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.).

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

National health examination surveys; a source of critical data.

The aim of this paper is to contribute technical arguments to the debate about the importance of health examination surveys and their continued use during the post-pandemic health financing crisis, and in the context of a technological innovation boom that offers new ways of collecting and analysing individual health data (e.g. artificial intelligence). Technical considerations demonstrate that health examination surveys make an irreplaceable contribution to the local availability of primary health data that can be used in a range of further studies (e.g. normative, burden-of-disease, care cascade, cost and policy impact studies) essential for informing several phases of the health planning cycle (e.g. surveillance, prioritization, resource mobilization and policy development). Examples of the use of health examination survey data in the World Health Organization (WHO) European Region (i.e. Finland, Italy, Malta and the United Kingdom of Great Britain and Northern Ireland) and the WHO Region of the Americas (i.e. Chile, Mexico, Peru and the United States of America) are presented, and reasons why health provider-led data cannot replace health examination survey data are discussed (e.g. underestimation of morbidity and susceptibility to bias). In addition, the importance of having nationally representative random samples of the general population is highlighted and we argue that health examination surveys make a critical contribution to external quality control for a country's health system by increasing the transparency and accountability of health spending. Finally, we consider future technological advances that can improve survey fieldwork and suggest ways of ensuring health examination surveys are sustainable in low-resource settings.

Cet article a pour objet d'apporter des arguments techniques au débat sur l'importance des enquêtes de santé par examen et sur leur utilisation continue pendant la crise post-pandémique du financement de la santé et dans le contexte d'un essor de l'innovation technologique qui offre de nouvelles façons de collecter et d'analyser les données individuelles sur la santé (comme l'intelligence artificielle). Les considérations techniques démontrent que les enquêtes de santé par examen apportent une contribution irremplaçable à la disponibilité locale de données de santé primaires qui peuvent servir dans une série d'études complémentaires (telles que des études normatives, sur la charge de morbidité, la cascade des soins, les coûts et l'impact des politiques). Ces études sont essentielles pour renseigner plusieurs phases du cycle de planification sanitaire (par exemple: surveillance, priorisation, mobilisation de ressources et élaboration de politiques). Cet article présente des exemples d'utilisation des données d'enquêtes de santé par examen dans la Région OMS de l'Europe (Finlande, Italie, Malte et Royaume-Uni de Grande-Bretagne et d'Irlande du Nord) et dans la Région OMS des Amériques (Chili, États-Unis d'Amérique, Mexique et Pérou) et aborde les raisons pour lesquelles les données fournies par les prestataires de soins de santé ne peuvent pas remplacer les données d'enquêtes de santé par examen (par exemple la sous-estimation de la morbidité et la vulnérabilité aux biais). En outre, il soulignet l'importance de disposer d'échantillons aléatoires représentatifs de la population générale au niveau national, et nous soutenons que les enquêtes de santé par examen apportent une contribution essentielle au contrôle externe de la qualité du système de santé d'un pays en renforçant la transparence des dépenses de santé et l'obligation de rendre des comptes à leur sujet. Enfin, nous envisageons les futures avancées technologiques susceptibles d'améliorer le travail d'enquête sur le terrain et suggérons des moyens d'assurer la viabilité des enquêtes de santé par examen dans les environnements à faibles ressources.

El objetivo de este artículo es aportar argumentos técnicos al debate sobre la importancia de las encuestas de salud y su uso continuado durante la crisis de financiación sanitaria pospandémica y en el contexto de un auge de la innovación tecnológica que ofrece nuevas formas de recopilar y analizar datos sanitarios individuales (por ejemplo, la inteligencia artificial). Las consideraciones técnicas demuestran que las encuestas de salud contribuyen de manera insustituible a la disponibilidad local de datos sanitarios primarios que pueden utilizarse en toda una serie de estudios posteriores (por ejemplo, estudios normativos, de carga de morbilidad, de cascada asistencial, de costes y de impacto de las políticas) esenciales para fundamentar varias fases del ciclo de planificación sanitaria (por ejemplo, vigilancia, establecimiento de prioridades, movilización de recursos y elaboración de políticas). Se presentan ejemplos del uso de los datos de las encuestas de salud en la Región Europea de la Organización Mundial de la Salud (Finlandia, Italia, Malta y el Reino Unido de Gran Bretaña e Irlanda del Norte) y en la Región de las Américas de la OMS (Chile, Estados Unidos de América, México y Perú) y se analizan las razones por las que los datos obtenidos por los proveedores sanitarios no pueden sustituir a los de las encuestas de salud (por ejemplo, la subestimación de la morbilidad y la posibilidad de sesgo). Además, se destaca la importancia de contar con muestras aleatorias representativas de la población general a escala nacional y se argumenta que las encuestas de salud contribuyen de forma decisiva al control de calidad externo del sistema sanitario de un país, al aumentar la transparencia y la rendición de cuentas del gasto sanitario. Por último, se examinan los futuros avances tecnológicos que pueden mejorar el trabajo de campo de las encuestas y se sugieren métodos para garantizar que las encuestas de salud sean sostenibles en entornos con pocos recursos.

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium.

Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25(OH)D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in six European countries using harmonised immunoassay data from 81 084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48·9 %; median age 50·8 years; examination period 1984-2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65·6-63·8°N), Germany (at 48·4°N), Finland (at 65·0-60·2°N), Italy (at 45·6-41·5°N), Scotland (at 58·2-55·1°N) and Spain (at 41·5°N). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as a comparator, the median 25(OH)D concentration was 3·03, 3·28, 5·41, 6·54 and 9·28 ng/ml lower in the German, Finnish, Italian, Scottish and Spanish cohort, respectively (P-value < 0·001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.

Trend in potassium intake and Na/K ratio in the Italian adult population between the 2008 and 2018 CUORE project surveys.

BACKGROUND AND AIMS: Low potassium intake, in addition to high sodium, has been associated with higher risk of hypertension and CVD. The Study assessed habitual potassium intake and sodium/potassium ratio of the Italian adult population from 2008 to 2012 to 2018-2019 based on 24-h urine collection, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU' SALUTE national surveys. METHODS AND RESULTS: Data were from cross-sectional surveys of randomly selected age-and-sex stratified samples of resident persons aged 35-74 years in 10 (out of 20) Italian regions. Urinary electrolyte and creatinine measurements were performed in a central laboratory. Analyses considered 942 men and 916 women, examined in 2008-2012, and 967 men and 1010 women, examined in 2018-2019. In 2008-2012, the age-standardized mean of potassium intake (urinary potassium accounts for 70% of potassium intake) was 3147 mg (95% CI 3086-3208) in men and 2784 mg (2727-2841) in women, whereas in 2018-2019, it was 3043 mg (2968-3118) and 2561 mg (2508-2614) respectively. In 2008-2012, age-adjusted prevalence of persons with an adequate potassium intake (i.e. ≥ 3510 mg/day) was 31% (95% CI 28-34%) for men and 18% (16-21%) for women; in 2018-2019, it was 26% (23-29%) and 12% (10-14%) respectively. The sodium/potassium ratio significantly decreased both in men and women. CONCLUSIONS: The average daily potassium intake of the Italian general adult population remains lower than the WHO and EFSA recommended level. These results suggest the need of a revision to strengthen initiatives for the promotion of an adequate potassium intake at the population level.

Trend of salt intake measured by 24-h urine collection in the Italian adult population between the 2008 and 2018 CUORE project surveys.

BACKGROUND AND AIMS: The WHO Global Action Plan for the Prevention of non-communicable diseases (NCDs) recommends a 30% relative reduction in mean population salt/sodium intake. The study assessed the trend in the habitual salt intake of the Italian adult population from 2008 to 2012 to 2018-2019 based on 24-h urinary sodium excretion, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU' SALUTE national surveys. METHODS AND RESULTS: Data were from cross-sectional surveys of randomly selected age and sex-stratified samples of resident persons aged 35-74 years in 10 (out of 20) Italian Regions distributed in North, Centre and South of the Country. Urinary sodium and creatinine measurements were carried out in a central laboratory. The analyses included 942 men and 916 women examined in 2008-2012, and 967 men and 1010 women examined in 2018-2019. The age-standardized mean daily population salt (sodium chloride) intake was 10.8 g (95% CI 10.5-11.1) in men and 8.3 g (8.1-8.5) in women in 2008-2012 and respectively 9.5 g (9.3-9.8) and 7.2 g (7.0-7.4) in 2018-2019. A statistically significant (p<0.0001) salt intake reduction was thus observed over 10 years for both genders, and all age, body mass index (BMI) and educational classes. CONCLUSIONS: The average daily salt intake of the Italian general adult population remains higher than the WHO recommended level, but a significant reduction of 12% in men and 13% in women has occurred in the past ten years. These results encourage the initiatives undertaken by the Italian Ministry of Health aimed at the reduction of salt intake at the population level.

Cardiac Troponin I and Incident Stroke in European Cohorts: Insights From the BiomarCaRE Project.

BACKGROUND AND PURPOSE: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce. METHODS: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries. RESULTS: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021). CONCLUSIONS: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.

Clinical characteristics of individuals with Down syndrome deceased with CoVID-19 in Italy-A case series.

BACKGROUND: Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19. METHODS: We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample. RESULTS: Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129). CONCLUSIONS: Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed.

Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

AIMS: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

[The Health Examination Survey at regional level: the Emilia-Romagna Region (Northern Italy) example]. / Health examination survey a livello regionale: l'esempio dell'Emilia-Romagna.

OBJECTIVES: to assess time trend of lifestyles, cardiovascular risk factors, and prevalence of high-risk conditions in random samples of the general adult population residing in Emilia-Romagna, examined in two cross-sectional surveys conducted within the Epidemiological Cardiovascular Observatory (OEC 1998-2002) and the Epidemiological Cardiovascular Observatory/Health Examination Survey (OEC/HES 2008-2012). DESIGN: cross-sectional surveys conducted on random samples of general adult population stratified by gender and age group in some municipalities of Emilia-Romagna. SETTINGS AND PARTICIPANTS: in Emilia-Romagna, 341 males and 354 females were examined in 1998-2002 and 307 males and 300 females were examined in 2008-2012. MAIN OUTCOME MEASURES: cardiovascular risk factors, high risk conditions, and proportion of population following healthy lifestyles recommendations. RESULTS: in the second survey, prevalence of hypercholesterolemia and mean values of total and LDL cholesterol were higher. Less than 30% of the sample consumes adequate quantities of vegetables and fish; cheeses, sausages, and sweets are overconsumed, as a higher cholesterol intake. CONCLUSIONS: increased in total and LDL cholesterol are partly due to the reach diet, as suggested by nutrient consumption. Appropriate preventive actions for the improvement of the lifestyles and lipid profile in the general population are recommended.

Health inequalities: a Research Positioning Exercise at the National Institute of Health, Italy.

BACKGROUND: The Italian National Institute of Health (Istituto Superiore di Sanità, ISS) considers health inequalities (HI) an important area of activity. As the scientific and technical body of the Ministry of Health and the National Health Service, ISS may play a key role to reduce HI. In order to enable ISS in addressing the new and crucial HI challenge, a Research Positioning Exercise was designed and implemented. METHODS: The Exercise included: (i) workshop to strengthen the institutional interest in the field of HI; (ii) review and analysis of ISS publications (years 2000-2017) to identify HI research topics; (iii) survey among ISS researchers regarding main research challenges to address HI in the coming years; and (iv) analysis of input on research challenges from HI international experts. RESULTS: The results of this Exercise suggest that the following points should be included in the future ISS agenda planning: (i) themes which ISS should continue working on (e.g. migrants/vulnerable groups); (ii) themes to be improved: (a) relationship between social determinants and mechanism of HI generation and (b) relationship between risk factors exposure and social determinants; and (iii) new themes to be addressed: (a) mechanisms underlying the resilience observed in Italy; (b) new socioeconomic indicators for HI monitoring; and (c) evidence-based policies aimed at reducing HI. CONCLUSION: Findings of this Exercise show that ISS researchers identified relevant areas, addressing inequalities in addressing the health. Because of ISS structural peculiarity that includes multidisciplinary expertise, the ISS could provide a significant contribution to HI research challenges and knowledge gaps.

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.

Prevalence and cardiovascular risk profile of chronic kidney disease in Italy: results of the 2008-12 National Health Examination Survey.

BACKGROUND: National surveys in countries outside Europe have reported a high prevalence (11-13%) of chronic kidney disease (CKD). Studies in Europe have provided a variable prevalence likely due to differences in study design, including age and extent of geographic areas, equation used to evaluate estimated glomerular filtration rate (eGFR) and CKD stages examined. METHODS: The 2008-12 National Health Examination Survey in Italy randomly extracted samples from the general population aged 35-79 years, stratified by age and gender, from the resident list of each Italian region (440 persons/1.5 million of residents). We estimated the prevalence of CKD by means of urinary albumin : creatinine ratio and eGFR (CKD-EPI equation-enzymatic assay of serum creatinine). Cardiovascular (CV) risk profile was also evaluated. RESULTS: Three thousand eight hundred and forty-eight men and 3704 women were examined. In the whole population, mean age was 57 ± 12 and 56 ± 12 years in men and women, respectively; hypertension was prevalent in men and women, respectively (56 and 43%) and the same held true for overweight (48 and 33%), obesity (26 and 27%), diabetes (14 and 9%) and smoking (21 and 18%), whereas CV disease was less frequent (9 and 6%). Overall, the prevalence of CKD (95% confidence interval) was 7.05% (6.48-7.65). Early stages constituted 59% of the CKD population [Stage G1-2 A2-3: 4.16% (3.71-4.61) and Stage G3-5: 2.89% (2.51-3.26)]. At multivariate regression analysis, age, obesity, hypertension, diabetes, CV disease and smoking were all independent correlates of CKD. CONCLUSIONS: CKD has a relatively lower prevalence in Italy, in particular for advanced stages, when compared with similar national surveys outside Europe. This occurs despite older age and unfavourable CV risk profile of the whole population.

Association of lifestyle and cardiovascular risk factors with lung function in a sample of the adult Italian population: a cross-sectional survey.

BACKGROUND: Some epidemiological studies have identified high values of pulmonary functions as an indicator of good health. At present little is known about the distribution of these characteristics in the general adult population. OBJECTIVE: The aim of this study is to describe pulmonary function in the Italian general population and to evaluate its association with some lifestyle and cardiovascular risk conditions using data of the OEC/HES (Cardiovascular Epidemiology Observatory/Health Examination Survey) Project, a cross-sectional survey based on the examination of random samples of the general population. METHODS: A total of 9,108 men and women aged 35-79 years were examined between 2008 and 2012. Pulmonary function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured with a spirometer and anthropometric measurements and blood pressure were also recorded, whereas lifestyle (physical activity, smoking habits), health status and drug treatment were assessed by a questionnaire. FEV1 and FVC % predicted were also calculated. Univariate analysis and a multiple linear regression were performed in order to assess associations. RESULTS: FVC and FEV1 percent predicted values were 98.0 (95% CI 97.4-98.6) and 107.3 (95% CI 106.6-107.9) for men and 108.7 (95% CI 107.9-109.4) and 113.3 (95% CI 112.6-114.1) for women. A lower mean FEV1 and FVC % predicted value was found in smokers, individuals physically inactive during their leisure time, diabetics, obese individuals and hypertensive patients. Multivariate linear regression models confirmed the independent association between risk factors and FEV1 and FVC levels. CONCLUSION: Our data confirm the inverse relationship existing between pulmonary function and cardiovascular risk factors, obesity, dyslipidemias and hypertension, all of which are conditions related to chronic diseases. An early public healthcare intervention on lifestyle could be useful to reduce the decline in pulmonary function.

Nutrition, Physical Activity and Smoking Habit in the Italian General Adult Population: CUORE Project Health Examination Survey 2018-2019.

BACKGROUND: Tobacco consumption, incorrect nutrition and insufficient physical activity/sedentariness represent modifiable NCDs risk factors in Western countries. To evaluate recent lifestyle indicators in Italy, data from the national Health Examination Survey (HES), implemented in 2018-2019 within the CUORE Project, were assessed. METHODS: Age-sex standardized results from random samples of Italian general population (35-74 years) were reported by sex, age-class, educational level and geographical area. From 2106 participants, 2090 were considered for smoking habit, 2016 for physical activity and 1578 for nutrition. Standardized questionnaires were used for smoking habit and physical activity, and the EPIC questionnaire for nutrition. RESULTS: Total cigarette current smokers were 23% in men and 19% in women; sedentariness during leisure time was 34% in men and 45% in women and at work 45% and 47% in men and women, respectively. Prevalence of balanced eating behaviours for vegetables was 28% in men and 39% in women; and for fruits 50% and 52%, respectively; prevalence of correct lifestyle (not smoker, regular physical activity and following at least five correct eating behaviours) was 7% and 12% for men and women, respectively. CONCLUSIONS: In 2018-2019, levels of unhealthy lifestyles were found to be still epidemic and basically stable compared to 10 years earlier (slight smoking habit decrease, slight sedentariness increase and slight nutrition improvements); intersectoral strategies and monitoring need to be continued.

Cost-effectiveness of applying high-sensitivity troponin I to a score for cardiovascular risk prediction in asymptomatic population.

INTRODUCTION: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness. METHODS: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses. RESULTS: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20-26) additional event-free years and 7 (95%CI: 5-9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3-13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive. CONCLUSION: Adding a person's hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups.

Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease.

BACKGROUND: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. OBJECTIVES: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. METHODS: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). RESULTS: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). CONCLUSIONS: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.

Regional and temporal differences in the associations between cardiovascular disease and its classic risk factors: an analysis of 49 cohorts from 11 European countries.

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS AND RESULTS: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

All classic cardiovascular disease (CVD) risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.