scholarly journals Serum Nonesterified Fatty Acids and Incident Stroke: The CHS

Author(s):  
Neil K. Huang ◽  
Mary L. Biggs ◽  
Nirupa R. Matthan ◽  
Luc Djoussé ◽  
W. T. Longstreth ◽  
...  

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and trans fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996–1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)‐6 polyunsaturated, n‐3 polyunsaturated, and trans fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5‐year follow‐up period. Total n‐3 (hazard ratio [HR], 0.77 [95% CI, 0.61–0.97]) and n‐6 (HR, 1.32 [95% CI, 1.01–1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo‐γ‐linolenic acid (20:3n‐6) was associated with higher risk (HR, 1.29 [95% CI, 1.02–1.63]), whereas cis ‐7‐hexadecenoic acid (16:1n‐9 c ) and arachidonic acid (20:4n‐6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47–0.97]; HR, 0.81 [95% CI. 0.65–1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n‐3 subclass and dihomo‐γ‐linolenic acid are diet derived and may be potential biomarkers for total stroke risk.

Author(s):  
Peter D Ahiawodzi ◽  
Petra Buzkova ◽  
Luc Djousse ◽  
Joachim H Ix ◽  
Jorge R Kizer ◽  
...  

Abstract Background We sought to determine associations between total serum concentrations of nonesterified fatty acids (NEFAs) and incident total and cause-specific hospitalizations in a community-living cohort of older adults. Methods We included 4715 participants in the Cardiovascular Health Study who had fasting total serum NEFA measured at the 1992/1993 clinic visit and were followed for a median of 12 years. We identified all inpatient admissions requiring at least an overnight hospitalization and used primary diagnostic codes to categorize cause-specific hospitalizations. We used Cox proportional hazards regression models to determine associations with time-to-first hospitalization and Poisson regression for the rate ratios (RRs) of hospitalizations and days hospitalized. Results We identified 21 339 hospitalizations during follow-up. In fully adjusted models, higher total NEFAs were significantly associated with higher risk of incident hospitalization (hazard ratio [HR] per SD [0.2 mEq/L] = 1.07, 95% confidence interval [CI] = 1.03–1.10, p < .001), number of hospitalizations (RR per SD = 1.04, 95% CI = 1.01–1.07, p = .01), and total number of days hospitalized (RR per SD = 1.06, 95% CI = 1.01–1.10, p = .01). Among hospitalization subtypes, higher NEFA was associated with higher likelihood of mental, neurologic, respiratory, and musculoskeletal causes of hospitalization. Among specific causes of hospitalization, higher NEFA was associated with diabetes, pneumonia, and gastrointestinal hemorrhage. Conclusions Higher fasting total serum NEFAs are associated with a broad array of causes of hospitalization among older adults. While some of these were expected, our results illustrate a possible utility of NEFAs as biomarkers for risk of hospitalization, and total days hospitalized, in older adults. Further research is needed to determine whether interventions based on NEFAs might be feasible.


Cardiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Luc Djousse ◽  
Mary L. Biggs ◽  
Nirupa R. Matthan ◽  
Joachim H. Ix ◽  
Annette L. Fitzpatrick ◽  
...  

Background: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined. Objective: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults. Methods: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee. Results: The mean age was 77.7 ± 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57–0.94]), γ-linolenic acid (GLA) (0.87 [0.75–1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61–0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04–1.63]) and nervonic (24:1n-9) (1.17 [1.06–1.29]) acids with HF. Conclusion: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Fumiaki Imamura ◽  
Rozenn N Lemaitre ◽  
Irena King ◽  
Xiaoling Song ◽  
David S Siscovick ◽  
...  

Background: Decades-old animal experiments demonstrated that consumption of large amounts of long-chain monounsaturated fatty acids (LCMUFA, 22:1 and 24:1 fatty acids) caused cardiotoxicity. We recently found that plasma phospholipid 22:1 and 24:1 were associated with higher incidence of congestive heart failure (CHF) in two independent cohorts: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities Study. However, their association with incident CHD is unknown. Aim: to investigate association of plasma phospholipid 22:1 and 24:1 levels with incident CHD. Methods: The study included 3,221 adults free of CHD (age=74.9±5.2) in CHS in whom plasma phospholipid LCMUFA were measured in 1992. Incident CHD events from 1992 to 2006 were centrally adjudicated, and we assessed total CHD, including fatal CHD (fatal MI and other CHD deaths) and non-fatal MI. We examined prospective associations of LCMUFA with incident CHD using Cox proportional hazards. We further evaluated potential confounding or mediation by baseline risk factors and incident CHF. Results: Mean±SD phospholipid levels of 22:1 and 24:1 were 0.03±0.01 and 1.96±0.44 percent of total fatty acids. During 34,776 person-years, 628 incident CHD events occurred, including 309 fatal CHD and 401 non-fatal MIs. After multivariable adjustment, higher levels of both 22:1 and 24:1 were associated with higher risk of total incident CHD. Hazard ratios (95% CI) for quintiles 5 vs. 1 of 22:1 and 24:1 levels were 1.48 (1.07-2.06, p trend=0.005) and 1.65 (1.16-2.34, p trend=0.001). The associations with CHD were largely specific to fatal CHD rather than non-fatal MI (Figure). These associations did not change after adjustment for incident CHF and baseline risk factors including circulating lipids, blood pressure, and inflammatory markers. Conclusions: Higher levels of circulating 22:1 and 24:1 LCMUFA were associated with higher incidence of CHD, in particular fatal CHD, supporting the possibility of cardiotoxicity by current levels of LCMUFA exposure.


2021 ◽  
Vol 10 (6) ◽  
Author(s):  
Neil K. Huang ◽  
Petra Bůžková ◽  
Nirupa R. Matthan ◽  
Luc Djoussé ◽  
Calvin H. Hirsch ◽  
...  

Background Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n‐6 and n‐3], and trans fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. Methods and Results CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996–1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow‐up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P =0.0328) and dihomo‐γ‐linolenic acid (20:3n‐6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02–1.76; P =0.0351). Elaidic acid (18:1n‐7 t ) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01–2.12; P =0.0445). No significant associations were observed for NEFA subclass and any outcomes. Conclusions In CHS participants, 2 NEFAs, dihomo‐γ‐linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Stephanie Lyden ◽  
Adam DeHavenon ◽  
Vivek Reddy ◽  
Jennifer Majersik

Background: Studies have found an association between elevated serum C reactive protein (CRP) levels and increased ischemic stroke risk 2,4-5 . Other studies have looked at whether CRP levels correlate with outcome and severity after ICH 1,3 . Less research has been done looking at CRP levels and the risk for hemorrhagic stroke. This study aims to confirm the association of baseline elevated serum CRP levels and increased risk for ischemic stroke, thus validating this dataset, and to evaluate whether these levels correlate with an increased risk for hemorrhagic stroke. Methods: This is a secondary analysis of the data from the Cardiovascular Health Study (CHS). The primary outcome is ischemic stroke and the secondary outcome is hemorrhagic stroke. The primary predictor is CRP level at baseline, as a continuous value and, after dividing into quintiles, a comparison between the lowest and highest quintiles. We fit Cox proportional hazards models and adjusted for baseline covariates that were associated with the outcomes, which for ischemic stroke included age, race, cholesterol, diabetes, hypertension, atrial fibrillation, and history of TIA or myocardial infarction; and for hemorrhagic stroke included age, cholesterol, diabetes, and hypertension. Results: We included 5,681 patients, of whom 918 (16.2%) had ischemic stroke and 150 (2.6%) had hemorrhagic stroke. Mean (SD) days of follow-up was 4,403 (2,504) and mean (SD) CRP was 4.8 (8.3). We found that baseline CRP was associated with ischemic stroke (HR 1.01, 95% CI 1.00-1.02, p=0.005), but not hemorrhagic stroke (HR 1.00, 95% CI 0.97-1.02, p=0.781). When comparing the highest to lowest quintile of CRP, we found a clinically significant increased risk of ischemic stroke (HR 1.37, 95% CI 1.11-1.70, p=0.004) (Figure 1), but again not for hemorrhagic stroke (p=0.852). Conclusion: Our analysis found that elevated baseline CRP levels are associated with an increased risk for ischemic stroke, but not hemorrhagic stroke.


1970 ◽  
Vol 46 (2) ◽  
pp. 342-353 ◽  
Author(s):  
Samuel W. Cushman

Pinocytic activity in the adipose cell has been examined by measuring the uptake of colloidal gold. Pinocytic activity occurs in the isolated adipose cell under all experimental conditions; a portion of the vesicular elements of the cell can be identified by electron microscopy as pinocytic in origin. The isolated adipose cell appears to take up serum albumin by pinocytosis. Pinocytic activity in the isolated adipose cell is enhanced by epinephrine, but not by insulin. The relationship between pinocytosis and the metabolic activity of the adipose cell has been studied by measuring simultaneously the uptake of radioactive colloidal gold, the incorporation of 14C-counts from U-glucose-14C into CO2, total lipid, triglyceride glycerol and triglyceride fatty acids, and the release of nonesterified fatty acids in the absence of hormones and in the presence of insulin or epinephrine. Correlations between hormone-produced alterations in lipid metabolism and in pinocytic activity suggest that intracellular nonesterified fatty acid levels are a factor in the regulation of both the cell's pinocytic activity and its metabolism and that pinocytosis in the adipose cell functions in the extracellular-intracellular transport of nonesterified fatty acids.


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