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In this study we assessed whether widely accepted risk factors for atherosclerotic vascular diseases such as lipoprotein(a) [Lp(a)], a cholesterol-rich lipoprotein under strict genetical control, and other lipid parameters change with age. The variations of blood levels and the pathophysiological role of Lp(a) in old people, and particularly in the oldest old, are unknown. Accordingly, we measured Lp(a) levels as well as total, LDL, and HDL cholesterol (CT), and triglycerides (TG) in sera from 75 healthy centenarians, 114 randomly selected subjects under 65 years, 73 randomly selected elderly people, and 30 healthy selected elderly people. The results showed that Lp(a) serum levels did not vary by age group, including centenarians. Remarkably, one-quarter of the centenarians had high Lp(a) serum levels even though they never suffered from atherosclerosis-related diseases. At variance with young and aged people, centenarians with high Lp(a) serum levels also had high plasma concentrations of the proinflammatory cytokine IL-6, suggesting that genetic control of the Lp(a) serum level may attenuate with age and that environmental factors such as chronic subclinical inflammatory processes may play a role. We also showed that most centenarians are paradoxically characterized by low HDL-CT and relatively high TG levels, which together are considered to be strong risk factors for coronary heart disease. On the whole, these data support the hypothesis that a continuous and complex reshaping of lipid metabolism occurs in physiological aging, likely contributing to successful aging.

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BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disease characterised by the growth of uncapsulated masses of adipose tissue. MSL is associated with high ethanol intake and complicated by somatic and autonomic neuropathy and the infiltration of adipose tissue at the mediastinal level. To date, the disease is considered as largely more prevalent in men. OBJECTIVE: To provide a detailed description of the clinical aspects of MSL in women. PATIENTS: A total of 11 women and 58 men with MSL. MEASUREMENTS: Morphological aspect of patient, location of the lipomatous masses, alcohol intake, extension of lipomatous tissue to the mediastinum, association with somatic and autonomic neuropathy, and metabolic profile. RESULTS: All female patients had the obesity-like appearance of type II MSL and the most frequent locations of lipomatous masses in women were at the proximal arms (90.9%) and legs (54.5%). Very few female patients (27.3%) presented with the submental deposition of lipomatous tissue typical of both type I (97.3%; Po0.001) and type II (66.7%; Po0.05) male subjects. An extension of the lipomatus tissue around the upper airways, associated with compression or dislocation of deeply located mediastinal structures, was observed less frequently in women than in men. The presence of a high ethanol intake, the association with somatic and autonomic neuropathy and the occurrence of a characteristic metabolic pattern (high HDLcholesterol, low LDL-cholesterol, high uric acid) were similar in men and in women. CONCLUSIONS: Female patients with MSL had a sex-specific morphological aspect, characterised by a low occurrence of the typical 'Madelung collar' and a usual obesity-like appearance.

Background: Since emerging evidence suggests a protective role of proprotein convertase subtilisin/kexin type 9 (PCSK9) on hepatitis C virus (HCV) infection, the aim of the present study was to evaluate the correlation between PCSK9 and HCV infection in hepatocellular carcinoma (HCC) patients. Methods: In this retrospective study, PCSK9 levels were evaluated by ELISA, in plasma samples from control (n = 24) and 178 patients diagnosed for HCC, cirrhosis, or chronic hepatitis, either positive or negative for HCV. Results: HCV positive patients (HCV+) presented with higher PCSK9 levels compared to HCV negative individuals (HCV-), 325.2 ± 117.7 ng/mL and 256.7 ± 139.5 ng/mL, respectively. This difference was maintained in the presence of HCC, although this disease significantly reduced PCSK9 levels. By univariate analysis, a positive correlation between PCSK9 and HCV viral titer was found, being G2 genotype the most-potent inducer of PCSK9 among other genotypes. This induction was not associated with changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). A negative correlation was also found between PCSK9 levels and liver impairment, assessed by Model for End-Stage Liver Disease (MELD). Finally, a multivariate correlation analysis corrected for age, TC, LDL-C, and sex, demonstrated, in the whole cohort, a positive association between PCSK9 and HCV and a negative with HCC. Conclusions: taken together, our study reveals that HCV raised PCSK9 in both the presence and absence of HCC.