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Association between Cholesterol Exposure and Neuropathological Findings: The ACT Study.

ABSTRACT: We characterized the relationship between late life cholesterol exposure and neuropathological outcomes in a community-based, older adult cohort. Adult Changes in Thought (ACT) is a cohort study that enrolls consenting, randomly selected, non-demented people aged ?65 from a healthcare delivery system. We used late life HDL and total cholesterol lab values from Group Health computerized records, and calculated HDL and non-HDL levels. We evaluated neuropathological outcomes of Alzheimer's disease, cerebral amyloid angiopathy, vascular brain injury, and Lewy body disease. Using linear mixed models with age and antilipemic medication as predictors, we obtained predicted cholesterol values at age 70 and 10 years prior to death for individuals with available cholesterol data in 10-year exposure windows. We used logistic regression to determine whether predicted late life cholesterol levels were associated with neuropathological outcomes controlling for age at death, APOE genotype, sex, and their interactions with cholesterol levels. 525 decedents came to autopsy by 08/2014. Of these, plasma cholesterol concentration was available for 318 (age 70, model 1) and 396 (10 years prior to death, model 2) participants. We did not find associations between late life cholesterol and Alzheimer's disease neuropathological changes, and there were no associations between cholesterol levels and amyloid angiopathy or vascular brain injury. We observed an association between predicted non-HDL cholesterol at age 70 and Lewy body disease. Our study suggests an association between late life non-HDL cholesterol exposure and Lewy body disease. We did not observe associations between late life cholesterol levels and Braak stage or CERAD score.

SUBMITTER: Bettcher BM

PROVIDER: S-EPMC5604311 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association between Cholesterol Exposure and Neuropathological Findings: The ACT Study.

Bettcher Brianne M BM Ard M Colin MC Reed Bruce R BR Benitez Andreana A Simmons Amanda A Larson Eric B EB Sonnen Josh A JA Montine Thomas J TJ Li Ge G Keene C Dirk CD Crane Paul K PK Mungas Dan D

Journal of Alzheimer's disease : JAD 20170101 4

We characterized the relationship between late life cholesterol exposure and neuropathological outcomes in a community-based, older adult cohort. Adult Changes in Thought (ACT) is a cohort study that enrolls consenting, randomly selected, non-demented people aged ≥65 from a healthcare delivery system. We used late life HDL and total cholesterol lab values from Group Health computerized records, and calculated HDL and non-HDL levels. We evaluated neuropathological outcomes of Alzheimer's disease, ...[more]

PMID: 28731431

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Project description:Previous experimental studies showed that increasing high-density lipoprotein cholesterol (HDL) cholesterol shortens cardiac ventricular repolarization and the QT interval corrected for heart rate (QTc). However, little is known about the epidemiological relationship between HDL and QTc. The potential antiarrhythmic effect of HDL cholesterol remains a speculative hypothesis. In this cross-sectional population based study in adults living in the Italian-speaking part of Switzerland, we aimed to explore the association between HDL cholesterol and the QTc interval in the general population. A total of 1202 subjects were screened. electrocardiogram (ECG) recordings, measurements of lipid parameters and other laboratory tests were performed. QTc was corrected using Bazett's (QTcBaz) and Framingham (QTcFram) formulas. HDL was categorized according to percentile distributions: <25th (HDL-1; ?1.39 mmol/L); 25th-<50th (HDL-2; 1.40-1.69 mmol/L); 50th-<75th (HDL-3; 1.69-1.99 mmol/L); and ?75th (HDL-4; ?2.0 mmol/L). After exclusion procedures, data of 1085 subjects were analyzed. Compared with the HDL reference group (HDL-1), HDL-2 and HDL-3 were associated with a reduction of QTcBaz and QTcFram duration in crude (HDL-2, QTcBaz/QTcFram: ?-11.306/-10.186, SE 4.625/4.016; p = 0.016/0.012; HDL-3, ?-12.347/-12.048, SE 4.875/4.233, p = 0.012/<0.001) and adjusted (HDL-2: ?-11.697/-10.908, SE 4.333/4.151, p < 0.001/0.010; HDL-3 ?-11.786/-11.002, SE 4.719/4.521, p = 0.014/0.016) linear regression models in women. In adjusted logistic regression models higher HDL, were also associated with lower risk of prolonged QTcBaz/QTcFram (HDL-2: OR 0.16/0.17, CI 0.03-0.83/0.47-0.65; HDL-3: OR 0.10/0.14, CI 0.10-0.64/0.03-0.63) in women. Restricted cubic spline analysis confirmed a non linear association (p < 0.001). The present findings indicate an epidemiological association between HDL cholesterol and QTc duration. To draw firm conclusions, further investigations in other populations and with a prospective cohort design are needed.

Project description:ObjectivePrevious epidemiological studies have found an association between serum cholesterol level and bone mineral density. However, epidemiological studies evaluating the association between serum cholesterol level and the incidence of osteoporotic fracture are scant. Therefore, the objective of this study was to investigate whether serum cholesterol levels in Chinese participants aged 55?years or older was associated with an increased risk of osteoporotic fracture.Materials and methodsWe performed a cross-sectional study, including 1,791 participants (62.1% postmenopausal women and 213 fractures). Standardized self-administered questionnaires, physical examination, laboratory tests, and dual-energy X-ray absorptiometry examination were performed. Multivariate-adjusted logistic regression models were used to evaluate associations between serum cholesterol [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C)] levels and the osteoporotic fracture risk.ResultsAfter adjusting for potential confounding factors, there were no associations between per SD increase in TC and LDL level and an increased risk of osteoporotic fracture in total participants, and in men and women as individual groups. There was a significant association between per SD increase in HDL-C level and an increased risk of osteoporotic fracture in total participants [odds ratios (OR) 1.20, 95% confidence interval (CI) 1.03, 1.40, P?=?0.023] and in women (OR 1.37, 95% CI 1.12, 1.68, P?=?0.003), whereas no association was observed in men (OR 1.01, 95% CI 0.73, 1.40, P?=?0.951). Additionally, we found a significant association between per SD increase in TG level and an increased risk of osteoporotic fracture in total participants (OR 1.20, 95% CI 1.04, 1.38, P?=?0.015). In women, a nonlinear relationship was observed between per SD increase in TG level and an increased risk of osteoporotic fracture. The risk of osteoporotic fracture in women increased with TG level >1.64?mmol/L (OR 1.93, 95% CI 1.24, 3.00, P?=?0.004).ConclusionAmong Chinese older adults, serum HDL-C level is significantly associated with a risk of osteoporotic fractures in women, and serum TG level is significantly associated with a risk of osteoporotic fractures in total participants and in women with TG >1.64?mmol/L.

Project description:ImportanceLow-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease (CVD). Most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk.ObjectiveTo evaluate the associations of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age with incident CVD later in life.Design, setting, and participantsThis cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021.ExposuresCumulative exposure to LDL-C, TWA LDL-C, and LDL-C slope from age 18 to 60 years.Main outcomes and measuresIncident coronary heart disease (CHD), ischemic stroke, and heart failure (HF).ResultsA total of 18 288 participants were included in this study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 HF events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level, 1.69 (95% CI, 1.23-2.31; P for trend <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69-1.12; P for trend = .28) for LDL-C slope. No association was found between any of the LDL-C variables and ischemic stroke or HF.Conclusions and relevanceThis cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.

Dataset Information

Association between Cholesterol Exposure and Neuropathological Findings: The ACT Study.

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Association between Cholesterol Exposure and Neuropathological Findings: The ACT Study.

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