The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Heritability of arterial stiffness and carotid intima-media thickness: an Italian twin study.

BACKGROUND AND AIMS: Carotid intima-media thickness (IMT) and arterial stiffness parameters, including aortic augmentation index (AIx) and pulse wave velocity (PWV), are independent predictors of stroke and cardiovascular disease. Genetic effects on these traits were never explored in a Mediterranean country. The present study aims to quantify the contribution of genes, environment and age to carotid IMT and aortic Aix and PWV. METHODS AND RESULTS: The twin design was used. A total of 348 adult twins from the Italian Twin Register underwent measurements of carotid IMT and aortic PWV and AIx in three university hospitals located in Rome, Padua and Perugia. Carotid IMT was measured by B-mode ultrasound, aortic PWV and AIx by Arteriograph. Genetic modelling was performed to decompose total variance of traits into genetic, shared and unshared environmental and age components. For each phenotype, the best-fitting model included additive genetic, unshared environmental and age effects. For IMT, heritability was 0.32 (95% confidence interval (CI): 0.25-0.38), unshared environmental component was 0.25 (0.18-0.32) and age contribution was 0.44 (0.39-0.49). For AIx and PWV, heritabilities were 0.42 (0.29-0.55) and 0.49 (0.35-0.62), unshared environmental components were 0.31 (0.22-0.44) and 0.37 (0.26-0.51) and age contributions were 0.27 (0.16-0.39) and 0.14 (0.06-0.24), respectively. CONCLUSION: This study shows substantial genetic and unshared environmental influences on carotid intima-media thickness and arterial stiffness and confirms the relevant role of age in the aetiology of these traits. Further support is provided for prevention and health promotion strategies based on modifiable factors.

Health status and 6 years survival of 552 90+ Italian sib-ships recruited within the EU Project GEHA (GEnetics of Healthy Ageing).

In a scenario of increasing life expectancy worldwide, it is mandatory to identify the characteristics of a healthy aging phenotype, including survival predictors, and to disentangle those related to environment/lifestyle versus those related to familiarity/genetics. To this aim we comprehensively characterised a cohort of 1,160 Italian subjects of 90 years and over (90+, mean age 93 years; age range 90-106 years) followed for 6 years survival, belonging to 552 sib-ships (familiar longevity) recruited (2005-2008) within the EU-funded GEHA project in three Italian geographic areas (Northern, Central and Southern Italy) different for urban/rural and socio-economical characteristics. On the whole, the following factors emerged as significant predictors of survival after 90 years of age: absence of cognitive impairment and physical disability, high hand grip strength scores and body mass index (BMI) values, "excellent/good" self-reported health, high haemoglobin and total cholesterol levels and low creatinine levels. These parameters, excluding BMI values, were also significantly associated within sib-ships, suggesting a strong familial/genetic component. Geographical micro-heterogeneity of survival predictors emerged, such as functional and physical status being more important in Southern than in Central and Northern Italy. In conclusion, we identified modifiable survival predictors related to specific domains, whose role and importance vary according to the geographic area considered and which can help in interpreting the genetic results obtained by the GEHA project, whose major aim is the comprehensive evaluation of phenotypic and genetic data.

Gender differentials in life expectancy in Italy.

OBJECTIVE: To analyze the gender differential in life expectancy in Italy from 1970 to 1997, to determine which ages and causes of death mostly influenced its trend. METHODS: Pollard method was used to explain which ages and which pathologies give the highest contribution to the gender differential. RESULTS: A slight reduction of the gender differential has been observed since 1980. The olds and very olds became the most relevant contributors to the differential. Cardiovascular diseases were the principal contributing causes of death until 1980 and Cancer replaced them afterwards. CONCLUSION: Relatively recent adoption of unhealthy life styles by women together with an opposite process run by young men towards healthier behaviour, seem to be at the basis of the slight reduction of the gender differential in life expectancy observed since 1980.

Differential impact of combined antiretroviral therapy on the survival of italian patients with specific AIDS-defining illnesses.

BACKGROUND: A decrease in HIV-related mortality and morbidity has been observed since 1996 in most developed countries as a consequence of the extensive use of combined antiretroviral therapies. The purpose of this study was to investigate whether combined antiretroviral therapies had a differential impact on the survival of patients with different AIDS-defining illnesses (ADIs). METHODS: In total, 35,318 persons representing all the adults with AIDS (PWAs) diagnosed in Italy from January 1, 1990 to August 31, 1998 were studied. Actuarial life tables and the Kaplan-Meier method were used to estimate the cumulative probability of survival; the multivariate Cox proportional hazards model was used to estimate adjusted relative hazard of death (RH). RESULTS: Among PWAs diagnosed after 1995, the proportion of survivors 24 months after diagnosis was more than doubled (66%) compared with that of PWAs diagnosed before the end of 1995 (31%). Significantly decreased RHs for some ADIs were observed as early as 1996 (i.e., esophageal candidiasis, Pneumocystis carinii pneumonia, brain toxoplasmosis, HIV-wasting syndrome, and pulmonary tuberculosis). In the last period (1997-1998), the decrease was marked and significant for almost all the ADIs, ranging from 55% to 80% compared with the RHs of the reference year (1995). Conversely, primary lymphoma of the brain and Burkitt's lymphoma showed a low and not statistically significant decrease; these were the ADIs with the worst outcome. CONCLUSIONS: After 1995, there was a rather uniform increase in the survival of PWAs diagnosed with most specific ADIs but not for patients affected by primary brain lymphoma and Burkitt's lymphoma. The determinants of this differential effect need to be investigated.

The impact of the major causes of death on life expectancy in Italy.

BACKGROUND: This study aims to evaluate the contribution of the reduction in major cardiovascular diseases (CVD), malignant neoplasms (MN), accidents and AIDS mortality to the gains in life expectancy observed during the decade 1985-1994, as well as to calculate and compare the potential gains due to the partial or total elimination of these causes. METHODS: Mortality data from the Italian Mortality Data Base were analysed by the method of decomposition of changes in life expectancy and the partial multiple decrement life table technique. RESULTS: In Italy, considering the decade 1985-1994, the gain in life expectancy at birth was 2.27 years for men and 2.16 for women. The major contribution to this increase was the reduction in CVD mortality followed by fewer deaths from accidents and MN. Conversely, AIDS caused a loss in the length of life of adults. Major potential gains in life expectancy at birth could be obtained by the elimination or even partial reduction of CVD and MN mortality. When working life (15-64 years) is considered, the relative importance of the causes changes. The elimination of accidents and AIDS would result in increased life expectancy longer than that associated with a 50% reduction in CVD. CONCLUSIONS: The findings of this study provide useful information which could contribute to a more effective allocation of resources for research activity and public health programmes.

Creutzfeldt-Jakob disease mortality in Italy, 1982-1996.

We report an estimate of Creutzfeldt-Jakob disease (CJD) deaths in Italy from 1982 to 1996 by using mortality data based on a retrospective review of deaths taken from the mortality data base of the Italian Census Bureau (ISTAT, years 1982-1993), and on the prospective surveillance performed by the Italian National Register of CJD (years 1993-1996). One hundred and ninety-five and 154 deaths attributed to CJD were recorded by ISTAT and the CJD register, respectively. The average annual age-adjusted mortality rate was 0. 45 and 0.84 deaths per million for the period 1982-1993 and 1993-1996, respectively. The yearly increase in the number of CJD deaths was mostly due to a rise in the reported deaths among people older than 60 years. The result of the linkage between ISTAT and the CJD register shows that the integrated age-adjusted mortality rate for 1993 was about 1 case per million, similar to the rates observed in other studies and obtained by the CJD register alone in 1996. This study indicates that the data of the CJD register is accurate and therefore important for assessing eventual changes in the characteristics of the disease resulting from bovine spongiform encephalopathy or other new risk factors.

Premature mortality in Italy during the first decade of the AIDS epidemic: 1984-1993.

BACKGROUND: AIDS has become a leading cause of premature mortality in many countries, owing to the decline in other major causes of premature death and the increase in AIDS itself. This study was carried out to determine the trends in premature mortality due to selected causes in Italy. METHODS: Data from the Italian Mortality Data Base, for the ten years from 1984 to 1993 (the first decade of the AIDS epidemic) were analysed. Premature mortality was measured in terms of years of potential life lost before the age of 70 years (YPLL), excluding infant mortality. Trends in premature mortality due to AIDS were compared with those of the principal causes of premature death: lung cancer, colon-rectum cancer, stomach cancer, leukaemia, female breast cancer, uterine cancer, myocardial infarction, stroke, liver diseases, suicide, road accidents and overdose. RESULTS: In this period there has been a marked increase in premature mortality from AIDS both among males aged 1-69 years (from a rate of YPLL of 0.01 per 1000 in 1984 to 3.71 in 1993) and females of the same age group (from 0 deaths in 1984 to a rate of YPLL of 1.02). Throughout the same period all the other causes of premature death have been declining, with the exception of suicide and overdose among males, and overdose and lung cancer among females. For people aged 25-44 years, AIDS has become the greatest cause of premature death. The increasing trend in premature mortality due to AIDS is most pronounced in the northern and central areas of Italy. CONCLUSIONS: AIDS is the leading cause of death among males aged 25-44 years in Italy and is having an important impact on premature mortality among females in the same age group.