Alessandro Menotti

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project

AIMS The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. METHODS AND RESULTS The project assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 20,5178 persons (88,080 women and 11,7098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total cholesterol/HDL cholesterol ratio. The risk estimations are displayed graphically in simple risk charts. Predictive value of the risk charts was examined by applying them to persons aged 45-64; areas under ROC curves ranged from 0.71 to 0.84. CONCLUSIONS The SCORE risk estimation system offers direct estimation of total fatal cardiovascular risk in a format suited to the constraints of clinical practice.

The Relation between Blood Pressure and Mortality Due to Coronary Heart Disease among Men in Different Parts of the World

Background Elevated blood pressure is known to be a risk factor for death from coronary heart disease (CHD). However, it is unclear whether the risk of death from CHD in relation to blood pressure varies among populations. Methods In six populations in different parts of the world, we examined systolic and diastolic blood pressures and hypertension in relation to long-term mortality from CHD, both with and without adjustment for variability in blood pressure within individual subjects. Blood pressure was measured at base line in 12,031 men (age range, 40 to 59 years) who were free of CHD. During 25 years of follow-up, 1291 men died from CHD. Results At systolic and diastolic blood pressures of about 140 and 85 mm Hg, respectively, 25-year rates of mortality from CHD (standardized for age) varied by a factor of more than three among the populations. Rates in the United States and northern Europe were high (approximately 70 deaths per 10,000 person-years), but rates in Japan and Mediterranean southern Europ...

Vascular Factors and Risk of Dementia: Design of the Three-City Study and Baseline Characteristics of the Study Population

Objective: To describe the baseline characteristics of the participants in the Three-City (3C) Study, a study aiming to evaluate the risk of dementia and cognitive impairment attributable to vascular factors. Methods: Between 1999 and 2001, 9,693 persons aged 65 years and over, noninstitutionalized, were recruited from the electoral rolls of three French cities, i.e. Bordeaux, Dijon and Montpellier. Health-related data were collected during face-to-face interviews using standardized questionnaires. The baseline examination included cognitive testing and diagnosis of dementia, and assessment of vascular risk factors, including blood pressure measurements, ultrasound examination of the carotid arteries, and measurement of biological parameters (glycemia, total, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinemia); 3,442 magnetic resonance imaging (MRI) examinations were performed in subjects aged 65–79. Measurements of ultrasound, blood, and MRI parameters were centralized. Two follow-up examinations (at 2 and 4 years) were planned. Results: After exclusion of the participants who had subsequently refused the medical interview, the 3C Study sample consisted of 3,649 men (39.3%) and 5,645 women, mean age 74.4 years, with a relatively high level of education and income. Forty-two percent of the participants reported to be followed up for hypertension, about one third for hypercholesterolemia, and 8% for diabetes; 65% had elevated blood pressure measures (systolic blood pressure ≧140 or diastolic blood pressure ≧90). The proportion of Mini-Mental State Examination scores below 24 was 7% and dementia was diagnosed in 2.2% of the participants. Conclusion: Distribution of baseline characteristics of the 3C Study participants suggests that this study will provide a unique opportunity to estimate the risk of dementia attributable to vascular factors.

Coronary heart disease: overweight and obesity as risk factors.

Abstract The relationship of relative weight and of skinfold thickness to the 5-year incidence (632 cases) of coronary heart disease was examined in men aged 40 through 59 years at entry to the stu...

Prevalence of morbidity and multimorbidity in elderly male populations and their impact on 10-year all-cause mortality: The FINE study (Finland, Italy, Netherlands, Elderly).

Older males are known to carry, more likely than younger people, one or more chronic diseases with an expected impact on mortality. This study was aimed at identifying the relationship of prevalent chronic diseases in elderly populations of different countries with all-cause mortality. Men aged 65-84 from defined areas were enrolled in Finland (N=716), the Netherlands (N=887) and Italy (N=682). They were survivors of cohorts studied for 25 years within the Seven Countries Study. Major chronic diseases were diagnosed at entry. Ten-year follow-up for mortality was completed. Entry prevalence of selected chronic diseases was higher in Finland (56%) than in Italy (51%) and the Netherlands (44%). Ten-year age-adjusted death rates from all causes were higher in Finland (565 per 1000) and lower in the Netherlands (478 per 1000) and Italy (445 per 1000). The absolute risk of death related to chronic disease was high in the three countries, but was higher in Finland than in the Netherlands and Italy. The most lethal condition was stroke, with 10-year death rates of 806 per 1000 in Finland and 707 and 729 per 1000 in the Netherlands and Italy, respectively. The relative risk of all-cause mortality for a set of seven chronic diseases (coronary heart disease, heart failure, claudicatio intermittens, cerebrovascular accidents, diabetes, COPD and cancer) adjusted by age, other diseases and cohort was less than two for each condition, except cerebrovascular accidents in the Netherlands (RR 2.20). In general, relative risk was higher in Finland, intermediate in the Netherlands and lower in Italy, where only cerebrovascular accidents, intermittent claudication, diabetes and the presence of any chronic condition had a significant relative risk. About one third of men had one chronic disease, and between 10% and 15% had two diseases. The coexistence of any two or three chronic conditions was associated with a relative risk of 2 or more in Finland and the Netherlands and less than 2 in Italy. In these elderly men prevalent morbidity and comorbidity was relatively common and it explained a large proportion of excess in all-cause mortality in 10 years of follow-up.

HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk

OBJECTIVE We aimed to clarify some previous inconsistencies regarding the role of high density lipoprotein cholesterol (HDL-C) as a CVD protective factor. METHODS The SCORE dataset contained data on HDL-C for 104,961 individuals (45% women) without pre-existing coronary heart disease (CHD). These were from 7 pooled European prospective studies. The effect of HDL-C, both in quintiles and as a continuous variable, on risk of CVD and CHD mortality was examined, using Cox proportional hazards model, adjusted for age, total cholesterol, systolic blood pressure, smoking, diabetes and body mass index and stratified by gender, age group, country and category of SCORE CVD risk. RESULTS A strong, graded, independent, inverse relationship between HDL-C and both CVD and CHD mortality was demonstrated. Adjusted hazard ratios per 0.5mmol/l increase in HDL-C were 0.60 (0.51, 0.69) and 0.76 (0.70, 0.83) in women and men, respectively for the CVD mortality endpoint. The corresponding hazard ratios were 0.53 (0.42, 0.68) and 0.79 (0.64, 0.98) in elderly women and men, respectively. The relationship was significant in all SCORE CVD risk strata and age groups. CONCLUSIONS This multivariable analysis, the largest of its kind to date, has confirmed the inverse, independent, strong and graded relationship between HDL-C and both CVD and CHD mortality. We have clarified previous suggestions that the relationship is stronger in women and that it applies in all age groups. This is the first prospective study to demonstrate the independent relationship specifically in healthy elderly women and to show that the relationship holds at all levels of total CVD risk.

Blood pressure control in Italy: Results of recent surveys on hypertension

Background Blood pressure (BP) control is reported to be poor in hypertensive patients worldwide. Objective BP levels, the rate of BP control, prevalence of risk factors and total cardiovascular risk were assessed in a large cohort of hypertensive patients, derived from recent surveys performed in Italy. Methods Fifteen studies on hypertension, performed in different clinical settings (general population, general clinical practice, specialist outpatient clinics and hypertension centres) over the past decade were considered. Results The overall sample included 52 715 hypertensive patients (26 315 men and 26 410 women, mean age 57.3 ± 6.9 years). Despite the high percentage of patients on stable antihypertensive treatment (n = 36 556, 69%), mean systolic and diastolic BP levels were 147.8 ± 8.5 and 89.5 ± 5.2 mmHg, respectively. On the basis of the nature of the study (population surveys or clinical referrals), systolic BP levels were consistently higher than the normality threshold in both settings (142.6 ± 12.4/84.8 ± 3.7 mmHg and 150.4 ± 4.6/91.9 ± 4.1 mmHg, respectively). The BP stratification could be assessed in 40 829 individuals: 4.5% had optimal, 9.2% normal and 8.3% high-normal BP levels, however, the large majority were in grade 1 (39%) or grades 2–3 (32.6%) hypertension. In the overall sample, 55.9% of hypertensive patients had hypercholesterolemia, 28.7% were smokers, 36.4% were overweight or obese and 15.0% had diabetes mellitus. Cardiovascular risk stratification was assessed in 37 813 hypertensives: 23.2% had low, 33.9% moderate, 30.2% high and 12.7% very high added risk. Conclusion Our analysis demonstrates the persistence of poor BP control and high prevalence of risk factors, supporting the need for more effective, comprehensive and urgent actions to improve the clinical management of hypertension.

Dietary factors and pulmonary function: a cross sectional study in middle aged men from three European countries

BACKGROUND Results of epidemiological studies relating individual dietary factors to chronic obstructive pulmonary disease (COPD) are inconsistent. To evaluate the cross sectional association of dietary factors with pulmonary function, data were collected from middle aged men in three European countries. METHODS The data were collected in the 1960s in Finland (n = 1248), Italy (n = 1386), and the Netherlands (n = 691). Dietary intake was estimated using the cross-check dietary history method. Forced expiratory volume (FEV0.75 or FEV1, here called FEV) was measured by spirometry. Associations were adjusted for age, height, smoking, body mass index (BMI), alcohol consumption, and energy intake. RESULTS FEV was positively associated with intake of vitamin E in Finland, with intake of fruit in Italy, and with intake of β-carotene in the Netherlands. In all three countries men with intakes of both fruit and vegetables above the median had a higher FEV than those with a low intake of both foods. The difference in FEV ranged from 110 to 169 ml before and from 53 to 118 ml after energy adjustment. Differences in FEV for intake of three antioxidants (vitamins C and E and β-carotene) above versus below the median ranged from 61 to 181 ml before and from –35 to 58 ml after energy adjustment. Intake of fish was not associated with FEV. CONCLUSIONS In three European countries a high intake of fruit and vegetables was positively associated with pulmonary function. A high intake of all three antioxidants tended to be positively associated with pulmonary function before, but not after, adjustment for energy intake. Associations of individual antioxidants with pulmonary function were not consistent across countries.

Treatment of Isolated Systolic Hypertension: The SHELL Study Results

Objective: Our aim was to compare the effect of lacidipine and chlorthalidone on cardiovascular outcome as a primary parameter and blood pressure as a secondary in elderly patients with isolated systolic hypertension in a prospective study with an open design. Methods: 1882 males and females outpatients ≥60 years were randomly assigned to the administration of chlorthalidone 12.5 mg o.d. or lacidipine 4 mg o.d. Patients were recruited if sitting systolic blood pressure was ≥160 mmHg with a diastolic blood pressure equal or lower than 95 mmHg. Primary endpoint was a composite of cardiovascular and cerebrovascular events. Results: At randomization mean systolic blood pressure was 178.1 mmHg in the lacidipine and 178.2 mmHg in the chlorthalidone group, the corresponding mean diastolic values being 86.9 and 86.8 mmHg. In both lacidipine and chlorthalidone groups treatment caused a significant (p < 0.001) and marked systolic blood pressure reduction which was maintained throughout the treatment period with a significant (p < 0.001) and steady although less marked reduction in diastolic blood pressure as well. At the end of treatment period (median 32 months), the reduction was 36.8/8.1 mmHg (systolic/diastolic) in the chlorthalidone and 38.4/7.9 mmHg in the lacidipine group, the final on treatment blood pressures being 142.0/79.2 and 143.2/79.5 mmHg, respectively. Treatments were similarly effective in males and females and in age groups between 60 and 69 years (n = 763), 70 and 79 years (n = 744) and ≥80 years (n = 375). Similar reductions were obtained in a subgroup of patients (n = 209) followed in double-blind fashion for 1 year. The overall incidence of the primary endpoints was 9.3% with no significant between-group difference. Total mortality was also similar between groups. Conclusions: In elderly patients with isolated systolic hypertension, administration of lacidipine or chlorthalidone markedly reduced systolic blood pressure with no difference in the incidence of cardiovascular events and total mortality.

How much does HDL cholesterol add to risk estimation? A report from the SCORE investigators

Background Systematic COronary Risk Evaluation (SCORE), the risk estimation system recommended by the European guidelines on cardiovascular disease prevention, estimates 10-year risk of cardiovascular disease mortality based on age, sex, country of origin, systolic blood pressure, smoking status and either total cholesterol (TC) or TC/high-density lipoprotein cholesterol (HDL-C) ratio. As, counterintuitively, these two systems perform very similarly, we have investigated whether incorporating HDL-C and TC as separate variables improves risk estimation. Methods The study consisted of 57 302 men and 47 659 women. Cox proportional hazards method was used to derive the function including HDL-C and an identical function without HDL-C for comparison. Risk charts were developed to illustrate the results. Results Inclusion of HDL-C resulted in a modest but statistically significant improvement in risk estimation, based on the area under receiver operating characteristic curve (AUROC); 0.814 versus 0.808, P value less than 0.0001, for the functions with and without HDL-C, respectively. Addition of HDL-C also resulted in a significant and important improvement in risk estimation as measured by net reclassification index, which is highly clinically relevant. Improvement in risk estimation was greatest in women from high-risk countries, in terms of both AUROC and net reclassification index. Conclusion For the general population, the inclusion of HDL-C in risk estimation results in only a modest improvement in overall risk estimation based on AUROC. However, when using the more clinically that examines reclassification of individuals, clinically useful improvements occur. Inclusion of HDL may be particularly useful in women from high-risk countries and individuals with unusually high or low HDL-C levels. Addition of HDL-C is particularly applicable to electronic, interactive risk estimation systems such as HeartScore.