RESUMO
Inflammation in elderly is associated with physical and cognitive morbidity and mortality. We aimed to explore the association of modifiable lifestyle parameters with inflammation among non-demented, community-dwelling elderly. A sub-sample of 117 patients with mild cognitive impairment (MCI, n = 63) and cognitively non-impaired controls (CNI, n = 54) were recruited from a large, population-based cohort in Crete, Greece, of 3140 elders (>60 years old). All participants underwent assessment of medical history/physical examination, extensive neuropsychiatric/neuropsychological evaluation, diet, three-day 24-h actigraphy, subjective sleep, physical activity, and measurement of IL-6 and TNFα plasma levels. Associations between inflammatory markers and diet, objective sleep duration, subjective sleep quality, and lack of physical activity were assessed using multivariate models. Regression analyses in the total group revealed significant associations between TNF-α and low vegetable consumption (p = 0.003), and marginally with objective long nighttime sleep duration (p = 0.04). In addition, IL-6 was associated with low vegetable consumption (p = 0.001) and lack of physical activity (p = 0.001). Poor diet and lack of physical activity appear to be modifiable risk factors of inflammation, whereas long sleep appears to be a marker of increased inflammatory response in elderly. Our findings may have clinical implications given the association of inflammatory response with morbidity, including cognitive decline, and mortality in elderly.
RESUMO
RATIONALE & OBJECTIVE: Lecithin-cholesterol acyltransferase (LCAT) catalyzes the maturation of high-density lipoprotein. Homozygosity for loss-of-function mutations causes familial LCAT deficiency (FLD), characterized by corneal opacities, anemia, and renal involvement. This study sought to characterize kidney biopsy findings and clinical outcomes in a family with FLD. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 2 (related) index patients with clinically apparent FLD were initially identified. 110 of 122 family members who consented to genetic analysis were also studied. PREDICTORS: Demographic and laboratory parameters (including lipid profiles and LCAT activity) and full sequence analysis of the LCAT gene. Kidney histologic examination was performed with samples from 6 participants. OUTCOMES: Cardiovascular and renal events during a median follow-up of 12 years. Estimation of annual rate of decline in glomerular filtration rate. ANALYTICAL APPROACH: Analysis of variance, linear regression analysis, and Fine-Gray competing-risk survival analysis. RESULTS: 9 homozygous, 57 heterozygous, and 44 unaffected family members were identified. In all affected individuals, full sequence analysis of the LCAT gene revealed a mutation (c.820C>T) predicted to cause a proline to serine substitution at amino acid 274 (P274S). Homozygosity caused a complete loss of LCAT activity. Kidney biopsy findings demonstrated lipid deposition causing glomerular basement membrane thickening, mesangial expansion, and "foam-cell" infiltration of kidney tissue. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with worse kidney outcomes. Estimated glomerular filtration rate deteriorated among homozygous family members at an average annual rate of 3.56 mL/min/1.73 m2. The incidence of cardiovascular and renal complications was higher among homozygous family members compared with heterozygous and unaffected members. Mild thrombocytopenia was a common finding among homozygous participants. LIMITATIONS: The presence of cardiovascular disease was mainly based on medical history. CONCLUSIONS: The P274S LCAT mutation was found to cause FLD with renal involvement. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with a worse renal prognosis.
