Chiara Donfrancesco

Background/Objectives: Nutrition during the reproductive years shapes women’s immediate health, fertility, pregnancy outcomes, and long-term offspring well-being. This position paper narratively synthesizes and critically appraises evidence on how dietary patterns, macro-/micronutrients, and supplementation influence women’s health, female fertility, and reproductive outcomes, to inform practical recommendations. Methods: We narratively reviewed recent reviews, cohort studies, clinical trials, and public-health guidance on macronutrients, key micronutrients, dietary patterns (with emphasis on the Mediterranean diet), ultra-processed food (UPF) intake, and targeted supplementation relevant to menstrual, metabolic, cardiovascular, skeletal, and reproductive outcomes. Results: Balanced, diverse diets rich in whole and minimally processed foods support hormonal regulation, ovulatory function, healthy gestation, and chronic-disease risk reduction. Priority nutrients include iron, folate, calcium, vitamin D, zinc, vitamin B12, and long-chain omega-3s (DHA), with supplementation considered when dietary intake or bioavailability is inadequate. Evidence consistently links Mediterranean-style eating to improved metabolic health, insulin sensitivity, IVF success, lower gestational diabetes risk, and favorable neonatal outcomes. High UPF consumption is associated with poorer diet quality, inflammation, adverse pregnancy outcomes, and potential reproductive impairment, warranting a reduction in favor of nutrient-dense foods. Diet also influences cardiovascular and bone health through effects on lipids, glycemia, blood pressure, and mineral/vitamin status, with fiber-rich carbohydrates, unsaturated fats (notably olive oil), and adequate calcium–vitamin D emerging as central levers. Conclusions: For women of childbearing age, a Mediterranean-aligned, minimally processed dietary pattern—tailored to individual needs and complemented by prudent use of folate, iron, vitamin D, calcium, B12, and DHA when indicated—offers robust benefits across reproductive, metabolic, cardiovascular, and skeletal domains. Public-health actions should improve access to healthy foods, curb UPF marketing, and embed personalized nutrition counseling in routine care; further longitudinal research from preconception through postpartum is needed.

Aims: Deleterious effects of Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline. Methods and results: Overall 66 495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in ‘0/1 CVRF’ (low risk; n = 41 770) and ‘≥2 CVRFs’ (increased risk; n = 24 725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th vs. ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events. During a median follow-up of 9.7 years, 3467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12–1.71) vs. 1.27 (95% CI, 1.10–1.46) in those having 0/1 vs. ≥2 CVRFs at baseline (Pinteraction 0.50). Conclusion: Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.

Background: The reduction of NCDs premature mortality is pursued by the WHO; risk conditions targets are recommended as well as population-level monitoring of cardiovascular disease (CVD) risk. The Italian Ministry of Health (MoH) has strengthened prevention/health promotion and supported periodic CVD risk assessment through national health examination surveys (HESs), funded by the MoH-CCM and conducted within the CUORE Project. Methods: In 2023 a new HES started including the 10-year fatal and non-fatal CVD risk assessment based on knowledge of sex, age, smoking habit, measured systolic blood pressure and fasting total and HDL serum cholesterol, and presence of diabetes (on measured fasting serum glycemia and/or treatment) and anti-hypertensive therapy. Up to now, data from random samples of residents in 7 Regions (of 20 regions) distributed in North, Centre and South of Italy, aged 35-69 years, without previous CVD, are available (585 men, 617 women). Determinations were assayed by a central lab. CUORE Project functions developed on and for the Italian adults were used. Results: Mean values of the CVD risk assessment resulted 6.9% (95% CI: 6.3-7.4) in men and 2.3% (2.1-2.5) in women. For men aged 35-44 years risk was 1.6% (1.5-1.8), for 45-54 years 3.8% (3.5-4.2), for 55-64 years 10.0% (9.0-10.9), for 65-69 years 17.6% (16.4-18.9); for women was 0.5% (0.4-0.6), 1.0% (0.9-1.1), 3.3% (2.9-3.7) and 6.0% (5.5-6.6) respectively. Prevalence of CVD risk less than 5% was 57% (49-64) in men and 88% (84-93) in women, of 10-15% risk were 22% (15-28) of men and 9% (5-14) of women, of 15-20% risk were 5% (1.6-8.0) of men and 0% of women, of over 20% risk were 2% (0-3.6) of men and 0% of women. Conclusions: Compared to 2008, these data showed stable mean levels of CVD risk both in men and women at any age-classes and stable prevalence of CVD risk classes. CVD risk perception represents a challenge in primary prevention especially for young age groups and women. Key messages: • In the Italian general population, CVD risk assessment remained stable compared to 15 years ago. • CVD risk perception represents a challenge in primary prevention.

Background: The WHO recommends a 30% relative reduction in mean population intake of salt/sodium within 2025 (baseline 2010) and an adequate potassium intake. To these ends, the Italian Ministry of Health (MoH) has strengthened prevention/health promotion. To update the assessment of the habitual salt and potassium intake in the Italian general adult population, national health examination surveys (HESs), funded by the MoH-CCM, are conducted within the CUORE Project. Methods: In 2023 a new HES started including salt and potassium intake assessment by the use of 24h urine collection. Up to now, data from random samples of residents in 7 Regions (of 20 regions) distributed in North, Centre and South of Italy and aged 35-74 years are available (686 men, 702 women). Urinary excretion is assayed by a central lab. Persons with urinary volume < 500 ml and/or a urinary creatinine content referred to body weight outside the range of population mean ± 2 standard deviations are excluded. Results: Out of 657 men and 671 women, mean level of salt per day was 9,2 g (95% CI: 9,0-9.5 g) and 7,1 g (6,9-7,3 g) respectively, and mean level of potassium per day was 2,9 g (2,8-3,0 g) and 2,4 g (2,3-2,5 g) respectively. A salt intake level lower than the WHO recommended target of 5g/day was detected in 9,5 % (5,2 -13,9 %) of men and 23,7 % (17,5 -29,9 %) of women and a potassium intake level higher than the WHO recommended target of 3510 mg/day was detected in 22,4 % (16,3 -28,6 %) of men and 9,7 % (5,4 -14,0 %) of women. Conclusions: These preliminary data showed that in Italian adults the average salt intake is still higher and the average potassium intake is still lower than recommended. Compared to 2008, the habitual salt intake decreased of about 12% in 2018 and remained stable in 2023; the habitual potassium intake remained stable in 2008, 2018 and 2023.These results justify and encourage the ongoing preventive initiatives of MoH, facilitating the meeting of WHO targets. Key messages: • In Italian adults the average salt intake is still higher than recommended and the habitual salt intake decreased compared to 15 years ago. • In Italian adults the average potassium intake is still lower than recommended and remained stable compared to 15 years ago.

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.

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. 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 (P_interaction = 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 P_interaction = 0.024). 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. C-reactive protein as a possible modifier of lipoprotein(a)-related risk for coronary heart disease in Europe. CHD, coronary heart disease; CI, confidence interval; Lp(a), lipoprotein(a); FU, follow-up; F, fifth; hsCRP, high-sensitive C-reactive protein; sHR, sub-distribution hazard ratio.

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.

National health examination surveys (HESs) have been developed to provide important information that cannot be obtained from other sources. A HES combines information obtained by asking participants questions with biophysical measurements taken by trained field staff. They are observational studies with the highest external validity and make specific contributions to both population (public health) and individual health. Few countries have a track record of a regular wide-ranging HES, but these are the basis of many reports and scientific papers. Despite this, little evidence about HES usefulness and impact or the factors that influence HES effectiveness have been disseminated. This paper presents examples of HES contributions to society in both Europe and the Americas. We sought information by emailing a wide list of people involved in running or using national HESs across Europe and the Americas. We asked for examples of where examination data from their HES had been used in national or regional policymaking. We found multiple examples of HES data being used for agenda-setting, including by highlighting nutritional needs and identifying underdiagnosis and poor management of certain conditions. We also found many ways in which HES have been used to monitor the impact of policies and define population norms. HES data have also been used in policy formation and implementation. HES data are influential and powerful. There is need for global support, financing and networking to transfer capacities and innovation in both fieldwork and laboratory technology.

Aims: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. Methods and results: We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan–Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81). Conclusion: Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.

Objectives To assess in the Italian general adult population the trends of blood pressure (BP) and prevalence of raised BP (RBP), hypertension and its control in order to evaluate population health and care, and the achievement of an RBP 25% relative reduction as recommended by the WHO at population level. Design Results comparison of health examination surveys, cross-sectional observational studies based on health examination of randomly selected age and sex stratified samples including residents aged 35–74 years. Data of the 2018/2019 survey were compared with the previous ones collected in 1998/2002 and 2008/2012. Setting Health examination surveys conducted in Italy within the CUORE Project following standardised methodologies. Participants 2985 men and 2955 women examined in 1998/2002, 2218 men and 2204 women examined in 2008/2012 and 1031 men and 1066 women examined in 2018/2019. Primary and secondary outcome measures Age-standardised mean of BP, prevalence of RBP (systolic BP and/or diastolic BP ≥140/90 mm Hg), hypertension (presenting or being treated for RBP) and its awareness and control, according to sex, age class and educational level. Results In 2018/2019, a significant reduction was observed in systolic BP and diastolic BP in men (1998/2002: 136/86 mm Hg; 2008/2012: 132/84 mm Hg; and 2018/2019: 132/78 mm Hg) and women (132/82 mm Hg, 126/78 mm Hg and 122/73 mm Hg), and in the prevalence of RBP (50%, 40% and 30% in men and 39%, 25% and 16% in women) and of hypertension (54%, 49% and 44% in men and 45%, 35% and 32% in women). Trends were consistent by age and education attainment. In 2018/2019, hypertensive men and women with controlled BP were only 27% and 41%, but a significant favourable trend was observed. Conclusions Data from 2018/2019 underlined that RBP is still commonly observed in the Italian population aged 35–74 years, however, the WHO RBP target at that time may be considered met.