coefficients (Rs) were positive and highly significant between ATI and THI versus CHD mortality, with levels ranging from 0.79 to 0.97, depending on the duration of follow-up and the choice of 10 or of 16 cohorts. This was not the case for HDUE and STR mortality for which Rs were variable and not significant. A strong direct association was also found with all-causes deaths at 25 and 50-years. ATI and THI were also directly related with dietary saturated fat and cholesterol levels and inversely with the Mediterranean Adequacy Index (a score identifying the Mediterranean diet)., Conclusion: These findings indicate that CHD has a different relationship with dietary lipids intake than HDUE and STR. This suggests that HDUE and STR have different underlying pathways or are different diseases., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aim: During the last few years, the Seven Countries Study of Cardiovascular Diseases (SCS) produced some new analyses dealing with the relationships of a dietary score, the pool of dietary fatty acids and serum cholesterol with major types of cardiovascular disease (CVD) mortality in 10 cohorts of 6 countries made of middle-aged men followed-up for 60 years until extinction. This sparse evidence is condensed here to provide a coherent view., Methods and Results: The Mediterranean Adequacy Index (MAI, a dietary score whose high levels depict the characteristics of the Mediterranean Diet), was highly and significantly associated in an inverse way, at country levels, with the Atherogenicity (ATI) and the Thrombogenicity (THI) indexes that included a series of dietary fatty acids. These indexes were highly and significantly associated in a direct way with country baseline serum cholesterol levels. Countries with high serum cholesterol had largely higher death rates from coronary heart disease (CHD) and lower rates from other heart diseases of uncertain etiology and stroke. The reverse was observed in countries with low serum cholesterol., Conclusion: The chain of diet, dietary fatty acids and serum cholesterol seems to be responsible in various ways for the different distribution of major CVD mortality subtypes in extincted cohorts., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest. The authors certify that they complied with the Principles of Ethical Publishing Rules., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. All rights reserved.)

Background and Aim: To study the relationships of cardiovascular risk factors with cancer and cardiovascular mortality in a cohort of middle-aged men followed-up for 61 years., Materials and Methods: A rural cohort of 1611 cancer- and cardiovascular disease-free men aged 40-59 years was examined in 1960 within the Italian Section of the Seven Countries Study, and 28 risk factors measured at baseline were used to predict cancer ( n = 459) and cardiovascular deaths ( n = 678) that occurred during 61 years of follow-up until the extinction of the cohort with Cox proportional hazard models., Results: A model with 28 risk factors and cancer deaths as the end-point produced eight statistically significant coefficients for age, smoking habits, mother early death, corneal arcus, xanthelasma and diabetes directly related to events, and arm circumference and healthy diet inversely related. In the corresponding models for major cardiovascular diseases and their subgroups, only the coefficients of age and smoking habits were significant among those found for cancer deaths, to which healthy diet can be added if considering coronary heart disease alone. Following a competing risks analysis by the Fine-Gray method, risk factors significantly common to both conditions were only age, smoking, and xanthelasma., Conclusions: A sizeable number of traditional cardiovascular risk factors were not predictors of cancer death in a middle-aged male cohort followed-up until extinction.

Objective: To study possible determinants of longevity in a cohort of middle-aged men followed for 61 years until extinction using measurements taken at baseline and at years 31 or 61 of follow-up., Material and Methods: In 1960, two rural cohorts including a total of 1712 men aged 40-59 years were enrolled within the Italian section of the Seven Countries Study of Cardiovascular Diseases, and measurements related to mainly cardiovascular risk factors, lifestyle behaviors, and chronic diseases were taken at year 0 and year 31 of follow-up (when only 390 could be examined). Multiple linear regression models were computed to relate personal characteristics with the length of survival in both dead men and survivors., Results: Baseline cardiovascular risk factors, smoking and dietary habits, and chronic diseases (taken at year 0 with men aged 40-59 years) were significant predictors of the length of survival both from year 0 to year 31 and from year 0 to year 61, but only chronic diseases were independent predictors for the period of 31 to 61 years. Significant predictors of survival using measurements taken at year 31 (age range 71 to 90 years) were only smoking and dietary habits and chronic diseases., Conclusions: During a lifetime of follow-up, the personal characteristics with continuous predictive power of survival were only lifestyle behaviors and major chronic diseases.

Background: White coat effect (WCE) and white coat hypertension (WCH) are hardly both compared in primary care., Objective: To assess the usefulness of repeated measures of systolic blood pressure (SBP) to dissociate various forms of white-coat interactions., Methods: An open cross-sectional study on consecutive patients treated or not for high blood pressure was made in family physicians' offices. SBP was measured 5 times by an electronic device. Measurements were performed before (SBP1) and after (SBP5) the office visit by a lay assistant and at the beginning (SBP2), middle (SBP3) and end (SBP4) of visit, by the family physician. Home BP (HBPM) was measured from 3 consecutive days by the patient. WCE and office WCE tail (OWCET) were defined, respectively, as a 10 mmHg SBP increase or decrease between SBP2-SBP1 or SBP4-SBP2. WCH was considered when HBPM was normal (SBP < 135 mmHg) at home and high during the SBP2 office visit., Results: Two hundred five patients (134 women versus 71 men, ratio 1.9, aged 59.8±15.7 years) were recruited. In categorical terms, there were 51 patients (25%) who presented with WCE, OWCET was seen in 121 patients (62%) and 47 patients (23%) had WCH. Only 36 patients (18%) presented both OWCET and WCE and 32 (16%) had both OWCET and WCH. The receiver operating characteristic curves (ROCs) of OWCET in diagnosing WCE or WCH were respectively 0.67 (p<0.0001) and 0.53 (NS)., Conclusion: Thus, OWCET was predictive of WCE and not of WCH and it is worthwhile to be measured in the family physician office., Competing Interests: Declaration of competing interest The Authors declare that they have no conflict of interest to disclose. This work was carried out as part of a PhD thesis at the University of Caen Normandy (France)., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: To study a male Italian cohort (initially aged 40-59, n = 1712) during 61 years and the natural history of major CVD mortality categories including coronary heart disease (CHD), stroke and other heart diseases of uncertain etiology (HDUE), including congestive heart failure) along with their risk factor relationships., Methods and Results: Cox models were run with 12 covariates as possible predictors measured at entry to the study. About 93% of all CVD deaths were covered by the three major groups selected here (N = 751): 37.4% of them were diagnosed as CHD, 30.6% as stroke and 28.5% as HDUE. CHD declined in the last 20 years of follow-up, while a sharp increase in HDUE mortality was seen. Baseline mean levels of serum cholesterol were 209.6, 204.2 and 198.0 mg/dL, respectively, for CHD, stroke and HDUE deaths: the multivariable coefficients of serum cholesterol were positive and significant for CHD ( p < 0.0001), and stroke ( p = 0.0203) and not significant for HDUE ( p = 0.3467). In Fine-Gray models, the algebraic signs of cholesterol coefficients were opposite for CHD versus the other mortality categories (t = 3.13). The predictive performances of remaining risk factors were varied whereas that of Cox models was not very good, probably due to the attrition phenomenon and possible competing risks., Conclusion: Large differences in natural history and risk factors were found comparing the three CVD conditions, potentially indicating different etiologies and pointing to the need of not mixing them up in a grouped CVD category.

Based mainly on their personal experience, the authors try to describe the origin of cardiovascular disease (CVD) epidemiology and the problems and difficulties practitioners attempted to tackle and solve during the first few decades of this discipline, which started around the middle of the last century. Beyond identifying the characteristics of those who became CVD epidemiologists, a description is given of the initial structures of the involved studies, participation rates, risk factors measurements and standardization, clinical measurements and diagnostic criteria, mortality data collection and coding, data loading and analysis, plus a number of problems still unsolved at the beginning of the 2000s. Despite many obstacles, and the initial hostility of the medical-scientific establishment, CVD epidemiology represented a revolution in researching in the bio-medical field. In the end, it also affected clinical research introducing the use of the quantitative approach bound to mathematical-statistical procedures. After decades of hard work and the development of a number of innovative tools, CVD epidemiology received its deserved recognition, eventually being accepted as a reputable and independent scientific discipline. Yet, in several countries, especially those from Southern Europe, an academic recognition of CVD epidemiology is still lacking.

Objectives: To assess whether competing risks help explain why regions with initially high serum cholesterol have higher mortality from coronary heart disease (CHD) and lower mortality from stroke and other major heart diseases, while the reverse is found for those with initially lower serum cholesterol., Material and Methods: Ten cohorts of men (N = 9063) initially aged 40-59 in six countries were examined and followed for fatal outcomes for 60 years. Major cardiovascular disease (CVD) groups were CHD, stroke, and other Heart Diseases of Uncertain Etiology (HDUE), or the combination of stroke and HDUE (STHD), along with all other causes of death. Fine-Gray competing risk analysis was applied with CHD versus all other causes of death or STHD (direct mode) and all other causes of death or STHD versus CHD (inverse mode), and the effects of 19 covariates (of which 3 references) on the cause-specific hazard of the outcomes were assessed, thus investigating potential etiologic roles. A systematic comparison with results obtained by running the Cox model in direct and inverse modes with the same end-point results was also performed and illustrated graphically., Results: CHD mortality is bound to different risk factor relationships when compared with all other causes of death and with STHD. The role of serum cholesterol is crucial since, in both comparisons, by Fine-Gray, its coefficients are positive and significant for CHD and negative and significant for all other causes of death and STHD. Risk factor capabilities in specific outcome types of the CVD domain (CHD versus STHD) are different depending on the outcome types considered. Risk factor coefficients are smaller in Fine-Gray modelling and larger in the Cox model. Fine-Gray detects different risk factors whose coefficients may have opposite algebraic signs., Conclusions: This is the first report whereby a large group of risk factors are investigated in connection with life-long CVD outcomes by Fine-Gray competing risk analysis, and a systematic comparison is performed with results obtained by Cox models in both direct and inverse modes. Subtypes of CVD mortality should be summed with full awareness that some risk factors vary by pathology, and they should at least be disentangled into CHD and STHD.

Background: Hypertension (HTN) is a well-established and a major risk factor for cardiovascular disease. Lifestyle behaviours for its prevention and control are recommended within worldwide guidelines. Their relationship with HTN need more investigations., Aim: We aimed to investigate the associations between lifestyle, anthropometric and biological measurements and BP in the Gubbio residential study., Methods: Cross-sectional analyses were performed using data from Gubbio study. Information concerning lifestyle factors were collected using self-reported questionnaire and were further completed with a baseline clinical examination and blood exams. Three BP measurements were performed following a standard protocol. Age-adjusted and multivariable logistic regressions were used to examine the relationships between lifestyle parameters and HTN separately for each sex. We used heterogeneity test to observe sex differences., Results: There were 3,183 persons included (48% men, 43 ± 17 years old). Mean systolic BP (SBP) was 119 ± 16 mmHg and 10.6% were hypertensives. Age [OR: 129.70 (95%CI: 18.57-905.79) in women and OR: 8.37 (95%CI: 4.01-17.48) ( p  < 0.0001) in men] and BMI [OR: 2.14 (95%CI: 1.32-3.46) ( p  = 0.006) in women and OR: 1.81 (95%CI: 1.05-3.12), p  = 0.03 in men], were positively associated with SBP in both sexes. Serum uric acid [OR: 3.86 (95%CI: 2.03-7.26), p  = 0.04] was positively associated with HTN in women while fasting blood glucose [OR: 3.04 (95%CI: 1.55-5.97), p  < 0.001] were associated to HTN only in men., Discussion: In addition to age, BMI is associated with HTN in both sexes while sex differences were observed in the associations between serum uric acid, fasting blood glucose and HTN.

To study lifetime relationships of three major lifestyle behaviours with cardiovascular mortality in a cohort of middle-aged men that reached practical extinction. In the Italian Areas of the Seven Countries Study of Cardiovascular Diseases (SCS), 1712 men were enrolled and examined in 1960, and behavioural habits were measured: smoking habits, physical activity and diet each divided into three classes. Follow-up for mortality was extended for 61 years. Three groups of major cardiovascular diseases (CVD) were used for analysis, coronary heart disease (CHD), STROKE and other Heart Diseases of Uncertain Aetiology (HDUE). Kaplan-Meier curves, death rates in classes of behaviours and Cox proportional hazard models were computed, the last ones adjusted for other major risk factors.In 61 years of follow-up, 1708 men died and 727 were cases of CVD as defined above. Clear separation of classes in Kaplan-Meier survival curves were seen only for physical activity and diet in CHD, and physical activity for STROKE. Cox proportional hazard ratios (HR, adjusted for age, blood pressure and serum cholesterol) showed the significant protective effect on CHD of Mediterranean diet (HR = 0.72), vigorous physical activity (0.55), never smoking (0.73); on STROKE of vigorous physical activity (0.67); on HDUE of never smoking (0.57). Combination of three healthy versus three unhealthy behaviours was associated for CHD to a lower mortality of 39%. This comparison was not coherent for STROKE and HDUE.Lifetime healthy behaviours are clearly beneficial versus CHD mortality but not necessarily for mortality from HDUE and STROKE that probably represent different morbid conditions.

Age at death (AD) is an old metric recently re-evaluated for the study of longevity and mainly used in demography. Developed experience using AD in field epidemiology is summarized with cohorts followed-up for variable periods of time, frequently until extinction or close to extinction, a must to correctly adopt this metric. For practical purposes, a small number of examples is reported condensing previously published results to highlight various aspects of the problem. AD became the alternative of overall death rates when comparing cohorts reaching extinction or near extinction. AD was useful to characterize different causes of death in order to describe their natural history and possible etiology. With the use of multiple linear regression, a large number of possible determinants of AD were identified and some combinations of them resulted in large estimated differences in AD of 10 years or more across individuals. AD is a powerful tool to study population samples followed-up until extinction or near extinction. It allows to compare the life-long experience of different populations, to compare the role of different causes of death and to study the determinants of AD that are conditioning longevity., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To investigate mortalities from three major groups of cardiovascular diseases (CVDs) in a pooled cohort and followed up until extinction., Materials and Methods: Ten cohorts of men ( N = 9063) initially aged 40-59, in six countries, were examined and followed-up for 60 years. The major CVD groups were coronary heart disease (CHD), cerebrovascular diseases (STROKE) and other heart diseases of uncertain etiology (HDUE)., Results: Death rates from CHD were higher in countries with high serum cholesterol levels (USA, Finland and The Netherlands) and lower in countries with low cholesterol levels (Italy, Greece and Japan), but the opposite was observed for STROKE and HDUE, which became the most common CVD mortalities in all countries during the last 20 years of follow-up. Systolic blood pressure and smoking habits were, at an individual level, the common risk factors for the three groups of CVD conditions, while serum cholesterol level was the most common risk factor only for CHD. Overall, death rates for the pooled CVDs were 18% higher in North American and Northern European countries, while CHD rates were 57% higher in the same countries., Conclusions: Differences in lifelong CVD mortalities across different countries were smaller than expected due to the different rates of the three groups of CVD, and the indirect determinant of this seemed to be baseline serum cholesterol levels.

To investigate whether marital status is associated to long-term major fatal and non-fatal cardiovascular events in men and women from the Gubbio Population Study. The incidence of cardiovascular disease (CVD), including stroke and coronary heart disease (CHD) and CVD death together with all-cause mortality were analyzed. The analysis included 2832 persons (44% men, 54 ± 11 years old). Marital status was defined at entry as married (married or living conjugally) versus unmarried subjects (widowed, separated, divorced or single). Married and unmarried subjects did not differ concerning socio-demographic, anthropometric and biological variables at baseline. Over 191 months median follow-up, the incidence of CHD was lower among married versus unmarried women [HR: 0.63 (95% CI 0.41-0.96)] only; the same was true for CHD mortality [HR: 0.43 (95% CI 0.22-0.84)] and all-cause mortality [HR: 0.75 (95% CI 0.59-0.96)] independently of traditional risk factors (age, SBP, total and HDL cholesterol, cigarette smoke and BMI). In men, marital status was not associated to any of the investigated outcomes. In primary care, marital status should be investigated as it can be associated with long-term CHD and all-cause incidence and mortality risks among women., (© 2023. The Author(s).)

Objectives: The aim of this study was to describe and interpret differences in major cardiovascular disease (CVD) mortality during 60 years between Northern European and Southern European cohorts of the Seven Countries Study of Cardiovascular Diseases., Material and Methods: Northern Europe included two cohorts from Finland and one from the Netherlands, and Southern Europe included two cohorts from Italy and two from Greece, for a total of 2360 and 2792 CVD-free men, respectively, at entry examination. Coronary heart disease (CHD), STROKE and other Heart Diseases of Uncertain Etiology (HDUE) deaths were the outcomes and Cox models were solved separately based on 12 risk factors., Results: In 60 years, overall death rates were 99.8% in both Northern and Southern Europe and the pooled CVD rates were 46.9% (significantly higher) and 42.2%, respectively: CHD mortality was higher in Northern Europe, whereas STROKE and HDUE mortality were higher in Southern Europe. Significant Cox coefficients for both areas (but not significantly different between areas) were age, smoking habits, SBP and serum cholesterol for CHD, and only age and SBP did so for STROKE and HDUE. Age at death was lower for CHD, intermediate for STROKE and higher for HDUE in both areas., Conclusion: The advantage for Southern Europe was small in terms of overall CVD death rates, but definitely larger in terms of expectancy of life due to the differences in age at death in the three types of CVD mortality. Mean entry levels of serum cholesterol, 50 mg/dl higher in Northern Europe than in Southern Europe are a major culprit of these outcomes., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Objectives: To study age at death (AD) and its determinants in cohorts of middle-aged men followed-up until extinction., Material and Methods: A total of 9063 middle-aged men enrolled in 10 cohorts of 6 countries (USA, Finland, the Netherlands, Italy, Greece and Japan) within the Seven Countries Study were examined and then followed up for 60 years until extinction. AD was computed and a small number of risk factors were tested through multiple linear regression as possibly related to attained AD., Results: AD ranged across cohorts from 71.8 years in East Finland and 80.5 years in Crete with levels roughly lower in the USA and Northern Europe and higher elsewhere. Across cohorts, the correlation coefficients of systolic blood pressure (R = -0.58) and of CVD prevalence (R = -0.65) versus average AD were the only significant ones. At the individual level in the pool of all cohorts, a multiple linear regression model showed that age, vigorous physical activity, never and ex-smokers were favorably related to AD, while the reverse was true for systolic blood pressure, heart rate, serum cholesterol, CVD prevalence and silent ECG abnormalities. BMI had a parabolic relationship with AD. The predicting power of single risk factors, expressed in years gained or lost, was relatively small, but arbitrary combinations of several of them produced large differences in AD., Conclusions: A small number of CVD risk factors were strongly associated with AD in a life-long follow-up., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The directions of primary strain lines of local deformation in Epicardial and Endocardial layers have been the subject of debate in recent years. Different methods led to different conclusions and a complete assessment of strain direction patterns in large and variable (in terms of pathology) cohorts of healthy and diseased patients is still lacking. Here, we use local deformation tensors in order to evaluate the angle of strain lines with respect to the horizontal circumferential direction in both Epi- and Endo-layers. We evaluated this on a large group of 193 subjects including 82 healthy control and 111 patients belonging to a great variety of pathological conditions. We found that Epicardial strain lines obliquely directed while those of Endocardium are almost circumferential. This result occurs irrespective of pathological condition. We propose that the geometric vinculum characterizing Endocardium and Epicardium in terms of different lever arm length and orientation of muscular fibers during contraction inescapably requires Endocardial strain lines to be circumferentially oriented and this is corroborated by experimental results. Further investigations on transmural structure of myocytes could couple results presented here in order to furnish additional experimental explanations.

Background and Aim: To test a dietary score produced from individual data of middle-aged-men enrolled in 1960 based on an a-posteriori approach and to study its association with some specific causes of death during 61 years until their practical extinction., Methods and Results: In 1960 the Italian Rural Areas of the Seven Countries of Cardiovascular Diseases were enrolled and 1712 men aged 40-59 were examined with measurement of several risk factors and the collection of dietary history. Using 18 food groups a factor score was obtained from a Principal Component Analysis, that was divided into three classes, arbitrarily called non-Mediterranean, Intermediate and Mediterranean diets. Follow-up for mortality was extended for 61 years and dietary habits were related to several causes of death. There were 1708 deaths (99.8%) and Cox proportional hazards models, adjusted for five major risk factors, showed a significant protective effect of Mediterranean diet for coronary heart disease [Hazard Ratio (HR) = 0.67], cancer other than lung (0.74) and other causes, as from an operational definition (0.71), covering overall about 60% of all deaths. HR for all-cause mortality was of 0.85. In parallel, Kaplan-Meier curves provided significant p of log rank test for the same end-points (<0.0001, 0.0002, 0.0002 and < 0.0001, respectively). On the other hand, stroke, heart diseases of uncertain etiology, lung cancer, chronic bronchitis, unknown causes were not associated to dietary habits., Conclusion: In a 61-year follow-up of middle-aged men, the Mediterranean diet was beneficial for a large part of the causes of death and for total mortality., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To study the role of high R waves predicting cardiovascular (CVD) and all-cause mortality in a male middle-aged population followed-up 45 years., Material and Methods: A total of 7985 CVD-free men aged 40-59 years were enrolled in 13 cohorts in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) and high R waves were classified by Minnesota Code 3.1 (as a dichotomous variable) from baseline resting otherwise normal ECG at entry examination together with other personal characteristics. Cox models were solved to detect the possible predictive role of high R waves for CVD and all-cause mortality., Results: In Cox models high R waves were predictive of 45-year major CVD deaths with a hazard ratio of 1.17 (95% confidence intervals of 1.03-1.33) after adjustment for 6 major CVD risk factors (age, systolic blood pressure, serum cholesterol, cigarette smoking, physical activity and body mass index). The predictive role of high R wave was less evident for 45-year all-cause mortality and after adjustment for the 6 covariates the HR of high R wave lost its significance. A multiple logistic model indicated that body mass index, serum cholesterol, systolic blood pressure and mainly vigorous physical activity were directly related to high R wave prevalence while heart rate, subscapular skinfold, laterality index and shoulder pelvis shape did so in an inverse way., Conclusion: High R waves seem associated with an excess CVD mortality in a 45-year follow-up of middle-aged men, while their role is diluted when the end-point is all-cause mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To explore possible determinants of longevity as a function of many personal characteristics in a cohort of middle-aged men followed-up until practical extinction., Materials and Methods: In the Italian Rural Area of the Seven Countries Study, 1712 men aged 40-59 were examined in 1960 and 35 personal characteristics were measured. The subsequent follow-up for life status was of 61 years when only 3 men survived. A Kaplan-Meier curve was computed. A Cox model was solved with all-cause mortality as end-point and 35 potential determinants as covariates. A Multiple Linear Regression (MLR) model was also solved with the same covariates and age at death (AD) as end-point., Results: After 61 years, 99.8% of men had died and median age at death was 75. Beneficial risk factors for both models (p < 0.05) were: never smoker, vigorous physical activity, prudent and Mediterranean diets, arm circumference, subscapular skinfold, and vital capacity. Adverse risk factors (p < 0.05) were: mother early death, laterality/linearity index, systolic blood pressure, serum cholesterol, corneal arcus, xanthelasma, cardiovascular diseases, cancer, diabetes, and chronic bronchitis. Some arbitrary combinations of selected risk factors were used to estimate AD as a function of coefficients of the MLR, showing large differences up to 10 years or more., Conclusions: Several personal characteristics of anthropometric, behavioral, biophysical, biochemical, and clinical nature are strongly associated with longevity when measured in middle-aged men and then followed up until extinction., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)