APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality

Useless until you get your doctor to define what fatty acids are, what test will be needed to determine if you have the APOE gene, how to determine if you have enough circulating linoleic acid, and what is palmitic acid? In simple terms we need a protocol.

APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality

Claudia L. Satizabal

,

Cécilia Samieri

Kendra L. Davis-Plourde

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Barbara Voetsch

,

Hugo J. Aparicio

,

Matthew P. Pase

,

José Rafael Romero

,

Catherine Helmer

,

Ramachandran S. Vasan

, … Show all Authors

Originally published7 Nov 2018Stroke. 2018;0:STROKEAHA.118.022132

Abstract

Background and Purpose—

The role of dietary fat on cardiovascular health and mortality remains under debate. Because the APOE is central to the transport and metabolism of lipids, we examined associations between plasma fatty acids and the risk of stroke, coronary heart disease, and mortality by APOE-ε4 genotype.

Methods—

We included 943 FHS (Framingham Heart Study) and 1406 3C (Three-City) Bordeaux Study participants. Plasma docosahexaenoic, linoleic, arachidonic, and palmitic fatty acids were measured at baseline by gas chromatography. All-cause stroke, ischemic stroke, coronary heart disease, and all-cause mortality events were identified prospectively using standardized protocols. Each cohort used Cox models to separately relate fatty acid levels to the risk of developing each event during ≤10 years of follow-up adjusting for potential confounders and stratifying by APOE genotype (ε4 carriers versus noncarriers). We then meta-analyzed summary statistics using random-effects models.

Results—

On average, participants had a mean age of 74 years, 61% were women, and 21% (n=483) were APOE-ε4 carriers. Meta-analysis results showed that, only among APOE-ε4 carriers, every SD unit increase in linoleic acid was associated with a reduced risk of all-cause stroke (hazard ratio [HR], 0.54 [95% CI, 0.38–0.78]), ischemic stroke (HR, 0.48 [95% CI, 0.33–0.71]), and all-cause mortality (HR, 0.70 [95% CI, 0.57–0.85]). In contrast, every SD unit increase in palmitic acid was related to an increased risk of all-cause stroke (HR, 1.58 [95% CI, 1.16–2.17]), ischemic stroke (HR, 1.76 [95% CI, 1.26–2.45]), and coronary heart disease (HR, 1.48 [95% CI, 1.09–2.01]), also in APOE-ε4 carriers only. Results for docosahexaenoic acid and arachidonic acid were heterogeneous between cohorts.

Conclusions—

These exploratory results suggest that APOE-ε4 carriers may be more susceptible to the beneficial or adverse impact of fatty acids on cardiovascular disease and mortality. In this subgroup, higher linoleic acid was protective for stroke and mortality, whereas palmitic acid was a risk factor for stroke and coronary heart disease. The mechanisms underlying these novel findings warrant further investigation.

Footnotes

The online-only Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.118.022132.

Substitution of Linoleic Acid for Other Macronutrients and the Risk of Ischemic Stroke

You can't do anything with this until your doctor gets a diet stroke protocol written. You'd better hope she is the best in the world at this job.

But this statement from this in May 2016 suggests it is not useful, except it doesn't talk strokes. What to do?

Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)  May 2016

There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts.

And this from Oct. 2015 suggests it is helpful:

Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study  Oct. 2015 

High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.

 

 Substitution of Linoleic Acid for Other Macronutrients and the Risk of Ischemic Stroke

Stine K. Venø, Erik B. Schmidt, Marianne U. Jakobsen, Søren Lundbye-Christensen, Flemming W. Bach, Kim Overvad

https://doi.org/10.1161/STROKEAHA.117.017935

Stroke. 2017;48:3190-3195

Originally published October 25, 2017

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Abstract

Background and Purpose—Ischemic stroke is a major health problem worldwide, but the influence of dietary factors on stroke risk is not well known. This study aimed to investigate the risk of ischemic stroke and its subtypes with a higher intake from linoleic acid and a concomitant lower intake from saturated fatty acids, monounsaturated fatty acids, or glycemic carbohydrates.

Methods—In the Danish prospective Diet, Cancer, and Health Study of 57 053 participants aged 50 to 64 years at baseline, information on diet was collected using a validated semiquantitative food frequency questionnaire. Information on ischemic stroke was obtained from the Danish National Patient Register, and cases were all validated and subclassified according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Substitution of linoleic acid for saturated fatty acid, monounsaturated fatty acid, or glycemic carbohydrates was investigated in relation to the risk of ischemic stroke and subtypes. Cox proportional hazards regression was used to estimate the associations with ischemic stroke adjusting for appropriate confounders.

Results—During 13.5 years of follow-up 1879 participants developed ischemic stroke. A slightly lower risk of ischemic stroke was found with a 5% higher intake of linoleic acid and a concomitant lower intake of saturated fatty acid (hazard ratio, 0.98; 95% confidence interval, 0.83–1.16), monounsaturated fatty acid (hazard ratio, 0.80; 95% confidence interval, 0.63–1.02), and glycemic carbohydrates (hazard ratio, 0.92; 95% confidence interval, 0.78–1.09), although not statistically significant. Similar patterns of association were found for large-artery atherosclerosis and small-vessel occlusions.

Conclusions—This study suggests that replacing saturated fatty acid, glycemic carbohydrate, or monounsaturated fatty acid with linoleic acid may be associated with a lower risk of ischemic stroke.

Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)

It has only been out for three weeks, have your doctors instructed the hospital nutritionist to update the diet protocols? Or do they not even read research and you are fucking screwed forever?
Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)

BMJ 2016; 353 doi: http://dx.doi.org/10.1136/bmj.i1246 (Published 12 April 2016) Cite this as: BMJ 2016;353:i1246

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1. Christopher E Ramsden, medical investigator1 2,
2. Daisy Zamora, epidemiologist3,
3. Sharon Majchrzak-Hong, research chemist1,
4. Keturah R Faurot, epidemiologist2,
5. Steven K Broste, retired statistician4,
6. Robert P Frantz, professor of medicine5,
7. John M Davis, professor of psychiatry3 6,
8. Amit Ringel, guest researcher1,
9. Chirayath M Suchindran, senior biostatistician7,
10. Joseph R Hibbeln, senior clinical investigator1

Author affiliations

1. Correspondence to: C E Ramsden Chris.Ramsden@nih.gov

• Accepted 19 February 2016

Abstract

Objective To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis.

Design The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted.

Setting One nursing home and six state mental hospitals in Minnesota, United States.

Participants Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files.

Interventions Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings.

Main outcome measures Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy.

Results The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline −13.8% v −1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n=10 808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27).

Conclusions Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

Complete article at link if you want to try wading thru it.

Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study

Since this seems helpful the next obvious step is to create a stroke protocol for how to get Omega-6 PFAs to the helpful level in your bloodstream. Do not do this on your own. This is a job for that great stroke association in the sky, that doesn't exist yet. You're fucking screwed because we have no one putting all this research together into a coherent whole for stroke prevention and rehabilitation. The answers are out there, we just need a couple dozen geniuses to put this all together. This won't happen in our lifetimes because everyone in the stroke world is JUST WAITING FOR SOMEONE ELSE TO SOLVE THE PROBLEM!
I dare you to prove me wrong and that you have taken up this challenge.
Matt Lopez, president of the NSA?

Dr. Mariel Jessup, president of the ASA?
WSO President - Steve Davis (Australia)?   
Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study

Wu JH¹, Lemaitre RN², King IB², Song X², Psaty BM², Siscovick DS², Mozaffarian D².

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Abstract

BACKGROUND:

Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort.

METHODS AND RESULTS:

Among 2792 participants(aged ≥65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.

CONCLUSIONS:

High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.
Inversely meaning high levels of linoleic acid are associated with lower mortality.

Replacement of saturated fat with polyunsaturated fat may reduce CHD risk

Rather incomplete analysis, What about good saturated fat? For example, lauric acid found in coconut oil?
Replacement of saturated fat with polyunsaturated fat may reduce CHD risk

Higher intake of dietary linoleic acid is associated with lower risk for CHD in a dose-response manner, according to results of a systematic review and meta-analysis of prospective cohort studies.

“These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD,” Maryam S. Farvid, PhD, from the department of nutrition, Harvard School of Public Health, and colleagues wrote in Circulation.
The systematic review and meta-analysis focused on 13 prospective cohort studies that assessed the link between dietary intake of linoleic acid, the main polyunsaturated fat found in vegetable oil, nuts and seeds, and the incidence of CHD. Three trials did not report total CHD events, and four provided separate data for men and women, resulting in 14 estimates for total CHD. Two trials did not include data on CHD-related mortality and one reported separate data according to sex, resulting in 12 estimates for CHD mortality. Follow-up ranged from 5.3 years to 30 years across the studies.
Overall, the study population included 310,602 participants and 12,479 total CHD events (5,882 CHD deaths).
Dietary intake of linoleic acid ranged from 1.5% to 6.4% of energy.
Across 10 studies with evaluable data on total CHD events, participants with the highest intake of dietary linoleic acid had a reduced risk for CHD events (pooled RR=0.85; 95% CI, 0.78-0.92 vs. lowest reported intake) in a fixed-effects model. A random-effects model yielded similar results (RR=0.86; 95% CI, 0.76-0.97).
Across the 11 trials that provided evaluable data on CHD mortality, participants with the highest intake of linoleic acid were at reduced risk (pooled RR=0.79; 95% CI, 0.71-0.89 vs. lowest reported intake).
In a dose-response analysis, the researchers observed linear associations between dietary linoleic acid consumption and total CHD events (P=.91 for nonlinearity) and CHD-related mortality (P=.72). Each 5% increment of energy intake from linoleic acid was associated with reduced risk for CHD (RR=0.9; 95% CI, 0.85-0.94) and CHD mortality (RR=0.87; 95% CI, 0.81-0.93).
Analysis of data from eight trials that assessed the substitution of 5% of caloric intake from saturated fats with linoleic acid indicated a 9% reduction in risk in a fixed-effects model (RR=0.91; 95% CI, 0.87-0.96) and a 10% reduction in a random-effects model (OR=0.9; 95% CI; 0.8-1.01). Substitution of 5% of caloric intake from carbohydrates for linoleic acid yielded similar results for total CHD (RR=0.9; 95% CI, 0.85-0.94) and CHD-related mortality (RR=0.87; 95% CI, 0.81-0.94).
According to the researchers, these results provide “robust evidence” of a dose-response relationship between increased linoleic acid intake and reduced CHD risk.
“Randomized clinical trials have shown that replacing saturated fat with polyunsaturated fat reduces total and HDL cholesterol,” Frank B. Hu, MD, PhD, professor of nutrition and epidemiology at Harvard School of Public Health, said in a press release. “Our comprehensive meta-analysis provides clear evidence to support the benefits of consuming polyunsaturated fat as a replacement for saturated fat.”