Clinical Approach in the Management of Paediatric Patients with Familial Hypercholesterolemia: A National Survey Conducted by the LIPIGEN Paediatric Group.

Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3-4 months (29.2% and 23.3%) or 6-12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.

[Identifying possible homozygous familial hypercholesterolemia patients: an Italian experts' opinion]. / Inquadramento diagnostico del paziente con possibile ipercolesterolemia familiare omozigote: il parere di un gruppo italiano di esperti.

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and massive risk of premature atheromasia and cardiovascular events. HoFH is caused by mutations in several genes, such as LDLR, APOB, PCSK9 and LDLRAP1. If untreated, the average age of death is 18 years old, but fatalities within the first 5 years of age have been recorded. Therefore, early diagnosis and treatment are crucial, in order to prevent and/or delay the cardiovascular complications of LDL-C exposure. Because HoFH is a rare disorder, it is not frequently encountered in daily clinical practice at the primary/secondary unspecialized cardiological centers. Then the availability of practical indications helping to identify HoFH patients or to arise a suspect of HoFH is particularly strategic to promptly start the appropriate lipid-lowering therapy. For such a purpose, a group of Italian experts suggests three useful algorithms to identify cases requiring accurate and specialized clinical evaluation as potential HoFH patients. These cases with suspected HoFH should be addressed to specialized centres for the optimal management of these patients.

Tooth retention predicts good physical performance in older adults.

BACKGROUND: Oral health is closely related to both physical and psychological well-being, as it enables individuals to eat, speak, and socialize. The number of teeth is the most used indicator of oral health. Several reports document a relationship of dental status with a variety of indicators of general health but longitudinal studies employing standardized physical performance tests are infrequent in the scientific literature. SUBJECTS AND METHODS: The Italian elderly participating in the Pro.V.A. longitudinal Study (3099 subjects aged 65+ at baseline, 2196 at the 5-year follow-up 1 and 1641 at the 7-year follow- up 2) underwent detailed interview and extensive clinical and instrumental examination that included validated physical performance measures. Participants were classified into 4 groups according to the number of remaining teeth: 0, 1-7, 8-19, and 20+. To explore the association of the number of remaining teeth with physical function and disability, we performed logistic regression analyses with models progressively adjusted for a wide number of covariates, namely anthropometric (gender, age, BMI), comorbidity (cardio-vascular, osteoarticular, and neurological diseases including depression), muscle strength (assessed for upper and lower limbs), lifestyle (smoking status, alcohol use, leisure time activities) and socioeconomical status (education, income, marital status, loneliness). RESULTS: Dental status correlated with most comorbidities, lifestyle, and socio-economic variables at the univariate analysis at baseline and at follow-ups. A good dental status was significantly associated with better physical functioning and lower disability. The presence of 20+ teeth resulted significantly protective (reference group: 0 teeth) versus mobility-related disability (OR = 0.67), disability (OR = 0.54) and inability to perform heavy duties (OR = 0.62), at follow up 1 and low physical performance score (OR = 0.59) at follow up 2. Conversely, the detrimental effect of edentulism, explored in subjects with or without dentures, was present but not as straightforward. Conclusion. The assessment of a geriatric patient should include an oral evaluation as a good dental status is a crucial component of successful aging.

Factors Associated With Functional Decline in Hand and Hip/Knee Osteoarthritis After One Year: Data From a Population-Based Study.

OBJECTIVE: To investigate factors that together with hand or hip/knee osteoarthritis (OA) could contribute to functional decline over a year's time in elderly individuals. METHODS: The data of 1,886 individuals between ages 65 and 85 years in a prospective, observational population-based study with 12-18 months of follow-up in the context of the European Project on Osteoarthritis were analyzed. The outcome measures were self-reported hand and hip/knee functional decline, evaluated using a minimum clinically important difference of 4 on the Australian/Canadian Hand OA Index and of 2 on the Western Ontario and McMaster Universities Osteoarthritis Index hip/knee physical function subscales, both normalized to 0-100. Using regression models adjusted for sex, age, country, and education level, the baseline factors considered were clinical hand or hip/knee OA, pain, analgesic/antiinflammatory medications, comorbidities, social isolation, income, walking time, grip strength, physical activity time, and medical/social care. RESULTS: After a year, 453 participants were identified as having worse hand functionality and 1,389 as not worse. Hand OA, anxiety, walking time, and grip strength were risk factors for hand functional decline; pain was a confounder of the effect of hand OA. Analgesic/antiinflammatory medications mediated the combined effect of hip/knee OA plus pain on functional decline in the 554 individuals classified as having worse hip/knee functionality and the 1,291 persons who were not worse. Peripheral artery disease, obesity, and cognitive impairment were other baseline risk factors. CONCLUSION: Study findings showed that together with emotional status and chronic physical and cognitive conditions, OA affects hand and hip/knee functional decline.

Omega n-3 Supplementation: Exploring the Cardiovascular Benefits Beyond Lipoprotein Reduction.

PURPOSE OF REVIEW: Hypertriglyceridaemia is a highly prevalent disorder worldwide. Genetic and Mendelian randomization studies have suggested that triglyceride (TG)-rich lipoproteins are causal risk factors for coronary heart disease and contribute to the residual cardiovascular risk observed in patients optimally treated with statins. However, clinical trials failed to show cardiovascular benefits of TG-lowering; in this context, trials with omega-3 fatty acids provided contrasting results. Few trials have tested the supplementation of EPA alone rather than the combination of EPA + DHA. The JELIS study showed that EPA 1.8 g/day significantly reduced CV events in hypercholesterolaemic patients given statins, an effect that was independent on lipid reduction. RECENT FINDINGS: The REDUCE-IT trial showed that high-dose (4 g/day) EPA significantly reduces the incidence of major cardiovascular events compared with placebo in patients with elevated TG levels. The clinical benefit was higher than expected by the reduction of TG-rich lipoprotein levels. Recent data support the efficacy of high-dose EPA supplementation on a background of optimal LDL-C-lowering therapy as a key approach to achieve a further and significant reduction of CV events in very-high CV risk patients with persistent hypertriglyceridaemia. The effect on lipids does not appear to fully explain the CV benefit, and additional mechanisms of action of EPA likely contribute to the cardiovascular protection, including the reduction of inflammation and platelet aggregation. Current guidelines recommend using high-dose EPA in combination with a statin in high/very-high CV risk patients with mild-to-moderate elevation of plasma TG to reduce the residual CV risk.

Association Between Osteoarthritis and Social Isolation: Data From the EPOSA Study.

OBJECTIVE: To determine whether there is an association between osteoarthritis (OA) and incident social isolation using data from the European Project on OSteoArthritis (EPOSA) study. DESIGN: Prospective, observational study with 12 to 18 months of follow-up. SETTING: Community dwelling. PARTICIPANTS: Older people living in six European countries. MEASUREMENTS: Social isolation was assessed using the Lubben Social Network Scale and the Maastricht Social Participation Profile. Clinical OA of the hip, knee, and hand was assessed according to American College of Rheumatology criteria. Demographic characteristics, including age, sex, multijoint pain, and medical comorbidities, were assessed. RESULTS: Of the 1967 individuals with complete baseline and follow-up data, 382 (19%) were socially isolated and 1585 were nonsocially isolated at baseline; of these individuals, 222 (13.9%) experienced social isolation during follow-up. Using logistic regression analyses, after adjustment for age, sex, and country, four factors were significantly associated with incident social isolation: clinical OA, cognitive impairment, depression, and worse walking time. Compared to those without OA at any site or with only hand OA, clinical OA of the hip and/or knee, combined or not with hand OA, led to a 1.47 times increased risk of social isolation (95% confidence interval = 1.03-2.09). CONCLUSION: Clinical OA, present in one or two sites of the hip and knee, or in two or three sites of the hip, knee, and hand, increased the risk of social isolation, adjusting for cognitive impairment and depression and worse walking times. Clinicians should be aware that individuals with OA may be at greater risk of social isolation. J Am Geriatr Soc 68:87-95, 2019.

Minimal clinically important decline in physical function over one year: EPOSA study.

BACKGROUND: The Australian/Canadian hand Osteoarthritis Index (AUSCAN) and the Western Ontario and McMaster Universities knee and hip Osteoarthritis Index (WOMAC) are the most commonly used clinical tools to manage and monitor osteoarthritis (OA). Few studies have as yet reported longitudinal changes in the AUSCAN index regarding the hand. While there are published data regarding WOMAC assessments of the hip and the knee, the two sites have always evaluated separately. The current study therefore sought to determine the minimal clinically important difference (MCID) in decline in the AUSCAN hand and WOMAC hip/knee physical function scores over 1 year using anchor-based and distribution-based methods. METHODS: The study analysed data collected by the European Project on Osteoarthritis, a prospective observational study investigating six adult cohorts with and without OA by evaluating changes in the AUSCAN and WOMAC physical function scores at baseline and 12-18 months later. Pain and stiffness scores, the performance-based grip strength and walking speed and health-related quality of life measures were used as the study's anchors. Receiver operating characteristic curves and distribution-based methods were used to estimate the MCID in the AUSCAN and WOMAC physical function scores; only the data of those participants who possessed paired (baseline and follow up-measures) AUSCAN and WOMAC scores were included in the analysis. RESULTS: Out of the 1866 participants who were evaluated, 1842 had paired AUSCAN scores and 1845 had paired WOMAC scores. The changes in the AUSCAN physical function score correlated significantly with those in the AUSCAN pain score (r = 0.31). Anchor- and distribution-based approaches converged identifying 4 as the MCID for decline in the AUSCAN hand physical function. Changes in the WOMAC hip/knee physical function score were significantly correlated with changes in both the WOMAC pain score (r = 0.47) and the WOMAC stiffness score (r = 0.35). The different approaches converged identifying two as the MCID for decline in the WOMAC hip/knee physical function. CONCLUSIONS: The most reliable MCID estimates of decline over 1 year in the AUSCAN hand and WOMAC hip/knee physical function scores were 4 and 2 points, respectively.

Reduced incidence of cardiovascular events in hyper-Lp(a) patients on lipoprotein apheresis. The G.I.L.A. (Gruppo Interdisciplinare Aferesi Lipoproteica) pilot study.

BACKGROUND: Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of Familial Hypercholesterolemia, Familial Combined Hypercholesterolemia, resistant/intolerant to lipid lowering drugs, and hyper-lipoproteinemia(a). Lipoprotein(a) [Lp(a)] has been classified as the most prevalent genetic risk factor for coronary artery disease and aortic valve stenosis. AIM: Our multicenter retrospective study has the aim to analyze the incidence of adverse cardiovascular events (ACVE) before and during the LA treatment, in subjects with elevated level of Lp(a) (>60 mg/dL) [hyper-Lp(a)] and chronic ischemic heart disease. METHODS: We collected data of 23 patients (mean age 63 ± 9 years, male 77%; from hospital of Pisa 11/23, Pistoia 7/23, Verona 2/23, Padova 2/23 and Ferrara 1/23), with hyper-Lp(a), pre-apheresis LDL-cholesterol <100 mg/dL, cardiovascular disease, on maximally tolerated lipid lowering therapy and LA treatment (median 7 years, interquartile range 3-9 years). The LA treatment was performed by heparin-induced LDL precipitation apheresis (16/23), dextran-sulphate (4/23), cascade filtration (2/23) and immunoadsorption (1/23). The time lapse between first cardiovascular event and beginning of apheresis was 6 years (interquartile range 1-12 years). RESULTS: The recorded ACVE, before and after the LA treatment inception, were 40 and 10 respectively (p < 0.05), notably, the AVCE rates/year were 0.43 and 0.11 respectively (p < 0.05) with a 74% reduction of event occurrence. CONCLUSIONS: Our data confirm long-term efficacy and positive impact of LA on morbidity in patients with hyper-Lp(a) and chronic ischemic heart disease on maximally tolerated lipid lowering therapy.

Difficulties with Fine Motor Skills and Cognitive Impairment in an Elderly Population: The Progetto Veneto Anziani.

OBJECTIVES: To investigate dysfunction in fine motor skills in a cohort of older Italian adults, identifying their prevalence and usefulness as indicators and predictors of cognitive impairment. DESIGN: Population-based longitudinal study with mean follow-up of 4.4 years. SETTING: Community. PARTICIPANTS: Older men and women enrolled in the Progetto Veneto Anziani (Pro.V.A.) (N = 2,361); 1,243 subjects who were cognitively intact at baseline were selected for longitudinal analyses. MEASUREMENTS: Fine motor skills were assessed by measuring the time needed to successfully complete two functional tasks: putting on a shirt and a manual dexterity task. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score less than 24. RESULTS: On simple correlation, baseline MMSE score was significantly associated with the manual dexterity task (correlation coefficient (r) = -0.25, P < .001) and time needed to put on a shirt (r = -0.29, P < .001). Over the study period, changes in time needed to perform the fine motor tasks were significantly associated with changes in MMSE (putting on a shirt: ß = 0.083, P = .003; manual dexterity task: ß = 0.098, P < .001). Logistic regression analyses confirmed that worse results on tasks were associated with cognitive impairment at baseline (odds ratio (OR) = 2.47, 95% confidence interval (CI) = 1.74-3.50, for the fourth quartile of time needed to put on a shirt; OR = 1.98, 95% CI = 1.42-2.76, for the fourth manual dexterity task quartile) and greater risk of cognitive impairment developing during follow-up (OR = 4.38, 95% CI = 2.46-7.80, for the fourth quartile of time needed to put on a shirt; OR = 2.20, 95% CI = 1.30-3.72, for the fourth manual dexterity task quartile). CONCLUSIONS: Difficulties with fine motor skills are common in older adults, and assessing them may help to identify early signs of dementia, subjects at high risk to develop cognitive decline, and individuals who can be referred to specialists.

Autosomal Recessive Hypercholesterolemia: Long-Term Cardiovascular Outcomes.

BACKGROUND: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. OBJECTIVES: Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. METHODS: Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. RESULTS: We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years of age; baseline LDL-C: 571.9 ± 171.7 mg/dl). During a mean follow-up of 14.1 ± 7.3 years, there was a significant increase in the use of high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in 6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 ± 85.1 mg/dl (-69.6% from baseline), with a better response in patients taking lomitapide (-88.3%). Overall, 23.1% of ARH patients reached LDL-C of <100 mg/dl. During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%, respectively). No incident stroke was observed. Age (≥30 years) and the presence of coronary artery disease at diagnosis were the major predictors of incident ASCVD. CONCLUSIONS: Despite intensive treatment, LDL-C in ARH patients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking.

The effect of childcare activities on cognitive status and depression in older adults: gender differences in a 4.4-year longitudinal study.

OBJECTIVES: Although involvement in childcare activities seems to promote better physical and mental health in older adults, its impact on cognitive status and depression has not yet been fully elucidated. We aimed to analyze the association between engagement in childcare activities and cognitive and psychological status over a 4.4-year period in community-dwelling older adults. METHODS: Two thousand one hundred four subjects older than 65 years without severe cognitive impairment at baseline were categorized according to the frequency of their involvement in childcare activities (everyday, occasionally, never). The participants' cognitive status and depressive symptoms were evaluated at baseline and after 4.4 years. RESULTS: During the follow-up, 269 (12.8%) new cases of cognitive impairment and 229 (10.9%) new cases of depression were registered. Men engaged in childcare showed an almost 20% lower risk of cognitive impairment and cognitive decline. Women demonstrated similar results, except for those occasionally involved in childcare, who had a higher risk of cognitive decline compared with women who never engaged in it. The risk of developing depression was reduced in men involved daily (OR = 0.44, 95% CI: 0.30-0.62, p < 0.0001) and occasionally in childcare, who also demonstrated a lower risk of exacerbating depressive symptoms compared with subjects who never involved in it. The onset of depression was reduced in women occasionally engaged in childcare (OR = 0.68, 95% CI: 0.56-0.82, p < 0.0001), but not significantly in those daily involved in it. CONCLUSIONS: Involvement of older adults in childcare activities seems to lower the risk of cognitive impairment in both genders and to prevent onset or worsening of depression particularly in older men. Copyright © 2017 John Wiley & Sons, Ltd.

Anthropometric parameters and the incidence of atrial fibrillation in older people: the PRO.V.A study.

BACKGROUND: Atrial fibrillation (AF) has been associated with body size and central obesity, but the impact of different anthropometric measures in this relationship has been inadequately investigated. HYPOTHESIS: In this study, we examined the association between baseline anthropometric parameters with the incidence of AF in older people, hypothesizing that body size could impact the onset of AF more than fat distribution. METHODS: Our study included 1764 participants with a mean age of 74.3 ± 6.9 years and no AF at baseline. Body mass index (BMI), body height, body surface area (BSA), waist and hip circumference, waist-to-stature ratio, waist-to-hip ratio, and mid-upper arm circumference (MUAC) were measured by trained physicians. AF was assessed after a 4.4-year follow-up. RESULTS: There were 115 new cases of AF observed after the follow-up. Taking lower values of these measures for reference, the adjusted AF risk was 2.42 (95% confidence interval [CI]:1.88-3.12) for the highest stature quartile, 1.36 (95% CI:1.15-1.62) for BMI ≥30 kg/m2 , 2.12 (95% CI:1.73-2.59) for the highest BSA quartile, 1.38 (95% CI: 1.21-1.56) for higher MUAC, and 1.39 (95% CI: 1.23-1.58, P < 0.0001) for higher hip circumference values. Central obesity did not seem to relevantly predict the onset of AF in our sample. Stature revealed the strongest impact on the onset of AF (5% higher risk of developing AF per 1 cm increase in height). CONCLUSIONS: Body size, particularly tall stature and obesity, but not fat distribution, seems to be associated with the risk of AF in the elderly.

Poor Physical Performance Predicts Future Onset of Depression in Elderly People: Progetto Veneto Anziani Longitudinal Study.

BACKGROUND: Reduced physical performance is predictive of deleterious outcomes in older adults. Data considering objective physical performance and incident depression are sparse. OBJECTIVE: The objective of this study was to investigate during a 4-year study whether objective physical performance can predict incident depression among older adults who do not have depression at the baseline. DESIGN: This was a longitudinal study. METHODS: From 3,099 older people initially enrolled in the Progetto Veneto Anziani study, 970 participants without depression at the baseline were included (mean age = 72.5 years; 54.6% women). Physical performance measures included the Short Physical Performance Battery, 4-m gait speed, Five-Times Sit-to-Stand test, leg extension and flexion, handgrip strength, and 6-minute walk test, categorized in sex-specific tertiles. Depression was classified on the basis of the Geriatric Depression Scale and a diagnosis from a geriatric psychiatrist. Area under the curve and logistic regression analyses were conducted. RESULTS: At the baseline, participants developing depression during the follow-up (n = 207) scored significantly worse across all physical performance measures than those who did not develop depression. The area under the curve and predictive power were similar for all of the physical performance tests assessed. In the logistic regression analysis, after adjustment for 14 potential confounders, worse physical performance across all tests increased the risk of depression. Participants in the lowest tertile of the Short Physical Performance Battery were at notable odds of developing depression (odds ratio = 1.79; 95% CI = 1.18-2.71). The association between poor physical performance and depression was typically stronger in women than in men, except for 4-m gait speed. LIMITATIONS: No gold standard was used for a depression diagnosis; oxidative stress and inflammatory markers were not included; and there was a high rate of missing data at the follow-up. CONCLUSIONS: Low physical performance appeared to be an independent predictor of depression over a 4-year follow-up in a sample of elderly people.

Changes in Frailty Status and Risk of Depression: Results From the Progetto Veneto Anziani Longitudinal Study.

OBJECTIVE: To evaluate whether prefrailty was associated with the risk of developing depression and if longitudinal changes in frailty status corresponded to changes in incident depression during follow up. METHODS: A population-based, prospective cohort study was conducted for 4.4 years in two separate geographic areas near the city of Padua in the Veneto Region of Northern Italy. In 891 nondepressed, nonfrail, community-dwelling Italian subjects aged ≥ 65 (46.6% men) belonging to the Progetto Veneto Anziani study, depression was defined according to the Geriatric Depression Scale and was confirmed by geriatricians skilled in psychogeriatric medicine. Prefrailty was defined by the presence of one or two criteria among the Fried criteria. RESULTS: The incidence rate of depression was 13.3% among subjects improving their frailty status at follow-up (N = 15), 15.0% in those who remained stable (N = 79), and 26.7% among worsening participants (N = 67) (p = 0.001). Prefrailty at baseline did not predict the onset of depression (HR: 0.82; 95% CI: 0.55-1.21; Wald χ2 = 0.73; df = 1; p = 0.43), but a deterioration during follow-up in at least one additional frailty criteria was associated with a significantly higher risk (HR: 1.95; 95% CI: 1.32-2.89; Wald χ2 = 5.78; df = 2; p = 0.01). Improvement in frailty status was not associated with the risk of incident depression (HR: 0.71; 95% CI: 0.35-1.42; Wald χ2 = 0.47; df = 2; p = 0.28). CONCLUSION: Our data did not offer evidence that prefrailty per se predisposes to the onset of depression, but worsening in frailty status is associated with an almost twofold increased risk of incident depression, irrespective from the initial level of impairment.

Results of an Observational Cohort Study of Hyperuricemia as a Predictor of Poor Physical Performance in the Elderly.

OBJECTIVE: Hyperuricemia is frequent in older people and associated with several medical conditions. The relationship between hyperuricemia and physical performance is limited. We aimed to investigate the association between hyperuricemia and physical performance over a 4.4-year followup in the elderly. METHODS: A total of 1,904 community-dwelling older participants were followed for a mean of 4.4 years. Hyperuricemia at baseline was defined using serum uric acid concentrations ≥6 and ≥7 mg/dl for women and men, respectively. Objective physical performance tests measured included the Short Physical Performance Battery (SPPB), 4-meter gait speed, chair-stands time, leg extension and flexion, handgrip strength, and the 6-minute walking test. RESULTS: At baseline, participants with hyperuricemia (n = 98 men, 232 women) scored significantly worse in all the tests investigated. After adjusting for 19 covariates, men with hyperuricemia at baseline had an increased risk of having poor SPPB scores at followup (odds ratio [OR] 1.44 [95% confidence interval (95% CI) 1.21-1.72]; P < 0.0001), poor chair-stands time (OR 1.40 [95% CI 1.18-1.6]; P < 0.0001), poor leg extension (OR 1.47 [95% CI 1.21-1.7]; P < 0.0001), and poor handgrip strength (OR 1.54 [95% CI 1.24-1.90]; P < 0.0001). Among women, hyperuricemia was associated with an increased risk of having poor scores in all the SPPB items and in leg flexion (OR 1.26 [95% CI 1.08-1.49]; P = 0.03). CONCLUSION: Hyperuricemia seems to be significantly associated with poor physical performance in older people, over a followup of 4.4 years. The relationship appears to be more consistent in men than in women. Further longitudinal research is required to better understand the relationships and potential biologic pathways.

Factors Influencing Transitions Between Frailty States in Elderly Adults: The Progetto Veneto Anziani Longitudinal Study.

OBJECTIVES: To investigate frailty state transitions in a cohort of older Italian adults to identify factors exacerbating or improving frailty conditions. DESIGN: Population-based longitudinal study with mean follow-up of 4.4 years. SETTING: Community. PARTICIPANTS: Individuals enrolled in the Progetto Veneto Anziani (Pro.V.A.) (N = 2,925; n = 1,179 male, n = 1,746 female; mean age 74.4 ± 7.3). MEASUREMENTS: Frailty was identified at baseline and follow-up based on the presence of at least three Fried criteria; prefrailty was defined as the presence of one or two Fried criteria. Anthropometric, socioeconomic, and clinical characteristics were assessed at baseline in a personal interview and clinical examination using validated scales and medical history. RESULTS: During the study period, 1,114 (38.1%) subjects retained their baseline frailty status, 1,066 (36.4%) had a transition in frailty status, and the remainder of the sample died. Older age, female sex, obesity, cardiovascular disease, osteoarthritis, smoking, loss of vision, low levels of self-sufficiency and physical performance, cognitive impairment, hypovitaminosis D, hyperuricemia, and polypharmacy were associated with increasing frailty and greater mortality. Conversely, overweight, low to moderate drinking, high educational level, and living alone were associated with decreasing frailty. CONCLUSIONS: Frailty was confirmed as a dynamic syndrome, with socioeconomic and clinical factors that could be targets of preventive actions influencing transitions to better or worse frailty status.

Serum Thyroid-Stimulating Hormone Levels and Frailty in the Elderly: The Progetto Veneto Anziani Study.

High or low thyroid-stimulating hormone (TSH) levels seem to be associated with several negative outcomes in the elderly, but the literature about TSH and frailty is still limited. In this article, we investigated whether TSH is associated with prevalent and incident frailty in a cohort of older community-dwelling subjects. Among 3099 initially screened in the Progetto Veneto Anziani Study, 2571 men and women aged ≥65 years (for cross-sectional analyses) and 1732 (longitudinal, mean follow-up period of 4.4 years) were divided into sex-specific quintiles according to baseline serum TSH concentrations within normal range (0.3 and 4.2 mUI/L). Frailty was defined as the presence of three among five Fried's criteria. At baseline, taking those in the third quintile of serum TSH as reference (Q3) and adjusting for potential confounders, participants in the highest (Q5) quintile had an increased odds ratio (OR) of having frailty (OR = 1.55; 95% confidence interval [CI]: 1.03-2.33 for men; OR = 1.97; 95% CI: 1.59-2.45 for women). Men in Q1 had significant higher odds of having muscle weakness and exhaustion, while those in Q5 had muscle weakness and slow gait speed. Women in Q1 had significantly higher odds of having all the Fried's criteria (except for exhaustion), while those in Q5 reported a significantly higher presence of muscle weakness and slow gait speed. At follow-up, men in Q5 had an increased risk of frailty (OR = 1.37; 95% CI: 1.02-1.91) similar to women in Q1 (OR = 1.47; 95% CI: 1.21-1.78). In conclusion, men with higher and women with lower serum TSH levels are at increased risk of frailty.

Hyperuricemia, Cardiovascular Profile, and Comorbidity in Older Men and Women: The Pro.V.A. Study.

Hyperuricemia (HU) is growing worldwide and associates with several medical conditions in the elderly. However, data about older people and possible gender differences are sparse. The aim of this study was to compare HU prevalence rates and association with relevant medical disorders in elderly subjects of both sexes. Pro.V.A. is a survey of 3099 individuals aged 65+, focusing on chronic diseases and disability. Uric acid (UA) levels were dichotomized using 6.0 mg/dL (females) and 7.0 mg/dL (males), and multivariate logistic regression models were used to estimate odds ratios (ORs) between HU and single comorbidity. HU prevalence was 21.5% in females and 15.8% in males. HU was associated with most anthropometric and laboratory variables in women, but not in men. After adjustment for age, body mass index, and renal function, HU was independently associated with the presence of cardiovascular diseases in both sexes. In women, HU was associated with hand osteoarthritis (OR = 1.52; 95%CI: 1.12-2.08) and edentulism (OR = 1.31; 95%CI: 1.01-1.71), while resulted protective for osteoporosis (OR = 0.69; 95%CI: 0.53-0.91). In men, HU was significantly related with knee osteoarthritis (OR = 1.72; 95%CI: 1.06-2.79) and chronic obstructive pulmonary disease (OR = 1.60; 95%CI: 1.04-2.45). The presence of ≥4 comorbidities was a stronger determinant of HU in men (OR = 2.54; 95%CI: 1.21-5.37) than in women (ns). Patterns of age-dependent UA increase are markedly different in men and women. HU prevalence is substantial and its association with other diseases is gender specific, connoting a peculiar clinical profile.

A Comparison of Objective Physical Performance Tests and Future Mortality in the Elderly People.

Background: Physical performance is an important predictor of mortality, but little is known on the comparative prognostic utility of different objective physical performance tests in community-dwelling older adults. We compared the prognostic usefulness of several objective physical performance tests on mortality, adjusting our analyses for potential confounders. Methods: Among 3,099 older community-dwelling participants included in the Progetto Veneto Anziani study, 2,096 were followed for a mean of 4.4 years. Physical performance tests measured were Short Physical Performance Battery (SPPB), 4-meter gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), treated as continuous variables and categorized in gender-specific quartiles. The main outcome was mortality assessed with death certificates. Results: Participants who died during the follow-up (n = 327) scored significantly worse in all physical performance tests measured at baseline than those who survived (n = 1,769). Using a Harrell's C-index, the highest C-index was observed for 6MWT in men (C-index = 0.735; 95% confidence interval [CI]: 0.701-0.770, p < .0001) and SPPB in women (C-index = 0.781; 95% CI: 0.740-0.822, p = .0009). However, in both genders, only SPPB, 4-meter walking speed, and 6MWT are significant predictors of mortality. Analyses using sex-specific quartiles substantially confirmed these findings. Conclusions: Slow gait speed, 6MWT, and SPPB are significant predictors for mortality in community-dwelling older men and women. Physicians should consider using these tests to identify elderly individuals who are at higher risk of death to improve clinical decision making.