Genetic associations with longevity are on average stronger in females than in males.

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that "one-size-fits-all" for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

Assessment of Excess Mortality in Italy in 2020-2021 as a Function of Selected Macro-Factors.

BACKGROUND: Excess mortality (EM) can reliably capture the impact of a pandemic, this study aims at assessing the numerous factors associated with EM during the COVID-19 pandemic in Italy. METHODS: Mortality records (ISTAT 2015-2021) aggregated in the 610 Italian Labour Market Areas (LMAs) were used to obtain the EM P-scores to associate EM with socioeconomic variables. A two-step analysis was implemented: (1) Functional representation of EM and clustering. (2) Distinct functional regression by cluster. RESULTS: The LMAs are divided into four clusters: 1 low EM; 2 moderate EM; 3 high EM; and 4 high EM-first wave. Low-Income showed a negative association with EM clusters 1 and 4. Population density and percentage of over 70 did not seem to affect EM significantly. Bed availability positively associates with EM during the first wave. The employment rate positively associates with EM during the first two waves, becoming negatively associated when the vaccination campaign began. CONCLUSIONS: The clustering shows diverse behaviours by geography and time, the impact of socioeconomic characteristics, and local governments and health services' responses. The LMAs allow to draw a clear picture of local characteristics associated with the spread of the virus. The employment rate trend confirmed that essential workers were at risk, especially during the first wave.

Frailty at death: An examination of multiple causes of death in four low mortality countries in 2017.

BACKGROUND: The increasing prevalence of frailty in aging populations represents a major social and public health challenge which warrants a better understanding of the contribution of frailty to the morbid process. OBJECTIVE: To examine frailty-related mortality as reported on the death certificate in France, Italy, Spain and the United States in 2017. METHODS: We identify frailty at death for the population aged 50 years and over in France, Italy, Spain and the United States. We estimate the proportions of deaths by sex, age group and country with specific frailty-related ICD-codes on the death certificate 1) as the underlying cause of death (UC), 2) elsewhere in Part I (sequence of diseases or conditions or events leading directly to death), and 3) anywhere in Part II (conditions that do not belong in Part I but whose presence contributed to death). RESULTS: The age-standardized proportion of deaths with frailty at ages 50 and over is highest in Italy (25.0%), then in France (24.1%) and Spain (17.3%), and lowest in the United States (14.0%). Cross-country differences are smaller when frailty-related codes are either the underlying cause of the death or reported in Part II. Frailty-related mortality increases with age and is higher among females than males. Dementia is the most frequently reported frailty-related code. CONCLUSIONS: Notable cross-country differences were found in the prevalence and the type of frailty-related symptoms at death even after adjusting for differential age distributions.

Socioeconomic inequalities in health status and survival: a cohort study in Rome.

OBJECTIVES: To analyse the association between individual and contextual socioeconomic position (SEP) with health status and to investigate the role of SEP and baseline health status on survival. DESIGN: Cross-sectional and cohort study. SETTING: Rome, Italy. PARTICIPANTS, PRIMARY AND SECONDARY OUTCOMES: We selected the 25-99 year-olds included in the Rome 2011 census cohort. As a measure of health status on the census reference date (09 October 2011), we used the presence of chronic or rare conditions from the Disease-Related Co-payment Exemption Registry, a database implemented to provide free care to people with chronic or rare diseases. We used logistic regression to analyse the association between both individual (educational attainment) and contextual SEP (neighbourhood real estate price quintiles) with baseline health status. We analysed the role of SEP and the presence of chronic or rare conditions on 5-year survival (until 31 December 2016) using accelerated failure time models with Weibull distribution, reporting time ratios (TRs; 95% CI). RESULTS: In middle-aged, subjects with low SEP (either individual or contextual) had a prevalence of chronic conditions comparable with the prevalence in high SEP individuals 10 years older. Adjusted logistic models confirmed the direct association between SEP and baseline health status in both women and men. The lowest educated were up to 67% more likely to have a chronic condition than the highest educated, while the difference was up to 86% for lowest versus highest contextual SEP. Low SEP and the presence of chronic conditions were associated with shorter survival times in both sexes, lowest versus highest educated TR was TR=0.79 for women (95% CI: 0.77 to 0.81) and TR=0.71 for men (95% CI: 0.70 to 0.73). The contextual SEP shrunk survival times by about 10%. CONCLUSION: Inequalities were present in both baseline health and survival. The association between SEP and survival was independent of baseline health status.

Mortality temporal trends and cancer incidence profiles of residents in the petrochemical industrially contaminated town of Gela (Sicily, Italy).

OBJECTIVE: In 2000, a vast area in Gela (Sicily, Italy) was defined as a national priority contaminated site due to pollution from a petrochemical complex. This study is aimed at addressing the influence of the petrochemical complex on the health profile of residents in Gela. METHODS: Trend analysis by gender was performed for mortality for all diseases and malignant cancers, in the period 1980-2014 for residents in the municipality of Gela, by directly standardized rates and Joinpoint regressions, using, as a reference population, people resident in the Sicily region. SMRs were computed for 5-year periods in the same timespan. Since the beginning of the period analyzed, the share of population of Gela represents 1.5% of total residents in Sicily. Cancer incidence was analyzed for the period 2007-2012 applying a hierarchical Bayesian model to estimate Standardized Incidence Ratios (SIR). Ranks of these ratios were computed to highlight the most incident diseases affecting the population. Malignant neoplasms of lung, stomach and colon were selected because of a priori interest, as they are associated, in etiological terms, with the main contaminants found in the area. Malignant neoplasms of liver, pancreas and larynx were selected as "control diseases" since they share the same main risk factors (smoke and alcohol consumption) of neoplasms of a priori interest, but are not associated with the priority index contaminants identified in Gela. RESULTS: Mortality rates for all causes combined in both genders in Gela decreased over time, but they were higher than those of the whole Sicilian population. The trend of mortality rates due to all malignant cancers increased in men, especially from 1980 to 1987. This result was confirmed by the Joinpoint regression (annual percentage change (APC) 9.8). SMRs analysis showed significant excesses in mortality due to all diseases for both genders compared to the reference population. Other excesses were observed for mortality due to malignant cancers in men and for circulatory diseases in women. The trend for cancers in women in Gela increased from the mid-nineties but less than in men. SIR estimates were higher than 1 for all the diseases analyzed and in both sexes, and their ranks highlighted that cancer sites of a priori interest hold higher positions than "control diseases", although credibility intervals overlapped. CONCLUSIONS: Results highlight that the health profile of residents in Gela is worse than the one of the reference population. Moreover, cancer incidence is in excess in all the sites analyzed and mortality due to all cancers combined has a trend compatible with a cumulative impact due to petrochemical contamination.

Multi-morbidity and frailty at death: A new classification of death records for an ageing world.

Mortality statistics based on underlying cause of death are challenged by increased life expectancy and the growing share of population reaching ages associated with frequent multi-morbidity (with death likely resulting from interactions between multiple diseases). We provide a novel way of analysing causes of death: accounting for all causes mentioned on death certificates and summarizing this information along two dimensions emblematic of ageing populations-multi-morbidity and frailty. We implement this classification for all deaths at ages 50+ in Italy in 2014. Multi-morbid processes represent the majority of deaths, rising from 43 per cent at ages 50-54 to 63 per cent at ages 85-89. Multi-morbidity at death is more frequent among males, although age patterns are identical for both sexes. About one in four deaths involves frailty symptoms, rising to 45 per cent at ages 95+. Mortality rates involving frailty are very similar for both sexes. Supplementary material is available for this article at: https://doi.org/10.1080/00324728.2020.1820558.

Health profiles and socioeconomic characteristics of nonagenarians residing in Mugello, a rural area in Tuscany (Italy).

BACKGROUND: Health, as defined by the WHO, is a multidimensional concept that includes different aspects. Interest in the health conditions of the oldest-old has increased as a consequence of the phenomenon of population aging. This study investigates whether (1) it is possible to identify health profiles among the oldest-old, taking into account physical, emotional and psychological information about health, and (2) there are demographic and socioeconomic differences among the health profiles. METHODS: Latent Class Analysis with covariates was applied to the Mugello Study data to identify health profiles among the 504 nonagenarians residing in the Mugello district (Tuscany, Italy) and to evaluate the association between socioeconomic characteristics and the health profiles resulting from the analysis. RESULTS: This study highlights four groups labeled according to the posterior probability of determining a certain health characteristic: "healthy", "physically healthy with cognitive impairment", "unhealthy", and "severely unhealthy". Some demographic and socioeconomic characteristics were found to be associated with the final groups: older nonagenarians are more likely to be in worse health conditions; men are in general healthier than women; more educated individuals are less likely to be in extremely poor health conditions, while the lowest-educated are more likely to be cognitively impaired; and office or intellectual workers are less likely to be in poor health conditions than are farmers. CONCLUSIONS: Considering multiple dimensions of health to determine health profiles among the oldest-old could help to better evaluate their care needs according to their health status.

Understanding Health Deterioration and the Dynamic Relationship between Physical Ability and Cognition among a Cohort of Danish Nonagenarians.

This study aims to determine how demographics, socioeconomic characteristics, and lifestyle affect physical and cognitive health transitions among nonagenarians, whether these transitions follow the same patterns, and how each dimension affects the transitions of the other. We applied a multistate model for panel data to 2262 individuals over a 2-year follow-up period from the 1905 Danish Cohort survey. Within two years from baseline, the transition probability from good to bad physical health-ability to stand up from a chair-was higher than dying directly (29% vs. 25%), while this was not observed for cognition (24% vs. 27%) evaluated with Mini-Mental State Examination-a score lower than 24 indicates poor cognitive health. Probability of dying either from bad physical or cognitive health condition was 50%. Health transitions were associated with sex, education, living alone, body mass index, and physical activity. Physical and cognitive indicators were associated with deterioration of cognitive and physical status, respectively, and with survivorship from a bad health condition. We conclude that physical and cognitive health deteriorated differently among nonagenarians, even if they were related to similar sociodemographic and lifestyle characteristics and resulted dynamically related with each other.

Obesity-related mortality in France, Italy, and the United States: a comparison using multiple cause-of-death analysis.

OBJECTIVES: We investigate the reporting of obesity on death certificates in three countries (France, Italy, and the United States) with different levels of prevalence, and we examine which causes are frequently associated with obesity. METHODS: We use cause-of-death data for all deaths at ages 50-89 in 2010-2011. Since obesity may not be the underlying cause (UC) of death, we compute age- and sex-standardized death rates considering all mentions of obesity (multiple causes or MC). We use cluster analyses to identify patterns of cause-of-death combinations. RESULTS: Obesity is selected as UC in no more than 20% of the deaths with a mention of obesity. Mortality levels, whether measured from the UC or the MC, are weakly related to levels of prevalence. Patterns of cause-of-death combinations are similar across the countries. In addition to strong links with cardiovascular diseases and diabetes, we identify several less familiar associations. CONCLUSIONS: Considering all mentions on the deaths certificates reduces the underestimation of obesity-related mortality based on the UC only. It also enables us to describe the various mortality patterns involving obesity.

Educational differentials in disability vary across and within welfare regimes: a comparison of 26 European countries in 2009.

BACKGROUND: Social differentials in disability prevalence exist in all European countries, but their scale varies markedly. To improve understanding of this variation, the article focuses on each end of the social gradient. It compares the extent of the higher disability prevalence in low social groups (referred to as disability disadvantage) and of the lower prevalence in high social groups (disability advantage); country-specific advantages/disadvantages are discussed regarding the possible influence of welfare regimes. METHODS: Cross-sectional disability prevalence is measured by longstanding health-related activity limitation (AL) in the 2009 European Statistics on Income and Living Conditions (EU-SILC) across 26 countries classified into four welfare regime groups. Logistic models adjusted by country, age and sex (in all 30-79 years and in three age-bands) measured the country-specific ORs across education, representing the AL-disadvantage of low-educated and AL-advantage of high-educated groups relative to middle-educated groups. RESULTS: The relative AL-disadvantage of the low-educated groups was small in Sweden (eg, 1.2 (1.0-1.4)), Finland, Romania, Bulgaria and Spain (youngest age-band), but was large in the Czech Republic (eg, 1.9 (1.7-2.2)), Denmark, Belgium, Italy and Hungary. The high-educated groups had a small relative AL-advantage in Denmark (eg, 0.9 (0.8-1.1)), but a large AL-advantage in Lithuania (eg, 0.5 (0.4-0.6)), half of the Baltic and Eastern European countries, Norway and Germany (youngest age-band). There were notable differences within welfare regime groups. CONCLUSIONS: The country-specific disability advantages/disadvantages across educational groups identified here could help to identify determining factors and the efficiency of national policies implemented to tackle social differentials in health.

After the epidemiologic transition: a reassessment of mortality from infectious diseases among over-65s in France and Italy.

OBJECTIVES: To assess more accurately the contribution of infectious diseases (IDs) to mortality at age 65+. METHODS: We use cause-of-death data for France and Italy in 2009. In addition to chapter I of the 10th International Classification of Diseases (ICD-10), our list of IDs includes numerous diseases classified in other chapters. We compute mortality rates considering all death certificate entries (underlying and contributing causes). RESULTS: Mortality rates at age 65+ based on our extended list are more than three times higher than rates based solely on ICD-10 chapter I. IDs are frequently contributing causes of death. In France, the share of deaths at age 65+ involving an ID as underlying cause increases from 2.1 to 7.3 % with the extended list, and to 20.8 % when contributing causes are also considered. For Italy, these percentages are 1.4, 4.2 and 18.7 %, respectively. CONCLUSIONS: Publicly available statistics underestimate the contribution of IDs to the over-65s' mortality. Old age is a risk factor for IDs, and these diseases are more difficult to treat at advanced ages. Health policies should develop targeted actions for that population.

Mortality from Alzheimer's disease, Parkinson's disease, and dementias in France and Italy: a comparison using the multiple cause-of-death approach.

OBJECTIVE: We perform an in-depth analysis of all death certificates collected in France and Italy with an entry of Parkinson's disease (PD), Alzheimer's disease (AD), or another dementia. METHOD: Data are for 2008. We measure how frequently these conditions are the underlying cause of death. We then examine what other causes are reported on the certificates. RESULTS: In both countries, AD is the underlying cause for about 6 in 10 certificates with an AD entry. The proportion is lower for PD and dementia, but higher in France than in Italy. Many contributing causes reflect the circumstances surrounding the end of life in AD, PD, and dementia, often characterized by bed confinement and frailty. DISCUSSION: Our research highlights several consequences of the conditions under study that could be targeted by public health policy. It also speaks to the existence of differences in diagnosis/certification practices that may explain differences in mortality levels.

Why do Italian people rate their health worse than French people do? An exploration of cross-country differentials of self-rated health.

The prevalence of bad self-rated health (SRH) varies considerably across countries. Here we present the results of a cross-national comparative study based on the data of National Health Surveys conducted in France and Italy. According to these data, 11% of the Italian and 6% of the French adult population aged between 45 and 74 rate their health as bad or very bad. This gap may result from differences in population structure regarding the individual characteristics (sociodemographic characteristics, diseases and disabilities, lifestyle, and others) that impact on SRH i.e., a structural effect. It may also be that the link between these characteristics and SRH is "country-specific" i.e., a contextual effect. We use logistic regression models to assess the contribution of both explanations. We find that the structural effect plays a prominent role in the higher prevalence of bad SRH in Italy compared to France.