scholarly journals Plasma phospholipid and dietary α-linolenic acid, mortality, CHD and stroke: the Cardiovascular Health Study

2014 ◽  
Vol 112 (7) ◽  
pp. 1206-1213 ◽  
Author(s):  
Amanda M. Fretts ◽  
Dariush Mozaffarian ◽  
David S. Siscovick ◽  
Colleen Sitlani ◽  
Bruce M. Psaty ◽  
...  

Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Amanda M Fretts ◽  
Dariush Mozaffarian ◽  
David Siscovick ◽  
Colleen Sitlani ◽  
Bruce M Psaty ◽  
...  

Objective: To examine the association of α-linolenic acid (ALA 18:3n-3), an essential n-3 fatty acid derived from plants and vegetable oils, with mortality, coronary heart disease, and stroke among older adults. Due to the low correlation between dietary and circulating ALA that may reflect differences in diet and metabolism, we evaluated plasma phospholipid ALA and dietary ALA separately. Methods: The study population included participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and stroke. A total of 2,709 participants comprised the plasma phospholipid analysis group and 4,214 participants comprised the dietary analysis group. Plasma phospholipid ALA, an objective measure of circulating levels of ALA over the past 4-8 weeks, was measured using stored samples from 1992-1993. Dietary fatty acid intake was ascertained using food frequency questionnaires administered in 1989 and 1996. ALA was expressed as percent of total fatty acids and percent of total dietary fat for the plasma phospholipid and dietary analyses, respectively. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with mortality, and incident coronary heart disease or stroke. Results: Dietary ALA and plasma phospholipid ALA were modestly correlated (r=0.18). We found no statistically significant associations of plasma phospholipid ALA with mortality, incident CHD or stroke (table). After adjustment for potential confounders, dietary intake of ALA was associated with a lower risk of total and non-CVD mortality. We found no statistically significant associations of dietary ALA with CVD mortality, incident CHD or stroke (table). Conclusions: Results from this prospective cohort study of older adults suggest that dietary, but not plasma phospholipid ALA, is associated with a lower risk of total and non-CVD mortality in older adults.


2021 ◽  
Author(s):  
Amanda M Fretts ◽  
Paul N Jensen ◽  
Andrew N Hoofnagle ◽  
Barbara McKnight ◽  
Colleen M Sitlani ◽  
...  

Abstract Background Recent studies suggest that associations of ceramides (Cer) and sphingomyelins (SM) with health outcomes differ according to the fatty acid acylated to the sphingoid backbone. The purpose of this study was to assess associations of Cer and SM species with mortality. Methods The study population included participants from the Cardiovascular Health Study (CHS), a community-based cohort of adults aged ≥65 years who were followed from 1992–2015 (n = 4612). Associations of plasma Cer and SM species carrying long-chain (i.e., 16:0) and very-long-chain (i.e., 20:0, 22:0, 24:0) saturated fatty acids with mortality were assessed using Cox proportional hazards models. Results During a median follow-up of 10.2 years, 4099 deaths occurred. High concentrations of Cer and SM carrying fatty acid 16:0 were each associated with an increased risk of mortality. Conversely, high concentrations of several ceramide and sphingomyelin species carrying longer fatty acids were each associated with a decreased risk of mortality. The hazard ratios for total mortality per 2-fold difference in each Cer and SM species were: 1.89 (95% CI), 1.65–2.17 for Cer-16, 0.79 (95% CI, 0.70–0.88) for Cer-22, 0.74 (95% CI, 0.65–0.84) for Cer-24, 2.51 (95% CI, 2.01–3.14) for SM-16, 0.68 (95% CI, 0.58–0.79) for SM-20, 0.57 (95% CI, 0.49–0.67) for SM-22, and 0.66 (0.57–0.75) for SM-24. We found no association of Cer-20 with risk of death. Conclusions Associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid. Future studies are needed to explore mechanisms underlying these relationships.


Heart ◽  
2011 ◽  
Vol 97 (6) ◽  
pp. 500-505 ◽  
Author(s):  
S. Win ◽  
K. Parakh ◽  
C. M. Eze-Nliam ◽  
J. S. Gottdiener ◽  
W. J. Kop ◽  
...  

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Qianyi Wang ◽  
Fumiaki Imamura ◽  
Wenjie Ma ◽  
Rozenn N Lemaitre ◽  
Irena B King ◽  
...  

Background: While trans-fatty acids (TFA) influence CHD, their effects on type 2 diabetes mellitus (DM) are not established, with mixed findings of experimental, short-term intervention, and observational studies. Effects may vary depending on specific TFA subtype or method of assessment (circulating biomarkers vs. diet). Objectives: To examine prospective associations of circulating and estimated dietary TFA with risk of incident DM in older adults. Methods: Plasma phospholipid trans-(t-)16:1n9, total t-18:1, and cis/trans-(c/t-), t/c- and t/t-18:2(n6,9) were measured in blood stored among 3,076 adults in the Cardiovascular Health Study (CHS), aged 74±5y and free of prevalent DM in 1992. Dietary TFA was estimated among 4,246 adults free of prevalent DM when dietary questionnaires were initially administered in 1989 (n=3,917) or in 1996 (n=329). Incident DM up to 2009 was defined as new use of insulin or hypoglycemic drugs, fasting glucose≥126 mg/dL, nonfasting glucose≥200 mg/dL, or 2-hour post-challenge glucose≥200 mg/dL. The relative risk of incident DM associated with each TFA subtype was assessed using multivariate Cox proportional hazards regression. Results: Levels of each circulating TFA subtype varied from 2.00±0.73 (% of fatty acids) for t-18:1 to 0.05±0.02 for t/t-18:2. TFA subtypes were moderately to highly intercorrelated (r=0.4 to 0.8), except for t/t-18:2 which weakly correlated with all other TFAs (r<0.1). During 30,927 person-years, 364 DM cases occurred among participants with plasma phospholipid TFA measures. Adjusting for demographics, lifestyle factors, and medical history, lower DM risk was associated with higher levels of t-16:1n9 (Quartile 4 vs. Quartile 1 HR=0.76, p trend=0.03), total t-18:1 (HR=0.71, p trend=0.02) and t/t-18:2 (HR=0.73, p trend=0.04). However, further mutual adjustment for the different TFA subtypes attenuated these inverse associations, and none of the 5 circulating TFA biomarkers were independently related to incident DM (p trend≥0.14 for all). During 50,508 person-years in the dietary analyses, 453 DM cases occurred. Adjusting for demographics, lifestyle, medical history, and other dietary habits, increased DM risk was observed among participants with higher consumption of total TFA (Quartile 4 vs. Quartile 1 HR=1.40, p trend=0.04) and t-18:2 (HR=1.49, p trend=0.006), and t-18:1 consumption (HR=1.32, p trend=0.08), although the latter was not statistically significant. Conclusions: Plasma phospholipid TFA subtypes were not associated, whereas dietary total TFA and t-18:2 were positively associated, with incident DM among older adults. These findings highlight the need to understand how dietary TFA may influence DM and why associations may differ for circulating versus dietary TFAs.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Amanda M Fretts ◽  
Paul Jensen ◽  
Andrew Hoofnagle ◽  
Barbara McKnight ◽  
Colleen Sitlani ◽  
...  

Introduction: Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences sphingolipid activity, and that associations of ceramides (Cer) and sphingomyelins (SM) with cardiovascular outcomes may differ by lipid species. The purpose of this study was to assess associations of Cer and SM species with mortality among 4,612 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992-2015. Hypothesis: Higher levels of circulating Cer and SM with palmitic acid (Cer-16) are associated with a higher risk of mortality (i.e., deaths from cardiovascular disease (CVD) and non-cardiovascular causes) while higher levels of Cer and SM with very-long chain saturated fatty acids arachidic acid (Cer-20 and SM-20), behenic acid (Cer-22 and SM-22), and lignoceric acid (Cer-24 and SM-24) are associated with a lower risk. Methods: The associations of each sphingolipid with mortality were assessed using Cox proportional hazards models. Models adjusted for age, sex, self-reported race, geographic area, education, smoking, alcohol use, BMI, activities of daily living, HDL and LDL cholesterol, triglycerides, systolic blood pressure, physical activity, use of hypertension or lipid-lowering drugs, self-reported health status, prevalent diabetes, CVD, heart failure (HF), and other sphingolipids species. Results: During a median follow-up of 10.2 years (range 0-23 years), 4,099 deaths occurred. At each time, higher levels of Cer-16 and SM-16 were associated with a higher risk of mortality, while higher levels of Cer-22, Cer-24, SM-20, SM-22, and SM-24 were associated with a lower risk of mortality (Figure). Models that did not adjust for diabetes, CVD, and HF produced similar results. Conclusions: These findings suggest that the associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid, and support the need for future studies to explore mechanisms underlying these relations.


BMJ ◽  
2018 ◽  
pp. k4067 ◽  
Author(s):  
Heidi TM Lai ◽  
Marcia C de Oliveira Otto ◽  
Rozenn N Lemaitre ◽  
Barbara McKnight ◽  
Xiaoling Song ◽  
...  

AbstractObjectiveTo determine the longitudinal association between serial biomarker measures of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) levels and healthy ageing.DesignProspective cohort study.SettingFour communities in the United States (Cardiovascular Health Study) from 1992 to 2015.Participants2622 adults with a mean (SD) age of 74.4 (4.8) and with successful healthy ageing at baseline in 1992-93.ExposureCumulative levels of plasma phospholipid n3-PUFAs were measured using gas chromatography in 1992-93, 1998-99, and 2005-06, expressed as percentage of total fatty acids, including α-linolenic acid from plants and eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid from seafoood.Main outcome measureHealthy ageing defined as survival without chronic diseases (ie, cardiovascular disease, cancer, lung disease, and severe chronic kidney disease), the absence of cognitive and physical dysfunction, or death from other causes not part of the healthy ageing outcome after age 65. Events were centrally adjudicated or determined from medical records and diagnostic tests.ResultsHigher levels of long chain n3-PUFAs were associated with an 18% lower risk (95% confidence interval 7% to 28%) of unhealthy ageing per interquintile range after multivariable adjustments with time-varying exposure and covariates. Individually, higher eicosapentaenoic acid and docosapentaenoic acid (but not docosahexaenoic acid) levels were associated with a lower risk: 15% (6% to 23%) and 16% (6% to 25%), respectively. α-linolenic acid from plants was not noticeably associated with unhealthy ageing (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02).ConclusionsIn older adults, a higher cumulative level of serially measured circulating n3-PUFAs from seafood (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid), eicosapentaenoic acid, and docosapentaenoic acid (but not docosahexaenoic acid from seafood or α-linolenic acid from plants) was associated with a higher likelihood of healthy ageing. These findings support guidelines for increased dietary consumption of n3-PUFAs in older adults.


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