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Aims: We assess the external validation, on a "new" set of subjects, of the CAMUNI 20-year risk score, developed in a northern Italian population. Although an external validation analysis is recommended before adopting a score in clinical practice, it is rarely performed in long-term prediction equations as it requires similar long-term follow-up procedures in different cohort studies. Methods: The CAMUNI risk score was developed to estimate the 20-year risk of first coronary or ischemic stroke event, fatal or non-fatal, in 5247 (2574 men) 35- 69 subjects free of CVD at baseline enrolled in late 1980s-early 1990s in Brianza, northern Italy (derivation set). The score is based on two gender-specific Cox models, including age, total- and HDL-cholesterol, systolic blood pressure, antihypertensive treatment, cigarette smoking and diabetes. As validation set, we considered 5307 (2418 men) subjects enrolled in the Rome area in the same time span (MATISS Study). Both the derivation and the validation cohorts shared the same procedures for baseline risk assessment and follow-up procedures, including MONICA definition of acute events. We evaluated the performance of the CAMUNI score in the validation set; the Framingham CVD risk score was used for comparison. The absolute predicted risk from both scores was re-calibrated to the 20-year risk observed in the validation set. We report the calibration slope as a measure of calibration; a value different from 1 is suggestive of a different strength in predictor effects. The Area Under the ROC-curve (AUC) measured the discrimination ability; the AUC in the validation set was compared to the value in the derivation set, corrected for over-optimism. Results: The 20-year Kaplan-Meier risk of event was 16.1% (derivation set; 315 events) and 13.2% (validation set; 238 events) in men, and 6.1% (123 events) and 5.6% (119 events) in women. The calibration slope for the CAMUNI score did not significantly differ from 1 in men (1.1; 95% confidence interval 0.9; 1.2) nor in women (1.0; 0.8;1.2). The Framingham score performed equally well in men (1.1; 0.9; 1.2) but worse in women (1.3; 1.1;1.6). In the derivation set, the overoptimism corrected AUC for the CAMUNI model was 0.737 (men) and 0.801 (women); the corresponding figures in the validation set were 0.732 (95% CI: 0.727-0.738) in men, and 0.801 (0.794-0.808) in women. The Framingham score performed less well in men (0.722; 0.717-0.727) and in women (0.705; 0.699- 0.711). Conclusions: Based on these preliminary results, the CAMUNI 20-year risk score seems to be appropriate for long-term risk prediction in Italy and, more generally, in low-incidence populations. [ABSTRACT FROM AUTHOR]

Background: The number of elderly persons with cardiovascular disease (CVD) is rapidly increasing, mainly due to worldwide aging population. All CVD risk scores consider age as risk factor but most of them assume that the etiological role of other established risk factors is similar at all ages. This analyses aimed to assess the predictive role of cardiovascular risk factors in elderly persons. Methods: We considered 10,979 men and 16,533 women aged 35-74 years from cohorts in North, Centre and South of Italy with 10 years median follow-up time for fatal and non fatal coronary and cerebrovascular events (819 in men and 467 in women) validated according to MONICA criteria. In all cohorts risk factors were assessed by using standardized procedures. Two age groups were defined: adult 35-54 years of age (6,353 men and 10,358 women) and elderly 55-74 years (4,626 men and 6,175 men). Cox models were implemented including age, systolic blood pressure (SBP), total (TC) and HDL cholesterol (HDL-C), smoking, diabetes (DM - fasting blood glucose >=126 mg/dl or under glucose treatment) and hypertension treatment (HT). For continuous variables, hazard ratios (HR) were reported at 1 standard deviation higher level and for dichotomized variables, yes vs no. Results: For adult men SBP resulted having a stronger impact on CVD risk than for elderly even if not statistically significant: adult HR 1.32, 95% confidence interval 1.18-1.48, vs elderly HR 1.25, 1.15-1.36; similar results for TC (HR 1.47 vs 1.25), smoking (HR 1.91, vs 1.52), DM (HR 1.76 vs 1.56), HT (HR 2.30 vs 1.25). HDL-C resulted not significantly associated with CVD risk in elderly men. Among adult women a stronger impact was found than in elderly for SBP (HR 1.59 vs 1.26), HDLC (0.65 vs 0.84), smoking (2.43 vs 1.99), and HT (2.34 vs 1.45); the opposite for TC (1.19 vs 1.27). DM resulted not significantly associated with CVD risk in adult women. Age resulted having a stronger impact in elderly persons both in men and women (HR 1.22, 1.07-1.39, vs 1.44, 1.29-1.61; 1.45, 1.17-1.80, vs 1.63, 1.42- 1.86 respectively). Conclusions: SBP and HT resulted having a pronounced lower impact on CVD risk in elderly than in adult as well as HDL-C for men; age shows a stronger impact in elderly than in adult. Further analyses are recommended to study the reliability of risk scores based on age-specific risk models, evaluating the introduction of different risk factors and considering survival probability derived from data in elderly population. [ABSTRACT FROM AUTHOR]

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.