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Background: Following the development of gender medicine in the past 20 years, more recently in the field of oncology an increasing amount of evidence suggests gender differences in the epidemiology of cancers, as well as in the response and toxicity associated with therapies. In a gender approach, critical issues related to sexual and gender minority (SGM) populations must also be considered., Materials and Methods: A working group of opinion leaders approved by the Italian Association of Medical Oncology (AIOM) has been set up with the aim of drafting a shared document on gender oncology. Through the 'consensus conference' method of the RAND/University of California Los Angeles (UCLA) variant, the members of the group evaluated statements partly from the scientific literature and partly produced by the experts themselves [good practice points (GPPs)], on the following topics: (i) Healthcare organisation, (ii) Therapy, (iii) Host factors, (iv) Cancer biology, and (v) Communication and social interventions. Finally, in support of each specific topic, they considered it appropriate to present some successful case studies., Results: A total of 42 articles met the inclusion criteria, from which 50 recommendations were extracted. Panel participants were given the opportunity to propose additional evidence from studies not included in the research results, from which 32 statements were extracted, and to make recommendations not derived from literature such as GPPs, four of which have been developed. After an evaluation of relevance by the panel, it was found that 81 recommendations scored >7, while 3 scored between 4 and 6.9, and 2 scored below 4., Conclusions: This consensus and the document compiled thereafter represent an attempt to evaluate the available scientific evidence on the theme of gender oncology and to suggest standard criteria both for scientific research and for the care of patients in clinical practice that should take gender into account., Competing Interests: Disclosure RB grants or contracts from any entity: Roche, Pfizer, AZ, to institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Gilead, Seagen, GSK, Eisai, BMS, Lilly, MSD, Boeringher. TV reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Helaglobe/Recordati, Astrazeneca; support for attending meetings and/or travel: Sanofi-Regeneron; participation on a Data Safety Monitoring Board or Advisory Board: Takeda; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Regional Referent for GISEG (Italian Group Health and Gender). FP reports institutional research grants from: BMS, Incyte, Agenus, Amgen, Lilly and AstraZeneca; personal fees from: BMS, MSD, Amgen, Merck-Serono, Pierre-Fabre, Servier, Bayer, Takeda, Astellas, Johnson & Johnson, Rottapharm, Ipsen, AstraZeneca, GSK, Daiichi-Sankyo, Seagen. SC is the President of AIOM Foundation (Italian Association of Medical Oncology). The remaining authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: An extensive, albeit contrasting literature has suggested a possible role for orthostatic hypotension as a risk factor for cardiovascular (CVD) and non-CVD mortality, while no data are available for orthostatic hypertension. We investigated whether orthostatic changes in blood pressure (BP) were associated with any increased risk of all-cause, CVD or non-CVD mortality in a group of elderly people., Methods: Two thousand seven hundred and eighty six community-dwelling older participants were followed for 4.4 years. Participants were grouped according to whether they had a drop ≤20 mm Hg in systolic, or ≤10 mm Hg in diastolic BP (orthostatic hypotension), an increase in mean orthostatic systolic BP ≥20 (orthostatic hypertension), or normal changes within 3 minutes of orthostatism., Results: During follow-up, 640 subjects died, 208 of them for CVD-related reasons. Adjusted Cox's regression analysis revealed that, compared with normal changes, orthostatic hypertension was associated with higher all-cause (HR = 1.23; 95% CI: 1.02-1.39) and CVD-related mortality (HR = 1.41; 95% CI: 1.08-1.74), while orthostatic hypotension was only associated with a higher non-CVD mortality (HR = 1.19; 95% CI: 1.01-1.60). Orthostatic hypertension emerged as a predictor of all-cause mortality for: participants over 75 years old; participants with a BMI below 25 kg/m2; participants with no CVD or disabilities; and those taking less than three medications. Orthostatic hypertension also predicted CVD-related mortality in individuals with no hypertension, heart failure, coronary artery disease, or atrial fibrillation., Conclusions: Orthostatic hypertension and hypotension both seem to be relevant risk factors for mortality in the elderly, orthostatic hypertension correlating with all-cause and CVD-related mortality and orthostatic hypotension with non-CVD mortality., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To explore the independent and combined clinical validity of estimated glomerular filtration rate (eGFR) and proteinuria on predicting all-cause and cardiovascular mortality in an Italian elderly population., Methods: Baseline eGFR and proteinuria, all-cause and cardiovascular mortality during a mean follow-up time of 4.4 years were evaluated in 3063 subjects aged 65 years and older of the Progetto Veneto Anziani (Pro.V.A.) Study., Results: Subjects with eGFR<60ml/min/1.73m(2) (n=956) presented a higher prevalence of proteinuria in comparison with those with eGFR≥60ml/min/1.73m(2) (33.8% vs 25.1%, p<0.01). After multivariable adjustment including proteinuria and major diseases, eGFR<60ml/min/1.73m(2) was not associated with increased all-cause mortality. After multivariable adjustment including eGFR and major diseases, proteinuria was associated with all-cause mortality in overall subjects (HR=1.43, 95% CI 1.15-1.78, p<0.01), and in both sexes. After multivariable adjustment both eGFR<60ml/min/1.73m(2) (HR=1.68, 95% CI 1.02-2.78, p=0.04), and proteinuria (HR=2.07, 95% CI 1.31-3.27, p<0.01) were associated with increased cardiovascular mortality. Subjects with both impaired eGFR and presence of proteinuria showed a higher risk for both all-cause and cardiovascular mortality compared to those with normal eGFR and absence of proteinuria., Conclusion: In this general Italian elderly population proteinuria is an independent predictor of all-cause and cardiovascular mortality, while eGFR is not an independent predictor of all-cause mortality, and it is nominally significantly associated with cardiovascular mortality. However, mortality risk is higher in individuals with combined reduced eGFR and proteinuria., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To undertake an epidemiological survey of the prevalence of radiological chondrocalcinosis (CC) of the lower limbs in the elderly Italian population of the Pro.V.A. study., Methods: Knee and pelvic basin radiographs were performed on 3099 subjects aged 65 and older, residing in the Veneto Region of Italy (Rovigo and Camposampiero areas). Two readers independently analysed the knee, coxofemoral and pubic symphysis x-rays of a consecutive sample of 1629 subjects according to Altman. Some laboratory indexes, such as serum parathyroid hormone (PTH), vitamin D (vit D), bone alkaline phosphatase (bALP), deyidroepiandrosterone (DHEA), urinary CrossLaps (XL), and inflammatory biomarkers were evaluated. Quantitative variables were summarised as mean + or - standard deviation and qualitative ones as distributions. Unpaired t-test was used to compare mean values among groups for normally distributed variables, and non-parametric Mann-Whitney test for non normal variables., Results: CC was found in 169 (mean age 78.2 + or - 8.0 yrs) out of the 1629 subjects studied (10.4%). After adjusting for the sex and age structure of the target population, the prevalence was 10.0%. CC was more often observed in women than in men (M: 7.0%; F: 12.8%, p=0.0002), and increased in occurrence with age, rising from 7.8% in subjects aged 65-74 yrs, to 9.4% in those aged 75-84 yrs, and to 21.1% in subjects older than 85 yrs. The knee was the most prevalent location since it was affected in 94.1% of all the subjects with CC, in particular the right limb. Knee CC was bilateral in 71.7% of the affected patients. The occurrence of rheumatic disorders did not differ significantly between the subjects with CC and those without (rheumatoid arthritis 0.59% vs. 0.48%, p=ns)., Conclusions: Although the detection of CC was limited to few joints with the knee being the most affected location, our study confirms the frequent presence of CC at different sites, in keeping with the possible role of systemic factors. Articular CC is an age-related disorder, which could partly explain the prevalence discrepancies reported by various studies. The prevalence of CC found in our survey based on standardised x-ray reading was high, suggesting that CC could be an underdiagnosed disease in the absence of radiographic investigation.

The prevalence of atrial fibrillation (AF) is increasing in older patients faster than that of any other arrhythmia. AF is associated with increased morbidity and mortality. Data on AF in European populations are scarce. The aim of this study was to determine the prevalence and potential predictors of AF and to assess its impact on physical function and mortality in a representative sample of an Italian population >or=65 years of age. One thousand five hundred ninety-nine participants in the Pro.V.A. study, an observational cohort study of Italian subjects >or=65 years old, were assessed for health status, disability, and presence of AF at baseline and at a 4-year follow-up visit. After weighting, prevalence of AF at baseline was 7.4% and increased with advancing age. In subjects with AF, prevalences of stroke, coronary heart disease, peripheral artery disease, cognitive impairment, and physical disability were significantly higher (p <0.01) than in those without AF. In patients with AF, 34% had heart failure compared to 5.3% of those without AF (p <0.0001). In multivariate logistic regression, heart failure was associated with a fivefold risk of AF (odds ratio 5.09, 95% confidence interval 3.20 to 8.11). In Cox analysis, AF was an independent risk factor for mortality. After adjustment for potential confounders, the hazard ratio for mortality associated with AF was 1.47 (95% confidence interval 1.08 to 1.99). In conclusion, in subjects >or=65 years old, AF is strongly associated with heart failure, is an independent risk factor for mortality, and, in the presence of physical disability, could be considered a severity measurement of disability.

Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1 *15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1, DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1 *15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1 *01, DQB1 *05 and HLA-DQA1 *01,DQB1 *06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity.

Background: White matter lesions (WMLs) are associated with hypertension, an increased risk of falling, and impaired physical and cognitive performance that may affect the mechanical effect of falls., Methods: We hypothesized that WMLs are a risk factor for hip fracture (HF). We studied a sample of 820 community-dwelling Italian persons 65 years and older from the cohort of the Progetto Veneto Anziani Study who underwent brain magnetic resonance imaging at baseline. Subjects were classified as having no lesions, focal lesions, or diffuse WMLs., Results: Compared with those with no lesions, participants with diffuse WMLs were older, reported more falls, and had worse physical and cognitive performance, all factors implicated in the causal pathway to HF. During 9 years of follow-up, 51 HFs occurred. Hip fracture risk associated with diffuse WMLs markedly differed between participants younger than 80 years vs those 80 years and older. After adjustment among participants younger than 80 years, diffuse WMLs compared with no lesions were associated with a 2.7-fold (95% confidence interval, 1.1-7.1) increase in the risk of HF. Focal lesions were not statistically significantly associated with an increased risk of HF in the same age group (hazard ratio, 2.0; 95% confidence interval, 0.6-7.6). No associations between diffuse WMLs, focal lesions, and HF were evident among participants 80 years and older, possibly because of the limited sample size., Conclusions: White matter lesions represent an independent risk factor for HF in persons younger than 80 years. Older persons with diffuse WMLs should be considered candidates for multifactorial interventions aimed at reducing the risk of falling and fractures.

In this study, 153 Italian centenarians from four different geographical areas, including Modena (northern Italy), Ancona (central Italy), Perugia (central Italy) and Sardinia island (AKEA Project) were enrolled. Plasma levels of vitamin C, uric acid, vitamin A and vitamin E as well as the activities of superoxide dismutase and glutathione peroxidase were measured. Subjects were compared to a younger control population of the same areas, divided into three age groups:

Objective: Tooth loss impacts on general health and is a risk factor for malnutrition, disability, loss of self-sufficiency, and deterioration in quality of life. The present study was carried out to evaluate the prevalence of edentulism and its association with social and lifestyle factors in a population of elderly Italians., Material and Methods: Dental, social, and disease conditions were evaluated in a large community-based cohort (3054) of elderly subjects (> or =65 years) of both sexes in northern Italy. Logistic regression analyses with stepwise forward selection were performed to estimate the independent contribution of nutritional, socio-economic, and lifestyle variables to dental status. Adjusted ORs and 95% CI were estimated for variables significantly associated with edentulism., Results: The prevalence of edentulism was about 44.0%. It was more pronounced in females and it was twice as prevalent in the 90+ years age group. Among edentulous subjects, 17.5% wore no prostheses. Difficulties in chewing and in swallowing were reported by 47.6% and 13.7% of the subjects, respectively. Multivariate analysis indicates that edentulism was associated with age in both sexes. For women, independently associated risk factors were: years since menopause >23 (OR = 1.81; 95% CI: 1.37-2.40), number of children >3 (OR = 1.95; 95% CI: 1.36-2.80), and living alone (OR = 1.47; 95% CI: 1.15-1.88). For men, these were serum albumin <40 g/l (OR = 1.79; 95% CI: 1.22-2.63), current smoking (OR = 4.01; 95% CI: 2.59-6.20), and former smoking (OR = 3.42; 95% CI: 2.42-4.82)., Conclusions: The prevalence of edentulism among the elderly Italian population studied was at the high end among Western countries, and higher in women than in men. In women, tooth loss correlated with aging, female events (pregnancies, menopausal status), and living alone. In men, aging and smoking are important determinants of edentulism, which is associated with the risk condition of hypoalbuminemia. Difficulty in chewing was associated with dentition type. In our study, the high prevalence of edentulous subjects without prostheses suggests a need for educational and social measures to improve patients' attitudes to dental care and to encourage the use of prostheses among the elderly.

This paper aims to discuss the validation and family determinants affecting the longevity of Sardinian centenarians, using a genealogical approach. This preliminary study presents the first results of a genealogical tree reconstruction of selected centenarians aged 105 and over, from certain areas. These are mostly situated in the province of Nuoro, an area with the highest rate of centenarians and where the female-to-male sex ratio tends to be male-biased. An accurate centenarian age validation was performed that required a meticulous examination of numerous civil status records and parish registers. An important finding was that longevity occurs among the ascendants of a particular branch of the family. The data used are still provisional but, should it apply to other validated cases, it would provide empirical evidence of a genetic component in longevity. A more thorough examination of the data available may yield deeper insights into the role played by endogamy and consanguinity.

High prevalence and low female/male ratio for validated centenarians are observed in Sardinia and these findings appear to be thus far unique to this island. Moreover a specific region on the island is characterized by exceptional male longevity. We calculated the extreme longevity index (ELI), defined as the percentage of persons born in Sardinia between 1880 and 1900, who became centenarians. A gaussian smoothing method was used in order to identify the so-called 'Blue Zone', where longevity is concentrated in the central-eastern part of the island and covers all the mountainous areas of central Sardinia. The estimated life expectancy in the 'Blue Zone' is longer than in the remaining territory of the island especially for men and the male to female ratio among centenarians born in this area is 1.35 compared to 2.43 in the rest of Sardinia. The specific mechanism by which persons living in this territory were more likely to reach extreme longevity remains unknown but it is interesting to note that most of the 'longevity hot spots' identified in various regions of the world over the years have been located in mountainous geographical areas even if none of these longevity regions have been fully validated. An alternative and interesting hypothesis is that the high rate of inbreeding determined by frequent marriages between consanguineous individuals and low immigration rates have progressively decreased the variability of the genetic pool and facilitated the emergence of genetic characteristics that protect individuals from diseases that are major causes of mortality particularly in older individuals. Given the exceptionally high prevalence of male centenarians in the 'Blue Zone', it is reasonable to assume that either the environmental characteristics or the genetic factors, or both, exert their favorable effect more strongly in men than in women. Thus, the mechanism involved may be modulated by the hormonal milieu, or may be associated with genes located in the sex chromosomes., (Copyright 2004 Elsevier Inc.)

Background and Aims: Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity reside in those polymorphisms for the immune system genes which regulate immune-inflammatory responses, in particular cytokine gene polymorphisms. The frequency of -174C single nucleotide polymorphism (SNP) in the promoter region of the interleukin (IL)-6 gene is increased in Italian male centenarians. Moreover, the frequency of -1082G SNP at the 5' flanking region of the IL-10 gene coding sequence is increased among male centenarians, and that of +874A SNP at the interferon (IFN)-gamma gene was found more frequently in female centenarians. These findings indicate that different alleles at different cytokine gene codings for pro- (IL-6, IFN-gamma) or anti-inflammatory (IL-10) cytokines may affect the individual life-span expectancy, influencing the type and intensity of immune-inflammatory responses against environmental stressors., Methods: In the present study, we analyzed these IL-6, IL-10 and IFN-gamma gene polymorphisms in 112 (36 male, 76 female) centenarians from the island of Sardinia, whose population shows a genetic background quite different from that of mainland Italy, as well as in 137 sixty-year-old controls from the same geographic area., Results: No significant differences were observed on analyzing IL-6, IL-10 and IFN-gamma polymorphism frequencies among centenarians and controls, either on the whole and when the data were analyzed according to gender., Conclusions: These data indicate that gene polymorphisms of cytokines playing a major regulatory role in the inflammatory response do not affect life expectancy in the Sardinian population. Thus, cytokine/longevity associations have a population-specific component, being affected by the population-specific gene pool as well as by gene-environment interactions, behaving as survival rather than longevity genes.

Although heparin-induced thrombocytopenia (HIT) is a known complication of intravenous unfractionated heparin (UFH), its incidence in medical patients treated with subcutaneous UFH is less well defined. To determine the incidence of HIT in this category of patients, the platelet count was performed at baseline and then every 3 +/- 1 days in 598 consecutive patients admitted to 2 medical wards and treated with subcutaneous UFH for prophylactic (n = 360) or therapeutic (n = 238) indications. The diagnosis of HIT was accepted in the case of a platelet drop of 50% or more and either the demonstration of heparin-dependent antibodies or (when this search could not be performed) the combination of the following features: (1) the absence of any other obvious clinical explanation for thrombocytopenia, (2) the occurrence of thrombocytopenia at least 5 days after heparin start, and (3) either the normalization of the platelet count within 10 days after heparin discontinuation or the earlier patient's death due to an unexpected thromboembolic complication. HIT developed in 5 patients (0.8%; 95% CI, 0.1%-1.6%); all of them belonged to the subgroup of patients who received heparin for prophylactic indications. The prevalence of thromboembolic complications in patients with HIT (60%) was remarkably higher than that observed in the remaining 593 patients (3.5%), leading to an odds ratio of 40.8 (95% CI, 5.2-162.8). Although the frequency of HIT in hospitalized medical patients treated with subcutaneous heparin is lower than that observed in other clinical settings, this complication is associated with a similarly high rate of thromboembolic events.

Human longevity may be correlated with optimal functioning of the immune system, suggesting that genetic determinants of longevity also resides in those polymorphisms for the immune system genes that regulate immune responses as histocompatibility (HLA) antigens. However, conflicting results have been obtained. Some well planned and designed association studies performed in Caucasians suggest that longevity is associated with positive selection of alleles (i.e. HLA-DR11) or haplotypes (i.e. HLA-B8,DR3) that confer resistance to infectious diseases, respectively, via peptide presentation or via antigen non-specific control of immune response. Association studies are subjected to a number of possible confounding factors, the homogeneity of the population in term of geographical origin among others. Because of the lack of large-scale heterogeneity, the Sardinians represent a suitable population for association studies addressed to dissect the complex traits as longevity. Thus, we have evaluated, by the amplification refractory mutation system/polymerase chain reaction, HLA-DR frequencies in 120 centenarians (79 women and 41 men) and 86 controls (53 women and 33 men) from Sardinia, to validate, in this very homogeneous population, the associations between HLA alleles or haplotypes and longevity observed in other Caucasoid populations. No significant differences were obtained by analysing the differences between Centenarians and controls except for HLA-DRB1*15 that was increased in centenarians. However, the significance was not maintained by multiplying P values for the number of alleles under study. Thus, in Sardinian centenarians, we were not able to confirm the findings observed in the well planned and designed studies performed in other Caucasoid populations. Besides, HLA HFE gene polymorphisms have been recently demonstrated to be associated with longevity in the Sicilian population but not in Danish one. On the whole these findings clearly show that HLA/longevity associations are population-specific, being heavily affected by the population-specific genetic and environmental history. So, in our opinion, HLA genes might be considered survival genes not longevity genes.

Background and Aims: Environmental, life-style, and dietary factors, including the type of dietary fatty acids consumed, may influence the onset of dementia. The aim of the present study was therefore to examine whether type of dietary fats consumed is associated with cognitive performance., Methods: Using gaschromatography, plasma phospholipid fatty acid composition was determined in a sample of subjects (age > or = 65 years) randomly selected from the general Pro.V.A. study population. Plasma phospholipid fatty acid composition is a reliable marker of the type of fats present in the diet. The subjects' cognitive capacity was tested using the Mini-Mental State Examination (MMSE)., Results: At multiple regression analysis, the MMSE score variance was correlated with age and education level In 30% of cases, whereas the other variables considered (including type of fatty acids consumed) had an almost negligible effect., Conclusions: In free-living elderly subjects, moderate to severe cognitive impairment is not associated with dietary fatty acids.

We have analyzed a sample of 40 centenarians and 116 young controls from Sardinia, with a set of new Y chromosome binary markers, to evaluate if Y chromosome genes are involved in the high prevalence of males among centenarian Sardinians (1/2 vs. 1/4 in other populations studied). The results indicate that none of the seven lineages that account for >97% of the Y chromosome diversity in Sardinia provide an advantage with respect to the extreme longevity. However, our results, although based on the male-specific Y chromosome polymorphisms, give a clear profile of the pattern of genetic variability in Sardinia. Indeed they indicate that the Sardinian population had two main founder populations that have evolved in isolation for at least the last 5,000 years. These findings set the stage for future studies on longevity and other complex traits in Sardinia., (Copyright 2001 S. Karger AG, Basel)

The aging of the Italian population is an emerging public health priority. In 2025 Italy is expected to have the highest world median age with nearly half of the population over 50 years old. To avoid an unbearable burden of disease and disability on future generations, we must identify areas for intensive disease and disability prevention programs. Preliminary results from the PRO.V.A study show that disability is associated with conditions that are potentially preventable as chronic diseases and falls or are treatable as chronic pains. Moreover, it is of extreme interest to identify and understand biological and environmental secrets of successful aging as the AKEA study tries to do and the ways of overcoming disabilities in the extreme limits of life more and more possible to reach.

Mitochondrial DNA (mtDNA) is characterized by high variability, maternal inheritance, and absence of recombination. Studies of human populations have revealed ancestral associated polymorphisms whose combination defines groups of mtDNA types (haplogroups) that are currently used to reconstruct human evolution lineages. We used such inherited mtDNA markers to compare mtDNA population pools between a sample of individuals selected for successful aging and longevity (212 subjects older than 100 years and in good clinical condition) and a sample of 275 younger individuals (median age 38 years) carefully matched as to sex and geographic origin (northern and southern Italy). All nine haplogroups that are typical of Europeans were found in both samples, but male centenarians emerged in northern Italy as a particular sample: 1) mtDNA haplogroup frequency distribution was different between centenarians and younger individuals (P=0.017 by permutation tests); and 2) the frequency of the J haplogroup was notably higher in centenarians than in younger individuals (P=0.0052 by Fisher exact test). Since haplogroups are defined on the basis of inherited variants, these data show that mtDNA inherited variability could play a role in successful aging and longevity.

This paper describes an epidemiological study performed in all centenarians living in Sardinia, a large island located in the Mediterranean sea, 120 Km from the Italian coast. Due to its long-standing isolation, low immigration rate, high endogamy and rather uniform lifestyle, Sardinia offers an ideal setting in which to study the genetic traits associated with extreme longevity and successful aging. A total of 233 potentially eligible centenarians were traced in the entire territory. Of these, 66 died prior to being interviewed, 11 were not found and unknown, and 15 refused to be interviewed. A multidimensional home interview was administered to 141 centenarians, and an equivalent number of 60-year-old controls matched for gender and area of residence. Furthermore, 41 living siblings of the centenarians, and 41 age- and sex-matched controls for these siblings were also studied. The prevalence of centenarians was 13.56 per 100,000, and the female/male ratio was approximately 2. Prevalence and female/male ratio were consistent across the four Sardinian municipalities and are, respectively, higher and lower than those reported in other population-based surveys. A number of methodological problems confronted in doing the field work, and plans for future analysis of this rich dataset are discussed.

Background: In this study, the apolipoprotein E (apoE) genotypes as well as plasma lipid and lipoprotein levels have been determined for the first time in 633 healthy and unrelated inhabitants on the island of Sardinia (291 men and 342 women, age range 6-89 years), randomly selected in the four districts of Sardinia among healthy people having parents and grandparents born in the same geographic area. This island lies in the centre of the western Mediterranean sea with a well-recognized peculiar and preserved genetic background. The epsilon 3 allele frequency (0.897) is higher than that previously reported in southern and mainland Italy and is one of the highest in Europe and among Caucasians; epsilon 2 allele frequency (0.040) is the lowest in Europe; epsilon 4 (0.063) is unusually low and, most interestingly, does not change in the different age groups, i.e. does not decrease in old subjects., Results: Lipid and lipoprotein analysis confirm that total cholesterol and low-density lipoprotein (LDL)-cholesterol levels are lower than those described in mainland Italy; moreover, in this large Sardinian series, accurately selected, epsilon 4 allele did not influence total cholesterol (P = 0.270), LDL-cholesterol (P = 0.667) and high-density lipoprotein (HDL)-cholesterol (P = 0.549) as in other populations. In contrast, subjects carrying the epsilon 2 allele were found to have significantly lower total cholesterol (P = 0.001) and LDL-cholesterol (P = 0.001) levels than epsilon 3 carriers., Conclusion: The low epsilon 4 frequency and the lack of influence of this allele on lipid metabolism is a unique characteristic and, to date, has been described only in Sardinia among Caucasians; it might contribute to the low prevalence of coronary artery disease in this island.

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil.