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Familial chylomicronemia syndrome (FCS) is a rare and severe genetic disorder, characterized by marked elevation of plasma triglycerides, often diagnosed in infancy. We describe the long-term follow-up (almost 60 years), the diagnostic assessment and the management of two siblings with severe hypertriglyceridemia and a history of pancreatitis who also developed cardiovascular complications later in life. We recently disclosed that the surviving index case was homozygous for a pathogenic LPL gene variant (c.984 GT, p.M328I). The same variant was also found in two apparently unrelated siblings with FCS living in the same geographical area as the index case.

Two hundred and fifty years have passed since the birth of Ludwig van Beethoven, and the enigma about his hearing loss and overall health status seems to be not completely solved. However, the admission to the hospital of a 64-year-old woman in 2018 with symptoms extremely similar to those experienced by the great composer may add further evidence to a theory previously underestimated. The health issues of the modern patient were found to be due to chronic lead intoxication. The lead was released during daily cooking using a ceramic-coated frying pan with worn surface that poisoned her breakfast most probably for years. Abdominal pain, asthenia, and hearing loss affecting the high frequencies with a many impact on speech intelligibility tormented the patient, as they had Beethoven. An extensive review of the music and medical literature was performed, as well as re-examination of manuscripts, correspondence, and autopsy reports of the famous composer; and great similarities have been found. The soundness of the most-cited classical theories about Beethoven's hearing loss will be discussed. After close scrutiny of the theories, our analysis points toward a progressive sensorineural hearing loss due to lead intoxication as the most probable cause of not only Beethoven's hypoacusis but his overall health status as well. Laryngoscope, 131:179-185, 2021.

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 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.

Aims To review the formation, catabolism, and the possible atherogenic properties of Lp-X. Data Synthesis The conversion of cholesterol to bile acids is regulated by several mechanisms including cholesterol 7 alpha hydroxylase, fibroblast growth factor 19, and farnesoid X receptors. During cholestasis these mechanisms are altered and there is an accumulation of bile acids and cholesterol in plasma. The hypercholesterolemia observed in cholestasis is due to the presence of an anomalous lipoprotein called lipoprotein-X (Lp-X). Lp-X is a lipoprotein rich in phospholipid and free cholesterol present in plasma of patients with cholestasis and, with some variations, in patients with lecithin-cholesterol-acyl-transferase deficiency (LCAT), and after lipid infusion. Lp-X is formed from a bile lipoprotein moving to the blood vessels where it incorporates small quantities of triglycerides, apo-C and esterified cholesterol and becomes a “mature” Lp-X. The activity of the phosphatidilcholine canalicular transporter Mdr2 P-glycoprotein (homologous to the human ABCB4) is essential for LpX appearance, since its suppression abolishes Lp-X formation. However, the concentration of Lp-X in plasma is determined also by the degree of the cholestasis, the residual liver function, and the LCAT deficiency. The Lp-X catabolism seems to be mediated by the reticuloendothelial system and possibly the kidney. Conclusions Lp-X might be considered a defense mechanism against the toxic effect of free cholesterol in cholestasis. The frequency of cardiovascular events in patients affected by primary biliary cholangitis, in whom the Lp-X is present in high concentration, are not increased. Further studies could now clarify the remaining open questions on the role of Lp-X in the dyslipidemia of cholestasis.

The mechanisms linking diabetes and cognitive impairment/dementia, two common conditions of elderly people, are not completely known. Brain-derived neurotrophic factor (BDNF) has antidiabetic properties, and reduced circulating BDNF was associated with dementia. We investigated the relationship between plasma BDNF levels, dementia, and diabetes in a sample of 164 community-dwelling elderly individuals, including 50 participants with vascular dementia, 44 with late onset Alzheimer's disease, 23 with cerebrovascular disease not dementia, and 47 controls (C). Presence/absence of diabetes was registered; new diagnoses of diabetes were made by the American Diabetes Association criteria. BDNF plasma levels were measured by ELISA. Both diagnosis of dementia and diabetes were associated with lower BDNF plasma values compared with the respective controls; moreover, dementia and diabetes correlated with BDNF plasma levels, independent of possible confounders. A progressive reductions of BDNF plasma levels from C (383.9 ± 204.6 pg/mL), to cerebrovascular disease not dementia (377.1 ± 130.2), to vascular dementia (313.3 ± 114.8), to late onset Alzheimer's disease (264.7 ± 147.7) was observed, (late onset Alzheimer's disease vs C, p: .03; late onset Alzheimer's disease vs cerebrovascular disease not dementia, p: .002). Demented patients affected by diabetes had the lowest BDNF mean levels (264.9 pg/mL) among individuals enrolled in this sample, suggesting the existence of a "synergistic" effect of dementia and diabetes on BDNF levels.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits biological activity on vascular cells in vitro. Rapid variation of circulating TRAIL levels occurs during acute coronary ischemia, suggesting that biological pathways involving TRAIL may be activated during ischemic heart disease. However, whether differential levels of soluble TRAIL in normal individuals are associated with adverse health outcomes has not been investigated. We tested the hypothesis that TRAIL levels predict mortality in a population based sample of community dwelling men and women.Plasma TRAIL level was measured by ELISA at baseline in 1282 adults (mean age 68 years) enrolled in the InCHIANTI study. Vital status was ascertained over the six-year follow-up.In multivariable Cox regression analysis adjusted for potential confounders including prevalent cardiovascular diseases (CVD), ankle-brachial index, electrocardiogram abnormalities, and inflammatory markers, baseline TRAIL levels were inversely related to all-cause mortality (p=0.008). In stratified analyses, the prognostic effect of TRAIL level was strong and highly significant in participants with prevalent CVD (N=321), (lowest versus highest quartile: HR 3.1; 95% CI 1.5-6.5) while it was negligible in those free of CVD (p value for the interaction term between CVD status and TRAIL levels=0.038). Similar findings were obtained when CVD mortality was considered as the outcome of interest.In older patients with CVD, low levels of TRAIL were associated with increased risk of death over a period of 6 years. Lower concentration of circulating TRAIL may be related to the clinical evolution of older adults with CVD.

Increased interleukin-6 plasma levels have been reported in metabolic syndrome (MS); nevertheless, it is unclear whether interleukin-6 activity is exerted through direct signalling only or also through the "trans-signalling". This issue is important to clarify since signalling and "trans-signalling" affect different tissues. We investigated the relationship between MS and the interleukin-6 system in an older population.Data from 997 older community dwelling individuals (age ≥ 65 years; females: 56.2%) enrolled the InChianti study were analysed. Interleukin-6, soluble interleukin-6 receptor (sIL-6r), and soluble glycoprotein 130 (sgp130) were measured on plasma by ELISA. MS was defined by the NCEP ATP III criteria; 309 individuals (31%) resulted affected by MS.Subjects with MS had higher interleukin-6 and sgp130 levels compared to controls; a trend toward higher levels of sIL-6R was also observed. The risk of having MS was increased in individuals with high sIL-6r or/and sgp130 levels, independent of age, gender, and interleukin-6 levels. Elevated sgp130 levels were associated with higher plasma glucose, HOMA, triglycerides, and with diabetes both in subjects with and without MS. Although the risk of high sgp130 levels was generally associated with MS (O.R.: 1.77, 95%C.I.: 1.39-2.25), this excess of risk was not present in MS phenotypes excluding the criteria "elevated glucose" or "elevated triglycerides". Furthermore, the association between sgp130 and MS disappeared after adjustment for HOMA.We found that older individuals with MS have increased sgp130 plasma levels compared with controls; nevertheless, our data suggest that this association might be mediated by insulin resistance.

DEMENTIA is a common disease in older individuals living in western societies. In the past years, numerous studies have suggested the existence of a relationship between lipids metabolism and dementia. However, studies that explored the relationship between plasma lipids and dementia have reported conflicting findings. Some (1,2) but not all (3,4) epidemiological studies suggested that elevated total cholesterol (TC) levels in the middle age might be a risk factor for dementia in late life. On the contrary, cross-sectional studies have consistently reported an association between low TC levels and the diagnosis of dementia in the elderly subjects (5–8). High TC levels in late life have been associated with a decreased risk of dementia (9–11); consistently decreasing levels of TC have been associated with dementia in older individuals (12–14). Only a few studies have evaluated the association between dementia and specific lipoprotein fractions, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C. This is an important issue since apo B–containing lipoproteins (LDL-C or non-HDL-C) and apo A–containing lipoproteins (HDL-C) have “opposite” functions in human physiology and have been associated with a pro- and antiatherogenic profile, respectively. Increased levels of LDL-C have been associated with Alzheimer’s disease (AD; 15,16), as well as dementia with stroke (17), but other studies failed to confirm these associations (8,18). On the contrary, some evidence suggests that low levels of HDL-C or Apo A-I might be associated with dementia in older individuals (19,20), and in particular with vascular dementia (21,22). Accordingly, high HDL-C values appeared to be protective against dementia in some (23) although not all studies (24,25). In the present study, we evaluated the association of different plasma lipid fractions with the prevalence of dementia in a large sample of Italian community-dwelling older individuals.

OBJECTIVES: To investigate the prospective relationship between alcohol consumption and incident mobility limitation. DESIGN: Cohort study. SETTING: The Health Aging and Body Composition study, conducted in Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Three thousand sixty-one adults aged 70 to 79 without mobility disability at baseline. MEASUREMENTS: Incidence of mobility limitation, defined as self-report at two consecutive semiannual interviews of any difficulty walking one-quarter of a mile or climbing stairs, and incidence of mobility disability, defined as severe difficulty or inability to perform these tasks at two consecutive reports. Alcohol intake, lifestyle-related variables, diseases, and health status indicators were assessed at baseline. RESULTS: During a follow-up time of 6.5 years, participants consuming moderate levels of alcohol had the lowest incidence of mobility limitation (total: 6.4 per 100 person-years (person-years); men: 6.4 per 100 person-years; women: 7.3 per 100 person-years) and mobility disability (total: 2.7 per 100 person-years; men: 2.5 per 100 person-years; women: 2.9 per 100 person-years). Adjusting for demographic characteristics, moderate alcohol intake was associated with lower risk of mobility limitation (hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.55–0.89) and mobility disability (HR=0.66, 95% CI=0.45–0.95) than never or occasional consumption. Additional adjustment for lifestyle-related variables substantially reduced the strength of the associations (HR=0.85, 95% CI=0.66–1.08 and HR=0.81, 95% CI=0.56–1.18, respectively). Adjustment for diseases and health status indicators did not affect the strength of the associations, suggesting that lifestyle is most important in confounding this relationship. CONCLUSION: Lifestyle-related characteristics mainly accounted for the association between moderate alcohol intake and lower risk of functional decline over time. These findings do not support a direct causal effect of alcohol intake on physical function.

Aims/Hypothesis: Idiopathic sudden sensorineural hearing loss (ISSNHL) represents an acute inner ear disorder with an overall incidence of 5–20/100000 individuals per year in western countries. No clear causes for this disease have been found so far, but cochlear ischemia has been hypothesized as one of the etiopathological mechanisms. The aim of our study was to assess the role of diabetes and traditional cardiovascular risk factors in the pathogenesis of ISSNHL. Materials/Methods: Case-control study of 141 patients (75 males/66 females) matched for age and gender. Cases were affected by ISSNHL, defined as a sudden hearing loss ≧30 dB, within 3 frequencies, developing over 72 h. The control group was composed of 271 sex- and age-matched subjects (142 males/129 females) who agreed to participate in this observational study and provided blood samples for laboratory investigations. Cardiovascular risk factors examined were: diabetes mellitus, smoking history, hypercholesterolemia, hypertriglyceridemia and hypertension. Results: On the univariate analysis, diabetes prevalence was higher in the ISSNHL group (15.6%) compared to controls (8.5%) (p = 0.03). Also hypercholesterolemia was significantly more frequent in the ISSNHL group compared to the control population. There were no statistically significant differences between the 2 populations concerning other cardiovascular risk factors. The risk of ISSNHL tended to increase as the number of cardiovascular risk factors increased (p for linear trend = 0.018). Conclusions: Our findings suggest that diabetes mellitus, hypercholesterolemia and a high burden of cardiovascular risk factors are associated with the risk of ISSNHL.

Metabolic syndrome (MS) and "low grade" systemic inflammation (LGSI) are very common findings in the older population. Although MS and LGSI have been associated in adults, it is not known what is the real contribution of MS, and its single components, to LGSI in older persons, due to the potential confounding effect of comorbidity and aging. We investigated the relationship between increased C-reactive protein (CRP) plasma levels, a marker of LGSI, and MS in 1044 older (> or =65 years) community dwelling Italian individuals enrolled the InChianti study. Metabolic syndrome was defined by the NCEP-ATP III-AHA/NHLBI criteria. High sensitivity CRP (hs.CRP) levels were measured by enzyme-linked immunosorbent assay, and defined as high when >3mg/L. The overall prevalence of MS was 31%. The prevalence of high hs.CRP was 54.5% in subjects with, and 41.3% in those without MS (p

Summary. Background: No experimental study has investigated the effect of whole-diet therapies on a wide range of hemostatic parameters, and their relationship with metabolic and inflammatory markers. Such information was sought in middle-aged women with moderate cardiovascular disease (CVD) risk subjected to an integrated healthy diet. Methods: Forty-nine premenopausal women were screened for C-reactive protein levels ≥1 mg L−1 and at least one additional CVD risk factor. Sixteen women (age: 43–54 years) were selected and received a 12-week diet (four phases) integrating National Cholesterol Education Program-Adult Treatment Panel-III recommendations with components of a Mediterranean-style diet. Results: We observed a reduction in body mass index (BMI) (P = 0.001), waist circumference (P = 0.005), total (P = 0.011) and low-density lipoprotein (LDL) cholesterol levels (P = 0.035). Antigen levels of coagulation factor (F)VII (P = 0.003) and FVIII (P = 0.005) were clearly reduced by dietary intervention, which also appeared to decrease circulating tissue factor but not fibrinogen and von Willebrand factor (VWF) antigen levels. Levels of FVIII and tumor necrosis factor-α, among the inflammation markers, showed the highest correlation, particularly before the intervention (r = 0.55, P = 0.032). Only this cytokine influenced FVIII variation over time, thus highlighting new relations between coagulation and cellular components of inflammation. The functional effect of diet on coagulation was indicated by markedly prolonged thrombin generation initiation and propagation times (lag time, P = 0.002; time to peak, P = 0.005). Conclusions: The changes observed in coagulation initiation and amplification phases, body composition and lipid profile could translate into a remarkable decrease in the risk for cardiovascular disease. Our observations suggest novel relationships between coagulation and inflammatory components.

Background. Functional evaluation is a cornerstone of multidimensional geriatric assessment; however, little is known of the clinical value of standardized performance-based assessment in the acute care setting. The aim of this study was to evaluate the clinical correlates and short-term predictive value of the Short Physical Performance Battery (SPPB) in older patients admitted to the hospital for an acute medical event. Methods. We enrolled 92 women and men 65 years old or older who were able to walk, who had a Mini-Mental State Examination (MMSE) score � 18, and who were admitted to the hospital with a clinical diagnosis of congestive heart failure, pneumonia, chronic obstructive pulmonary disease (COPD), or minor stroke. The SPPB was assessed at hospital admission and discharge. Self-report functional assessment included basic activities of daily living (ADL) and instrumental activities of daily living (IADL). Spearman’s rank correlation coefficients and multivariable linear regression analyses were used to study the association of SPPB score and functional and clinical characteristics, including length of hospital stay. Results. The mean age was 77.7 years (range 65–94 years), 49% were female, 64.1% had congestive heart failure, 16% COPD, 13.1% pneumonia, and 6.5% minor stroke. At hospital admission the mean SPPB score was 6.0 6 2.7. SPPB scores were inversely correlated with age, the severity of the index disease, and IADL and ADL difficulty 2 weeks before hospital admission (p , .01), and were directly correlated with MMSE score (p ¼ .002). On average, SPPB score increased 1 point (þ0.97, standard error of the mean ¼ 0.2; p for paired t test , .001) from baseline to hospital discharge assessment. After adjustment for potential confounders, baseline SPPB score was significantly associated with the length of hospital stay (p , .007). Conclusion. In older acute care inpatients, SPPB is a valid indicator of functional and clinical status. SPPB score at hospital admission is an independent predictor of the length of hospital stay.

A low level of high-density lipoprotein cholesterol (HDL-C) is an important risk factor for atherosclerosis and its clinical complications.1 The importance of HDL as a risk factor for cardiovascular disease and mortality has been further emphasized in the older population, where HDL-C level may have better predictive value than other lipid risk factors.2,3 More recently, the prognostic value of HDL-C levels has been expanded to other common conditions of older people, suggesting that HDL-C may have further clinical relevance in addition to the inverse relationship with atherosclerosis.4 For example, low HDL-C combined with low serum albumin identified older persons with the highest risk of all-cause and noncardiovascular mortality.5 Low HDL-C has been correlated with cognitive impairment and dementia, and at least part of the association might be independent of atherosclerotic disease.6 Furthermore, there is initial evidence that values of HDL-C are inversely correlated with physical disability and motor performance.7 The ability to remain mobile is an essential aspect of quality of life and is critical for the preservation of independence in old age. Objective measures of lower extremity function, including walking speed and muscle strength, are strong predictors of severe disability, hospitalization, institutionalization, and death.8–11 Causes of impaired mobility and lower extremity function that are potentially modifiable include a number of sociodemographic and behavioral characteristics, acute and chronic diseases,12 and several metabolic conditions, including obesity, diabetes mellitus and insulin resistance, a chronic low-grade inflammatory state,13 and a high level of oxidative stress.14 HDL-C is inversely correlated with most of the above-mentioned conditions, and recent studies have reported an antiinflammatory and antioxidant effect of Apolipoprotein A-I–containing lipoproteins,15 suggesting that, through these biological activities, HDL-C may counteract the disablement process in older persons.16 The aim of this study was therefore to evaluate the independent association between HDL-C levels and different objective measures of lower extremity performance in a sample of community-dwelling nondisabled older persons. It was hypothesized that subjects with higher HDL-C levels would have better physical performance, and the study sought to assess the direct and indirect contribution of several clinical and biochemical characteristics correlated with HDL-C levels in explaining the relationship between HDL-C and physical performance.

The most frequent form of monogenic hypercholesterolemia, also known as Familial Hypercholesterolemia (FH), is characterized by plasma accumulation of cholesterol transported in Low Density Lipoproteins (LDLs). FH has a co-dominant transmission with a gene-dosage effect. FH heterozygotes have levels of plasma LDL-cholesterol (LDL-C) twice normal and present xanthomas and coronary heart disease (CHD) in adulthood. In rare FH homozygotes plasma LDL-C level is four times normal, while xanthomas and CHD are present from infancy. Most FH patients are carriers of mutations of the LDL receptor (LDLR); a minority of them carry either mutations in the Apolipoprotein B (ApoB), the protein constituent of LDLs which is the ligand for LDLR, or gain of function mutations of PCSK9, the protein responsible for the intracellular degradation of the LDLR. From 1970 to the mid 90s some publications described children with the clinical features of homozygous FH, who were born from normocholesterolemic parents, strongly suggesting a recessive transmission of FH. In these patients the involvement of LDLR and APOB genes was excluded. Interestingly, several patients were identified in the island of Sardinia (Italy), whose population has a peculiar genetic background due to geographical isolation. In this review, starting from the early descriptions of patients with putative recessive hypercholesterolemia, we highlight the milestones that led to the identification of a novel gene involved in LDL metabolism and the characterization of its encoded protein. The latter turned out to be an adaptor protein required for the LDLR-mediated endocytosis of LDLs in hepatocytes. The loss of function of this protein is the cause of Autosomal Recessive Hypercholesterolemia (ARH).

Background. The association between total serum cholesterol and health outcomes among older adults is controversial. The objective of the present study was to determine within a cohort of acutely hospitalized disabled elderly patients whether total cholesterol predicts recovery from disability in basic activities of daily living (ADL). Methods. Patients (3150) 65 years old or older admitted to 81 acute care units in Italy and presenting with ADL disability at hospital admission were included in this study. ADL disability was defined as need of assistance or total dependence in one or more ADLs (eating, dressing, personal hygiene, transferring, and toilet use). Recovery was defined as no disability at hospital discharge in any of the five ADLs considered. Results. Mean age of study participants was 80.5 6 7.2 years, and 1305 (41.1%) were men. The rate of recovery from ADL disability was 14.5% for participants with total cholesterol ,200 mg/dL (n ¼ 306/2108), 20.2% for those with total cholesterol between 200 and 239 mg/dL (n ¼ 144/713), and 23.1% for those with total cholesterol � 240 mg/dL (n ¼ 76/ 329). After adjustment for potential confounders, relative to that of patients with cholesterol ,200 mg/dL, risk ratios for recovery were 1.31 for participants with cholesterol between 200 and 239 mg/dL (95% confidence interval [CI], 1.07– 1.62) and 1.36 (95% CI, 1.04–1.79) for those with cholesterol � 240 mg/dL. After exclusion of 769 patients with total cholesterol ,145 mg/dL, the risk ratios (compared with those for participants with cholesterol ,200 mg/dL) for recovery were 1.33 (95% CI, 1.07–1.66) for participants with cholesterol between 200 and 239 mg/dL and 1.41 (95% CI, 1.06– 1.88) for patients with cholesterol � 240 mg/dL. Conclusions. Among hospitalized disabled older adults, elevated levels of cholesterol are associated with increased rate of recovery from ADL disability.

OBJECTIVES: To evaluate the predictive value of hemoglobin levels upon hospital admission on recovery from activity of daily living (ADL) disability during hospital stay in older patients. DESIGN: Longitudinal observational study. SETTING: Geriatric and internal medicine acute care units. PARTICIPANTS: Data are from 5,675 patients aged 65 and older enrolled in the Italian Group of Pharmacoepidemiology in the Elderly Study with ADL disability upon hospital admission. MEASUREMENTS: ADL disability was defined as inability to perform or need for assistance in performing one or more ADLs. Recovery from ADL disability was defined as independence in ADLs upon hospital discharge. Anemia was defined according to the World Health Organization criteria. Sociodemographic and clinical characteristics were considered as potential confounders. RESULTS: Mean age was 80.5 years; 57.7% of subjects were female. Prevalence of anemia was 46.8%. A total of 536 (9.4%) participants regained independence in all six ADLs at hospital discharge. Patients with anemia had a lower rate of recovery from ADL disability than those with normal hemoglobin levels (7.0% vs 11.6%; P

Objectives: To study the association between performance on psychological tests of executive function and performance on lower extremity tasks with different attentional demands in a large sample of nondemented, older adults. Design: Cross-sectional study. Setting: Community-based. Participants: Nine hundred twenty-six persons aged 65 and older, without dementia, stroke, parkinsonism, visual impairment, or current treatment with neuroleptics, enrolled in a large epidemiological study. Measurements: Trail Making Test (TMT) parts A and B and two performance-based measures of lower extremity function that require different executive/attentional-demanding skills: walking speed on a 4-m course at usual pace and walking speed on a 7-m obstacle course at fast pace. A difference score (Delta TMT), obtained by subtracting time to perform part A from time to perform part B of the TMT, was used as an indicator of executive function. Based on Delta TMT, subjects were divided into poor performance, intermediate performance, and good performance. Results: After adjustment, no association between Delta TMT and 4-m course usual-pace walking speed was found. Participants with poor Delta TMT and with intermediate Delta TMT performance were more likely to be in the lowest tertile for 7-m obstacle course walking speed. Conclusion: In nondemented older persons, executive function is independently associated with tasks of lower extremity function that require high attentional demand.

Summary Background and aim Elevation of plasma cholesterol and/or triglycerides, and the prevalence of small dense low density lipoproteins (LDL) particles remarkably increase the risk in patients with familial combined hyperlipidemia (FCHL). There are, at present, inconsistent data on the effects of different treatments on size and density of LDL particles in FCHL patients. Methods and results A multicenter, randomized, double-blind, double-dummy, parallel group study was designed to evaluate the effect of 3 months' treatment with atorvastatin (10 mg/day) or pravastatin (20 mg/day) on the lipid/lipoprotein profile and LDL size in a total of 86 FCHL patients. Both statins significantly lowered plasma total and LDL cholesterol, with a significantly higher hypocholesterolemic effect observed with atorvastatin (−26.8 ± 11.1% and −35.9 ± 11.1%, respectively) compared to pravastatin (−17.6 ± 11.1% and −24.5 ± 10.2%). The percent decrease in plasma triglycerides was highly variable, but more pronounced with atorvastatin (−19.8 ± 29.2%) than with pravastatin (−5.3 ± 48.6%). Opposite changes in LDL size were seen with the 2 treatments, with increased mean LDL particle diameter with atorvastatin, and decreased diameter with pravastatin, and significant between treatment difference in terms of percent modification vs baseline (+0.5 ± 1.6% with atorvastatin vs −0.3 ± 1.8% with pravastatin). Conclusions The present results support the evidence indicative of a greater hypocholesterolemic effect of atorvastatin compared to pravastatin, and in addition show a raising effect of atorvastatin on the size of LDL particles in FCHL patients.

Background and aims: The aim of this study was to verify the hypothesis that a combined measurement of albumin and HDL-C might predict total mortality in institutionalized frail older residents. Methods: Participants were 344 older subjects (272 F, 72 M), living in the “Istituto Riposo Anziani” (I.R.A.), a nursing-home located in Padova, North-east Italy. Functional status, comorbidity, and clinical chemistry parameters were evaluated at entry. All-cause mortality was evaluated after 2 and 4 years. The sample was divided into 4 groups by using the 50° percentile of albumin and HDL-C as cut-off value. The mortality odds ratio (OR) was estimated by multivariate logistic regression analysis. Results: Total mortality was 36.8% after 2 years and 51.8% after four years. A trend toward an increase in mortality from group 1 to 4 was observed (p for trend: 0.01). The OR for 2 and 4 years mortality was 3.83 (95% CI 1.86–7.58) and 2.66 (95% CI 1.37–5.17), respectively, in group 4 compared with group 1, after adjustment for age, gender, number of chronic diseases, functional status, BMI, diabetes, dementia, stroke, CHD, CHF, hypertension, depression, COPD, and total cholesterol levels. Conclusions: Among frail older nursing-home residents, simple measurement of serum albumin and HDL-C levels may be useful in identifying varying degrees of frailty.

Objectives: To investigate the relationship between body composition (assessed using body mass index (BMI) and body cell mass (BCM)) and all-cause mortality in a sample of older nursing home residents. Design: Prospective study with a median follow-up period of 3.5 years. Setting: Istituto di Riposo per Anziani, Padua, Italy. Participants: A total of 344 participants (79.1% women) aged 65 and older at baseline. Measurements: Anthropometric, nutritional, and metabolic parameters were measured at baseline. BCM was measured using tetrapolar bioelectric impedance analysis. Up to 4 years of follow-up data for vital status were available. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox proportional hazards models. Results: During the follow-up period, there were 179 deaths. After adjustment for age and sex, subjects with low BMI and low BCM (lowest sex-specific tertiles) had significantly higher mortality than those with higher BMI or BCM levels. In a fully adjusted regression model, there was no association between BMI levels and risk of mortality, with subjects in the top tertile having the same likelihood of mortality as subjects in the lowest tertile (relative risk (RR)=0.94, 95% confidence interval (CI)=0.61–1.43). Conversely, there was a strong and significant inverse association between BCM levels and mortality (RR for tertile III=0.55, 95% CI=0.35–0.87; P

Background and Purpose— Antithrombotic therapy has been demonstrated as an effective tool for secondary ischemic stroke prevention. Nevertheless, scant data are available on actual prescription of this therapy in clinical practice. Methods— A total of 17 337 patients admitted to geriatric and internal medicine wards participating in the study in the 1993 to 1998 survey period were analyzed. Patients with coded diagnoses of ischemic stroke and transient ischemic attack (TIA) were selected. Data recorded included demographic and clinical characteristics and medication prescription during hospital stay and at discharge. Logistic regression analyses were used to identify conditions associated with the prescription of antiplatelet or anticoagulant drugs. Results— Among 946 patients with diagnosis of stroke or TIA (mean age 78 years), >40% was discharged without antithrombotic prescription. Conditions that made the prescription more unlikely were diagnosis of stroke (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.44 to 0.86), presence of anemia (OR: 0.70; 95% CI: 0.49 to 0.98), severe disability (OR: 0.48; 95% CI: 0.30 to 0.75), and cognitive impairment (OR: 0.58; 95% CI: 0.43 to 0.75). There was an independent and additive association of physical and cognitive status with antithrombotic therapy prescription. Conclusions— A high rate of patients affected by stroke or TIA are discharged from the hospital without antithrombotic therapy. The most important correlates of the likelihood of not receiving an antithrombotic medication were cognitive and functional status.

Background— Increased levels of acute-phase reactants predict the onset of poor health outcomes. A U-shaped association has been reported between alcohol intake and health outcomes, which suggests that alcohol intake may modify levels of acute-phase reactants. We investigated the relationship between weekly alcohol intake and interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1). Methods and Results— Data are from year 1 of the Health, Aging, and Body Composition study, a biracial cohort of 3075 well-functioning men and women aged 70 to 79 years, living in Memphis, Tenn, and Pittsburgh, Pa. The analysis included 2574 persons (51.2% women; 40.1% black) with complete data. After adjustment for age, race, smoking status, history of diabetes, history of cardiovascular disease, physical activity, high-density lipoprotein cholesterol, antiinflammatory medications, statins, and total fat mass, alcohol intake showed a J-shaped relationship with mean IL-6 ( P for quadratic term P =0.014) levels. The association was consistent in both men and women. Compared with subjects who consumed 1 to 7 drinks per week, those who never drank had an increased likelihood of having high levels of both IL-6 and CRP, as did those who drank 8 or more drinks per week. We found no relationship between alcohol intake and levels of TNF-α and PAI-1 ( P =0.137 and 0.08, respectively). Conclusions— In well-functioning older persons, light alcohol consumption is associated with lower levels of IL-6 and CRP. These results might suggest an additional biological explanation to the epidemiological link between moderate alcohol consumption and cardiovascular events.

Background and objective: In Western countries, stroke is the third most common cause of death and one of the main causes of disability in individuals aged over 65 years. Mortality at 1 month after stroke is still high, at around 25–30%. Despite the widespread use of anti-oedema agents in clinical practice, there are only a few studies that have investigated the effect of these drugs on stroke outcome. In this study we evaluated the effect of intravenously administered glycerol or mannitol individually and in combination with corticosteroids, on short-term mortality (30 days). The sample included patients aged over 65 years who were admitted to hospital for acute ischaemic stroke. Study Design: This was a retrospective cohort study. The odds ratio, estimated by means of multivariate logistic regression method, was used to compare short-term mortality risk across treatment groups after adjusting for possible confounders. Methods: This study included 442 consecutive patients aged over 65 years with severe ischaemic stroke who were admitted to either the University School of Internal Medicine (Ferrara) or the Geriatric Department (Perugia), Italy, over a 4-year period (1996–2000). All patients underwent a computed tomography (CT) scan of the brain within 72 hours of admission. Stroke type was classified according to the system used by the Oxfordshire Community Stroke Project. The data recorded included: (i) clinical features of stroke; (ii) detailed medical history, including vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, coronary heart disease, congestive heart failure, alcohol abuse, smoking, previous transient ischaemic attacks or stroke); (iii) 12-lead ECG; and (iv) routine blood analysis and urine tests. Results: No reduction in short-term mortality risk was observed in patients treated with intravenous (IV) glycerol. However, an increase in short-term mortality risk was observed in the patients who were concurrently treated with IV corticosteroids. Similarly, treatment with mannitol did not reduce the risk of short-term mortality; however, concurrent treatment with IV corticosteroids did not show a significant rise in short-term mortality risk. When treatment with IV glycerol and mannitol was considered together, the treatment did not decrease short-term mortality risk, while concurrent therapy with corticosteroids was associated with an increase in short-term mortality risk. Conclusion: This study does not support the use of IV osmotic agents such as glycerol or mannitol in the prevention of short-term mortality in older patients with acute ischaemic stroke. Furthermore, our data suggest a possible harmful effect of IV corticosteroids on short-term mortality risk.

Passaro A, Calzoni F, Volpato S, Dalla Nora E, Pareschi PL, Zamboni PF, Fellin R, Solini A (University of Ferrara; Diabetes Division Arcispedale S. Anna, Ferrara; and University of Pisa, Italy). Effect of metabolic control on homocysteine levels in type 2 diabetic patients: a 3-year follow-up. J Intern Med 2003; 254: 264–271. Objectives. Hyperhomocysteinaemia has emerged as a novel risk factor for cardiovascular disease. The determinants of total homocysteine (tHcy) levels in type 2 diabetic patients (D2p) have not been studied in detail. We examined prospectively the effect of different degrees of metabolic control on plasma tHcy in D2p with preserved kidney function. Subjects and main outcome measurements. Ninety-five D2p were studied. Clinical parameters, fasting plasma glucose, HbA1c, serum lipids, blood urea nitrogen (BUN) and creatinine, vitamin B12 and folate and tHcy were measured at the baseline and after 36 months. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism was also determined. Subjects were categorized according to δHbA1c into group A (±1 point), B (>1 point increase) or C (>1 point decrease). Results. Total homocysteine was reduced in subjects whose HbA1c decreased with time, whilst patients showing a worsened metabolic control had an increased tHcy in respect to baseline. A larger response to the improved metabolic control in terms of tHcy reduction was noted in wild type patients versus those homozygous for the mutation. A multivariate analysis revealed MTHFR polymorphism and HbA1c as strong determinants of changes in tHcy with time. Conclusions. The findings suggest that in D2p tHcy decreases even with modest improvement of glycaemic control; moreover patients homozygous for the MTHFR C677T mutation show the largest changes in tHcy levels with concomitant changing of HbA1c. These results define a further mechanism through which hyperglycaemia might promote cardiovascular damage in diabetic patients.

Although total cholesterol levels among middle-aged persons correlate with long-term mortality from all causes, this association remains controversial in older persons. We explored whether total cholesterol levels were independently associated with in-hospital mortality among elderly patients.We analyzed data from a large collaborative observational study, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), which collected data on hospitalized patients. A total of 6984 patients aged 65 years or older who had been admitted to 81 participating medical centers during four survey periods (from 1993 to 1998) were enrolled. Patients were divided into four groups based on total cholesterol levels at hospital admission:160 mg/dL (n = 2115), 160 to 199 mg/dL (n = 2210), 200 to 239 mg/dL (n = 1719), andor=240 mg/dL (n = 940).Patients (mean [+/- SD] age, 78 +/- 7 years) were hospitalized for an average of 15 +/- 10 days. The mean total cholesterol level was 186 +/- 49 mg/dL. A total of 202 patients died during hospitalization. Mortality was inversely related to cholesterol levels (160 mg/dL: 5.2% [110/2115]; 160-199 mg/dL: 2.2% [49/2210]; 200-239 mg/dL: 1.6% [27/1719]; andor=240 mg/dL: 1.7% [16/940]; P for linear trend0.001). After adjustment for potential confounders (demographic characteristics, smoking, alcohol use, indicators of nutritional status, markers of frailty, and comorbid conditions), low cholesterol levels continued to be associated with in-hospital mortality. Compared with patients who had cholesterol levels160 mg/dL, the odds ratios for in-hospital mortality were 0.49 (95% confidence interval [CI]: 0.34 to 0.70) for participants with cholesterol levels of 160 to 199 mg/dL, 0.41 (95% CI: 0.26 to 0.65) for those with cholesterol levels of 200 to 239 mg/dL, and 0.56 (95% CI: 0.32 to 0.98) for those with cholesterol levelsor=240 mg/dL. These estimates were similar after further adjustment for inflammatory markers and after excluding patients with liver disease.Among older hospitalized adults, low serum cholesterol levels appear to be an independent predictor of short-term mortality.

In the last 10 years, new types of genetic hypercholesterolemia, different from familial hypercholesterolemia (FH) or familial defective apo B (FDB), have been reported; these forms have both autosomal dominant or recessive inheritance. Starting in 1995, we have described a new recessive type of hypercholesterolemia, named ARH. This disease, initially reported in one Sardinian family, is characterized by a severe increase of low-density lipoproteins (LDL) in plasma, xanthomas, xanthelasmas, and premature coronary heart disease. The family showed presence of consanguinity, bimodal distribution of cholesterol levels, and absence of vertical transmission. We have demonstrated that this hypercholesterolemia is due to a marked reduction of LDL catabolism that is caused by a selective reduction of LDLs uptake by the liver. The gene responsible for ARH maps to chromosome 1p35. It codes for an adaptor protein that interacts with the NPXY sequence in the cytoplasmic tail of LDL-R, and is necessary for the functioning of LDL-R in liver, but not in fibroblasts. Only two mutations were identified in Sardinia; a single base pair insertion in exon 4 (ARH1), and a nonsense mutation at codon 22 (ARH2). The high frequency of ARH in the island is probably due to a combination of genetic drift, consanguinity, and geographic isolation.

Familial predisposition together with several environmental factors may be involved in the pathogenesis of common prostate disease such as benign hypertrophy or prostate neoplasm. A higher incidence of both these conditions has been described in some insulin-resistant states such as obesity, but not much information is available on the effect of metabolic profile on gland morphology. The aim of this study was to evaluate the relation between glucose and lipid pattern and prostate diameters in two groups of non-diabetic individuals with benign prostate hypertrophy or cancer. 109 patients were recruited; plasma glucose, lipids and hormonal profile as well as an ultrasonographic evaluation of the gland volume and diameters were determined. Patients with prostate cancer had significantly higher levels of insulin and were more insulin resistant; in contrast, in subjects with prostate hypertrophy, fasting plasma glucose and--to a lesser extent--serum triglycerides emerged as the main determinants of gland volume. These observations may indicate that an improvement of insulin sensitivity and strategies to maintain a strict glucose and lipid control even in non-diabetic subjects are useful objectives in the prevention of prostate diseases.

OBJECTIVE—Older patients with diabetes are more likely to have a higher prevalence of multiple risk factors for physical disability, as a result of diabetic complications. We evaluated the pace of decline in lower-extremity function and the risk for progression of disability in older women with diabetes. RESEARCH DESIGN AND METHODS—We conducted a 3-year longitudinal cohort study of a random sample of 729 physically impaired older women (age ≥65 years) living in the community (Baltimore, MD). Diabetes was ascertained by standard criteria. Self-reported functional status and objective performance measures were assessed at baseline and over six semiannual follow-up visits. RESULTS—The baseline prevalence of diabetes was 14.4%. After adjustment for age and compared with women without diabetes, those with diabetes had an RR of 1.8 (95% CI 1.3–2.5) for incident mobility disability and 1.6 (1.2–2.1) for incident activity of daily living disability. The increased incidence of new disability associated with diabetes was paralleled by a greater decline in objective measures of lower-extremity function. Adjustment for multiple risk factors for disability did not significantly attenuate the risk for disability associated with diabetes. CONCLUSIONS—In older patients, impaired lower-extremity function is a long-term diabetic complication. Comprehensive assessment of older diabetic patients should include a standardized evaluation of lower-extremity performance.

Summary Background Autosomal recessive hypercholesterolaemia (ARH) is caused by mutations in a putative adaptor protein called ARH. This recessive disorder, characterised by severe hypercholesterolaemia, xanthomatosis, and premature coronary artery disease, is rare except on the island of Sardinia, Italy. Our aim was to ascertain why ARH is more common on Sardinia than elsewhere. Methods We obtained detailed medical histories, did physical examinations, measured concentrations of lipoproteins, and harvested genomic DNA from 28 Sardinians with ARH from 17 unrelated families. We sequenced the coding regions and consensus splice sites of ARH in probands from these families, and from 40 individuals of non-Sardinian origin who had an autosomal recessive form of hypercholesterolaemia of unknown cause. Findings Two ARH mutations, a frameshift mutation (c432insA) in exon 4 ( ARH1 ) and a nonsense mutation (c65G-A) in exon 1 ( ARH2 ), were present in all of the 17 unrelated families with ARH. Three of the ARH alleles contained both mutations, as a result of an ancient recombination between ARH1 and ARH2 . No regional clustering of the three mutant alleles within Sardinia was apparent. Furthermore, four Italians from the mainland with autosomal recessive hypercholesterolaemia were homozygous for ARH1 . Interpretation The small number, high frequency, and dispersed distribution of ARH mutations on Sardinia are consistent with these mutations being ancient and maintained in the Sardinian population because of geographic isolation.

It is with sincere regret and sadness that we announce the premature death of Prof. Andrea Mezzetti at the cruelly young age of 64 after a long battle against his disease, which he fought with remarkable stoicism. Andrea Mezzetti was an outstanding researcher, teacher, and mentor. He dedicated his scientific career to investigating several aspects of cardiovascular pathophysiology as well as of prevention and treatment of atherosclerosis. In the last three years he served as President of the Italian Society for the Study of Arteriosclerosis (SISA) to which he dedicated all his efforts and commitment. He continued his work until shortly before his death with a sense of purpose and tenacity and remained a champion of cardiovascular medicine both at home and abroad.

Background: The aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methods: We used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.Results: Of the 1380 patients enrolled, 27.9% had HF (age 80 ± 7, BMI 27 ± 6 kg/m2) and 17.4% CKD (age 81 ± 7, BMI 26.8 ± 6 kg/m2). Both groups were significantly older (P

Plasma homocysteine (Hcy) is an independent vascular risk factor. Its remethylation to methionine is regulated by the activity of the enzyme 5,10-methylene tetrahydrofolate reductase (MTHFR). A C-to-T substitution at nucleotide 677 of the MTHFR gene is frequently associated to hyperhomocysteinemia. In this study, we evaluated the relationship among MTHFR C677T polymorphism, Hcy and some ultrasonographic parameters at the level of carotid arteries in 120 elderly women with normal ECG, normal blood pressure values, total cholesterol

OBJECTIVES Paraoxonase, angiotensin-converting enzyme (ACE), methylenetetrahydrofolate reductase (MTHFR), and apo E gene polymorphisms were evaluated in older patients with vascular dementia (VD) or late-onset Alzheimer's disease (LOAD). MATERIAL AND METHODS Sixty patients with VD, 45 patients with LOAD, and 54 non-demented controls were compared. RESULTS No differences in the distribution of paraoxonase, ACE, and MTHFR polymorphisms were found. The overall frequency of apo E epsilon4 allele was "low"; epsilon4 allele was more frequent in LOAD (17.5%) and VD (13.3%) compared with controls (9.2%), but the difference was not statistically significant. CONCLUSION Paraoxonase, ACE, and MTHFR polymorphisms were not associated with VD or LOAD; these common polymorphisms might have a marginal role in the pathogenesis of dementia in older subjects. In spite of a "low" frequency of the apo E epsilon4 allele in our sample, the frequency of epsilon4 allele was about double in LOAD compared with controls.

Besides functional impairment, several factors have been associated with mortality in institutionalized older subjects, including advanced age, gender, comorbidity, and malnutrition. We investigated the possible association of a large number of factors, including functional, anthropometric, nutritional, metabolic, clinical, and demographic variables, with two-year all-cause mortality inasample of 344 institutionalized older subjects (65 years) without evidence of acute illness at the time of observation. Although a number of factors were associated with mortality risk, multivariate analysis showed that only severe disability (6 vs 0–1 lost ADL, O.R.: 3.37, C.I. 95%: 1.76–7.3) and low albumin levels (lowest vs highest tertile: O.R.: 3.0, C.I. 95%: 1.65–5.43) were independent predictors of outcome. Moreover, in the analysis stratified for degree of disability and albumin tertiles, we found a strong gradient in mortality risk with increasing disability and decreasing albumin levels. These results further support the value of these two simple parameters in identifying frail institutionalized older individuals.

In recent years, the use of benzodiazepines has been recognized as an independent risk factor for falls among the elderly. To evaluate the role of different types of benzodiazepines in determining falls in a hospitalized geriatric population, we conducted a prospective study among 7908 patients consecutively admitted in 58 clinical centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA), during an 8-month observation period (1991 and 1993). Over 70% of the patients were older than 65 years, 50% were women, and 23. 6% had a benzodiazepine prescription during hospital stay. The number of patients who experienced one or more falls during follow-up was 174 (2.2%). Sixty falls occurred among patients taking benzodiazepines (3.2%) and 114 (1.9%) among those who did not use benzodiazepines; the crude odds ratio for users versus non-users was 1.7 (95% CI 1.2-2.3). Multivariate logistic regression analysis showed that benzodiazepines with very short (OR 1.9; CI 1.03-3.3) and short half-life (OR 1.8; CI 1.2-2.8) were positively associated with falls during hospital stay. Patients who used other psychotropic agents (OR 2.3; CI 1.7-3.4), antidiabetic agents (OR 1. 5; CI 1.03-2.2), patients with presence of cognitive impairment (OR 1.6; CI 1.08-2.3), high level of comorbidity (OR 1.7; CI 1.05-2.9), more advanced age (>80 years, OR 2.7; CI 1.5-4.7) and those who stayed in the hospital for 17 days or more (OR 2.1; CI 1.4-3.3) were also at a greater risk. These findings suggest that benzodiazepines with short and very short half-life are an important and independent risk factor for falls and their prescription to elderly hospitalized patients should be carefully evaluated.

Aging is frequently associated with a deterioration in health and functional status, which often induces important modifications in several biological parameters, including plasma lipids; as a consequence, the real "meaning" of lipoprotein parameters in old individuals is complex. A cross sectional study was carried out in order to investigate the lipoprotein profile in very old individuals with or without disability, and evaluate the possible influence of other biological variables on plasma lipids. One hundred selected healthy free-living (FL) and 62 disabled (DIS) subjects aged over 80 were enrolled; 91 healthy adults matched for origin were included as controls. Lipoprotein profile [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apoprotein A-I and B], anthropometric parameters, and ADL were measured. The FL octo-nonagenarians featured higher HDL-cholesterol levels than adult controls. DIS octo-nonagenarians showed lower total and HDL-C levels than FL. Discriminant analysis indicated that HDL-cholesterol and apoprotein A-I, but not total cholesterol, strongly discriminated between FL and DIS octo-nonagenarians. Multivariate analysis demonstrated that the waist/hip ratio, an index of visceral adiposity, was negatively associated with HDL-C levels in FL, but not in DIS elderly. We conclude that: 1) in very old individuals, the absence or presence of disability is strongly associated with high or low HDL-cholesterol values, respectively; 2) HDL-C and apo A-I are the parameters which better discriminate between FL and DIS octo-nonagenarians; and 3) the differences in HDL-C levels between FL and DIS are not due to modifications in anthropometric parameters. Prospective studies are needed to better understand the relationship between high-density lipoprotein levels, disability and aging.

Peripheral atherosclerosis (carotid and aortofemoral vascular districts) shows some peculiar characteristics with respect to coronary atherosclerosis. In this paper we have reviewed the most recent studies on the relationships between atherosclerosis of the limbs and lipid metabolism. Several authors have described increased plasma levels of lipoprotein remnants, lipoprotein (a) and some lipid peroxidation parameters in extracoronary atherosclerosis, while HDL (and their subfractions) seem to be reduced. Some of these modifications may be related to the direct metabolic effects of smoking and diabetes, which frequently coexist. Recent intervention trials show a possible regression of established atherosclerotic plaques after hypolipidemic therapy. This further underscores the role of plasma lipoprotein pattern in determining peripheral vascular lesions.

OBJECTIVE: It has recently been proposed that increased oxidative stress may play a role in the aging process and age-associated degenerative diseases. DESIGN AND MEASUREMENTS: A cross-sectional study was carried out to assess the relationship of circulating antioxidants, namely vitamins E and C, β-carotene, proteic thiols (P-SH) and ceruloplasmin, and of lipid peroxides, with both aging and aging with disability, i.e., unsuccessful aging. PARTICIPANTS: One hundred healthy free living and 62 disabled octo-nonagenarians and 91 healthy adults were enrolled in the study. RESULTS: Free living and disabled older adults had lower antioxidant and higher lipid peroxide levels than healthy adults, as well as the disabled older adults compared with free living older persons. Using logistic regression, we observed that plasma concentrations of vitamins E and C, P-SH, and lipid peroxides were independently associated with either aging or aging with disability, apparently representing biochemical indicators of patient status. In particular, aging and unsuccessful aging were associated with higher levels of lipid peroxides independently of circulating levels of vitamins C and E, suggesting that the increased oxidative stress was not merely an effect of a lower dietary intake of antioxidants. Serum ceruloplasmin was significantly higher in free living older adults than in healthy adults, and in the disabled compared with free living octo-nonagenarians. CONCLUSIONS: Our findings are consistent with the presence of systemic oxidant load in older adults, and this phenomenon is far more evident in unsuccessful aging.

Cardiovascular diseases are the leading cause of disability and mortality in western countries. Lipoprotein(a) [Lp(a)] is now considered an independent risk factor for atherosclerosis, and might consequently be related to longevity and/or disability. In the context of a study on metabolic and anthropometric parameters in a sample of Italian octo- nonagenarians, Lp(a) and apo(a) isoforms were evaluated. One- hundred and fifty Italian octo- nonagenarians were classified as free- living or disabled, according to Katz’s index, and compared to 91 healthy control adults. All the study subjects were recruited from a valley (Val Vibrata valley) near Teramo, in the central part of Italy. The median Lp(a) oncentration of the whole group was 17 mg/dL (range 1–161 mg/dL), which is much higher than the values observed in Caucasian populations. No differences were detected between the octo- nonagenarian group (median 16 mg/dL, range 1–126 mg/dL) and the control group (median 19.5 mg/dL, range 1–161 mg/dL), nor between the free- living and the disabled groups. Apo(a) isoforms were similarly distributed among free- living, disabled and control subjects. While our findings suggest that Lp(a) plasma levels and apo(a) isoforms are not factors associated with longevity or disability, we cannot exclude that the low incidence of other major risk factors for atherosclerosis in our free- living octo- nonagenarians hampered the full expression of the lipoprotein(a) atherogenic potential, and thus allowed the achievement of a very old age in a good healthy status, even in carriers of high Lp(a) levels or small apo(a) isoforms.