Marital status and long-term cardiovascular risk in general population (Gubbio, Italy).

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.

Relationship between lifestyle factors and hypertension: a cross-sectional analysis from the Gubbio study.

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.

Dietary habits, cardiovascular and other causes of death in a practically extinct cohort of middle-aged men followed-up for 61 years.

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.

Simple versus complex carbohydrates and health: A frequently neglected problem.

AIMS: For several decades, there has been a notion that dietary fat is made of different components (at least SAFA, MUFA, and PUFA) that exhibit different and sometimes contrasting effects when associated with health and diseases: coronary heart disease (CHD) and cardiovascular diseases (CVD) in general. A similar fact is not noticed in carbohydrates and their components considering that even some major recent studies on the issue did not segregate simple carbohydrates from complex carbohydrates. In this study, we aimed to stress this need. DATA SYNTHESIS: A small number of selected studies are presented and commented where segregation of simple from complex carbohydrates was either performed or disregarded to address the inconsistency of not disentangling them. CONCLUSIONS: If only total fats were considered in investigations where fat was studied, the present notion and attitude toward different roles of the various classes of fats, at least SAFA versus unsaturated (MUFA and PUFA) would be missing. Therefore, there is a need to disentangle simple from complex carbohydrates, and this should be systematically applied when addressing CHD or CVD mortality risks and their preventive measures.

Energy-adjusted Dietary Inflammatory Index scores predict long-term cardiovascular disease mortality and other causes of death in an ecological analysis of the Seven Countries Study.

Using data from the Seven Countries Study of Cardiovascular Diseases, the first study to conduct international comparisons of men in different European, USA, and Japanese cohorts, we examined the effect of diet-associated inflammation on prediction of coronary heart disease-, other major cardiovascular disease- and all-cause mortality after 50-years of follow-up. The energy-adjusted Dietary Inflammatory Index was used to quantify the effect of diet on systemic inflammation. Positive linear correlations were observed between the cohort-average energy-adjusted Dietary Inflammatory Index score and both overall death rates (R = 0.61, p = 0.0114) and major cardiovascular disease mortality rates (R = 0.51, p = 0.0337) but not cancer. Correlations for all-cause mortality were higher when the Belgrade outlier cohort was omitted (R = 0.72, p = 0.0024) or when analyses were adjusted for socioeconomic status (R = 0.67, p = 0.0065). There was also a significant reverse correlation between energy-adjusted Dietary Inflammatory Index score and age at death (R = -0.50 to -0.68, p = 0.0480 to 0.0012). Adjusting for systolic blood pressure, cholesterol, and smoking habits did not modify these correlations that were still significant. With control for these covariates a significant correlation emerged for coronary heart disease. Results obtained using a 25-year follow-up to allow unprojected data from all cohorts were similar. Results from this long-term follow-up study are consistent with a recommendation to increase consuming an anti-inflammatory diet characterized by high concentrations of fruits and vegetables and low consumption of simple carbohydrates and fats.

Impact of Sex on Office White Coat effect Tail: A Review.

Office white-coat effect tail (OWCET) is defined as a decrease of ≥10 mmHg in systolic blood pressure (SBP) between successive measurements after its waxing during an office visit. The influence of sex on the incidence of long-term major fatal and non-fatal cardiovascular events was studied in two Italian populational cohorts [from the Gubbio Study and the Italian Rural Areas of the Seven Countries Study (IRA)]. OWCET increased risk of cardiovascular disease (CVD) [HR: 1.591 (95% CI: 1.204-2.103)], coronary heart disease (CHD) [HR: 1.614 (95% CI: 1.037-2.512)] and stroke (STR) [HR: 1.696 (95% CI: 1.123-2.563)] events independently of age, serum and high density lipoprotein (HDL) cholesterol, cigarettes, body mass index (BMI) and SBP in women included in Gubbio study over an almost 20-year follow-up. However, risks of CVD, CHD or STR increased in men with OWCET neither in the Gubbio 20-year follow-up nor in the IRA 50-year follow-up. The correction of the regression dilutions bias between the first and the subsequent SBP measurements did not significantly change these outcomes. Primary care physicians should evaluate OWCET, especially in women, to improve stratification of long-term CVD, CHD and STR risks.

Association of serum cholesterol with coronary heart disease mortality during 50-year follow-up in ten cohorts of the seven countries study.

BACKGROUND AND AIM: The association of serum cholesterol levels with the occurrence of coronary heart disease (CHD) mortality during a follow-up of 50 years was rarely investigated previously. Thus, we took advantage of results at hand in 10 pooled cohorts of men aged 40-59 years from the Seven Countries Study (9063 individuals and 2057 CHD fatal events) and we assessed this. METHODS AND RESULTS: Cox proportional hazards models were run with CHD fatal events (as dependent variable) and cholesterol levels (as independent variables) at years 0, 10, and 25 (in 5 cohorts). Cumulative events during subsequent decades (cumulative approach: CA) and separately in each subsequent decade (partitioned approach: PA) were analyzed. The ecological correlation of average baseline serum cholesterol levels with CHD mortality was very high (R = 0.97). Serum cholesterol and CHD mortality for 50 years were associated at the individual level, and the association estimated by the Cox's coefficients (and related hazards ratios) was initially strong in both CA and PA, but slightly declined during later decades. Hazards ratios (for a difference of 40 mg/dl) ranged from 1.39 to 1.20 for CA and from 1.39 to 0.80 for PA. Coefficients were larger for CA than for PA and the decline was more evident for the latter. Partitioned coefficient became negative and significant in the last decade (from year 40-50). Coefficients derived from cholesterol levels measured at year 10 of follow-up showed similar trends but their magnitude was smaller. CONCLUSION: Thus, the relationship of serum cholesterol levels with CHD mortality remained relatively stable during at least 40 years after a single cholesterol measurement at baseline in middle-aged men.

Association of patient-reported outcomes and heart rate trends in heart failure: a report from the Chiron project.

Patient-reported outcomes (PROs) have been previously considered "soft" end-points because of the lack of association of the reported outcome to measurable biological parameters. The present study aimed to assess whether electrocardiographic measures are associated to PROs changes. We evaluated the association between heart rate (HR), QRS and QT/QTc durations and PROs, classified as "good" or "bad" according to the patients' overall feeling of health, in patients from the Chiron project. Twenty-four chronic heart failure (HF) patients were enrolled in the study (71% male, mean age 62.9 ± 9.4 years, 42% ischemic etiology, 15 NYHA class II and 9 class III) providing 1086 days of usable physiological recordings (4 hours/day). The mean HR was significantly higher in the "bad" than in the "good" PROs class (74.0 ± 6.4 bpm vs 68.0 ± 7.2 bpm; p < 0.001). Conversely, the ratio between movement and rest activities showed significantly higher values in "good" compared to "bad" PROs. We also found significantly longer QTc and QRS durations in patients with "bad" PROs compared to patients with "good" PROs. That in patients with mild to moderate HF, higher HR, wider QRS and longer QTc, as well as a reduced HR ratio between movement and rest, were associated with "bad" PROs is clinically noteworthy because the association of worse PROs with measurable variations of biological parameters may help physicians in evaluating PROs reliability itself and in their clinical decisions. Whether a timely intervention on these biological parameters may prevent adverse outcomes is important and deserves to be investigated in further studies.

Coronary heart disease mortality trends during 50 years as explained by risk factor changes: The European cohorts of the Seven Countries Study.

OBJECTIVES: The purpose of this study was to relate risk factor changes during decades with 50-year coronary heart disease mortality in European cohorts of middle-aged men of the Seven Countries Study. MATERIAL AND METHODS: In the 1950s-early 1960s, nine cohorts of 6518 men aged 40-59 years were examined in five European countries. Smoking habits, systolic blood pressure and serum cholesterol were measured at entry and five times during the next 35 years and a comprehensive Risk Factor Change Score was created. Coronary heart disease mortality data was collected during a 50-year follow-up, modelled by the Weibull distribution, whose shape (Weibull shape) was related to the Risk Factor Change Score by linear regression. RESULTS: The Risk Factor Change Score showed slight declines in the Finnish and Dutch cohorts, moderate or large increases in the other cohorts. These effects were related to a decrease of smoking habits in all cohorts, an increase of blood pressure in all cohorts except East Finland, a decrease of serum cholesterol in Finland and the Netherlands, whereas serum cholesterol increases were slight in Italy and large in Serbia and Greece. Weibull distribution shape for coronary heart disease mortality showed slight deceleration in one Finnish and the Dutch cohorts, large acceleration in the Serbian and Greek cohorts. The correlation coefficient of the Risk Factor Change Score versus Weibull shape for the nine cohorts was 0.78 (R2 = 0.60; p = 0.0132). CONCLUSIONS: Spontaneous long-term changes of major coronary risk factor levels were associated with changes in the same direction of coronary heart disease mortality risk modelled by the Weibull distribution, expressing a kind of 'natural experiment' with an outcome that matches those of controlled preventive trials.

Local and global energies for shape analysis in medical imaging.

In a previous contribution, a new Riemannian shape space, named TPS space, was introduced to perform statistics on shape data. This space was endowed with a Riemannian metric and a flat connection, with torsion, compatible with the given metric. This connection allows the definition of a Parallel Transport of the deformation compatible with the three-fold decomposition in spherical, deviatoric, and non-affine components. Such a parallel transport also conserves the Γ-energy, strictly related to the total elastic strain energy stored by the body in the original deformation. A new approach is here presented in order to calculate the bending energy on the body alone (body bending energy) and to restrict it exclusively within physical boundaries of objects involved in the deformation analysis. The novelty of this new procedure resides in the fact that we propose a new metric to be preserved during the TPS direct transport. This allows transporting the shape change more coherently with the mechanical meaning of the deformation. The geometry of the TPS space is then further discussed in order to better represent the relationship between the Γ-energy, the strain energy, and the so-called bending energy densities.

How the Seven Countries Study contributed to the launch and development of cardiovascular epidemiology in Italy. A historical perspective.

The Italian research group of the Seven Countries Study of Cardiovascular Diseases (SCS), through the independent use of the national cohorts and data, had the lucky opportunity, starting in the early 1960, to launch the Italian research in epidemiology of cardiovascular diseases (CVD). In this way, the Italian Section of that international study became the first investigation with baseline measurements in various cohorts, subsequent re-examinations, systematic search for morbid events, and follow-up for mortality up to 50 years. A large number of scientific aspects has been tackled including estimates of morbidity and mortality rates, the association of risk factors with cardiovascular events and total mortality, the role of risk factor changes, the use of multivariable models, the role of lifestyle behavior, the determinants of all-cause mortality including risk factors rarely measured in other studies, the identification of characteristics of a condition called Heart Disease of Uncertain Etiology (HDUE), the production of predictive tools for practical use and several other issues. All this has been enhanced by the availability of extremely long follow-up data rarely found in other studies. Field work organization, measurement techniques, diagnostic criteria, data handling and computing had the limitations and difficulties typical of those times, the mid of last century, when CVD epidemiology was at its beginning. All this represented anyhow the start of CVD epidemiology research in the country and was the stimulus to the start of other studies and a valuable collaboration with some of them.

Impact of Sex on Office White Coat Effect Tail: Investigating Two Italian Residential Cohorts.

To assess the impact of sex on office white-coat effect tail (OWCET), the waning of systolic blood pressure (SBP) after its waxing during office visit, on the incidence of long-term major fatal and non-fatal events in two Italian residential cohorts [from the Gubbio Study and the Italian Rural Areas of the Seven Countries Study (IRA)]. There were 3565 persons (92 with missing data, 44% men, 54 ± 11 years) included in the Gubbio and 1712 men (49 ± 5 years) in the IRA studies. OWCET was defined as a decrease of ≥10 mmHg in SBP between successive measurements with slight measurement differences between the two cohorts. Cardiovascular (CVD), coronary heart disease (CHD) and stroke (STR) incidences were considered. Over an approximately 20-year follow-up, women with OWCET had an increased risk of CVD [HR: 1.591 (95%CI: 1.204-2.103)], CHD [HR: 1.614 (95%CI: 1.037-2.512)] and STR [HR: 1.696 (95%CI: 1.123-2.563)] events independently of age, serum and HDL cholesterol, cigarettes, BMI and SBP in the Gubbio study. However, there was no increased risk of CVD, CHD or STR in men with OWCET neither in the Gubbio 20-year follow-up nor in the IRA 50-year follow-up. These results were not modified significantly by the correction of the regression dilutions bias between the first and the subsequent SBP measurements. Thus, in primary care, OWCET should be actively evaluated in women as it can improve stratification of long-term CVD, CHD and STR risks.

Lifestyle and awareness of cholesterol blood levels among 29159 community school children in Italy.

BACKGROUND AND AIM: Lifestyle habits including indoor and outdoor activities among community school children, adherence to the Mediterranean diet and awareness about total cholesterol blood levels represent determinant factors in cardiovascular disease (CVD) prevention. The aim of this study was to analyze the relationship between adherence to the Mediterranean diet, total cholesterol blood levels, body composition and hours per day spent in in-house or outdoor among 29,159 Italian 6-14 years-old community school children (50% boys). The KidMed questionnaire, modified to handle missing information on olive oil consumption, was used to assess the adherence to the Mediterranean diet among participants. METHODS AND RESULTS: Associations between variables were tested according to 3 classes of the Mediterranean diet adherence score using analysis of variance. Participants with high adherence to Mediterranean diet were few (1%). Overall awareness of total cholesterol blood levels was low among children (4.5%), slightly higher among parents (26.2 and 24.1% in mothers and fathers, respectively). Among Mediterranean diet adherent children, BMI was significantly (p < 0.001) smaller than among the non-Mediterranean or intermediate adherent children as were the total hours spent per day watching television or playing with videogames (p < 0.001) whereas the hours/day in sport or outdoor activities were more (p < 0.001). These results were confirmed by multiple linear regression with KidMed scored 0 to 8 as dependent variable. CONCLUSION: Although awareness of total cholesterol blood levels and adherence to the Mediterranean diet are rare among community school children, only among these a healthier lifestyle was practiced with a tendency to lower CVD risks. These results are important as the first sized experience of this type in Italy.

Hypertension induced by serotonin reuptake inhibitors: analysis of two pharmacovigilance databases.

Drug-induced hypertension was described with several pharmacological classes, especially with serotonin reuptake inhibitors (SRIs). However, this link has remained controversial: the French summary of product characteristics specify a risk of hypertension only with paroxetine and sertraline. To identify a possible class effect common to all SRIs, our study investigated the reports of hypertension associated with SRIs in two pharmacovigilance databases. Two different types of investigations were performed: (i) a comparative study in VigiBase® , which is the World Health Organization (WHO) pharmacovigilance database (PVDB), from where notifications of hypertension with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were extracted. The relationship between the suspected SRIs and the occurrence of hypertension was assessed by calculating reporting odds ratio (ROR) in a case/non-case design; (ii) a descriptive study of hypertension reports associated with SRIs in the French pharmacovigilance database (FPVDB). In VigiBase® , 14 824 notifications of SRI-induced hypertension (2.5%) were identified (mean age 54.3 years, mainly women 69.1%). Among them, 3 879 (26.2%) were associated to sertraline; 3 118 (21.0%) to fluoxetine; 2 725 (18.4%) to paroxetine; 2 570 (17.3%) to citalopram; 2 295 (15.5%) to escitalopram; and 237 (1.6%) to fluvoxamine. A significant ROR value was found with all six SRIs (ROR range from 1.16 to 1.92). In the FPVDB, 24 reports of hypertension were found with all six SRIs used at standard doses, mainly in women (66.7%) with a mean age of 57.8 years and a median time of onset of 6 days. In 10 cases (42%), patients had a history of hypertension. This study, performed in real conditions of life, shows a significant pharmacovigilance safety signal between the use of SRIs and the development or worsening of hypertension.

Office white-coat effect tail and long-term cardiovascular risks in the Gubbio residential cohort study.

OBJECTIVE: The aim was to investigate whether office white-coat effect tail (OWCET), the waning of blood pressure (BP) after its waxing during office visit, predicted long-term major fatal and nonfatal events in the Gubbio residential cohort. METHODS: There were 3572 persons (44% men, 54 ±â€Š11 years old) included. OWCET was defined as a decrease of 10 mmHg or more in SBP between the third and first measurement out of a series obtained a few min apart in which the second and third were considered actual baseline SBP at enrollment. Cardiovascular (CVD), including strokes and coronary heart disease (CHD) hard criteria incidences and deaths along with all-cause deaths were considered. RESULTS: Over 185 months median follow-up, individuals with OWCET had significantly higher risk factors except for smoking, which was less frequent. OWCET was associated with an increased risk of both CVD [HR 1.25 (95% CI 1.02-1.52)] and CHD [HR 1.35 (95% CI 1.01-1.80)] events independently of traditional risk factors (age, sex, total cholesterol, HDL, cigarettes and BMI) including SBP. When effective antihypertensive treatment was considered, there was a significant higher CVD risk in individuals with OWCET (P < 0.037). In uncontrolled or untreated individuals, those with OWCET also had a higher risk (P < 0.073). CONCLUSION: In primary care, OWCET should be searched for as it can improve stratification of long-term CVD-CHD risks.

The decomposition of deformation: New metrics to enhance shape analysis in medical imaging.

In landmarks-based Shape Analysis size is measured, in most cases, with Centroid Size. Changes in shape are decomposed in affine and non affine components. Furthermore the non affine component can be in turn decomposed in a series of local deformations (partial warps). If the extent of deformation between two shapes is small, the difference between Centroid Size and m-Volume increment is barely appreciable. In medical imaging applied to soft tissues bodies can undergo very large deformations, involving large changes in size. The cardiac example, analyzed in the present paper, shows changes in m-Volume that can reach the 60%. We show here that standard Geometric Morphometrics tools (landmarks, Thin Plate Spline, and related decomposition of the deformation) can be generalized to better describe the very large deformations of biological tissues, without losing a synthetic description. In particular, the classical decomposition of the space tangent to the shape space in affine and non affine components is enriched to include also the change in size, in order to give a complete description of the tangent space to the size-and-shape space. The proposed generalization is formulated by means of a new Riemannian metric describing the change in size as change in m-Volume rather than change in Centroid Size. This leads to a redefinition of some aspects of the Kendall's size-and-shape space without losing Kendall's original formulation. This new formulation is discussed by means of simulated examples using 2D and 3D platonic shapes as well as a real example from clinical 3D echocardiographic data. We demonstrate that our decomposition based approaches discriminate very effectively healthy subjects from patients affected by Hypertrophic Cardiomyopathy.

Mediterranean diet impact on cardiovascular diseases: a narrative review.

: Cardiovascular disease (CVD) accounts for more than 17 million deaths per year worldwide. It has been estimated that the influence of lifestyle on CVD mortality amounts to 13.7% for smoking, 13.2% for poor diet, and 12% for inactive lifestyle. These results deeply impact both the healthy status of individuals and their skills in working. The impact of CVD on productivity loss accounts for the 24% in total costs for CVD management.Mediterranean diet (MedD) can positively impact on natural history of CVD. It is characterized by a relatively high consumption of inexpensive and genuine food such as cereals, vegetables, legumes, nuts, fish, fresh fruits, and olive oil as the principal source of fat, low meat consumption and low-to-moderate consumption of milk, dairy products, and wine.Its effects on cardiovascular health are related to the significant improvements in arterial stiffness. Peripheral artery disease, coronary artery disease, and chronic heart failure are all positively influenced by the MedD. Furthermore, MedD lowers the risk of sudden cardiac death due to arrhythmias.The present narrative review aims to analyze the effects of MedD on CVD.