Dataset Information

Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis.

ABSTRACT:

Objective

To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death.

Design

Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data.

Setting

Ambulatory, coronary care clinic in Sydney, Australia.

Participants

458 men aged 30-59 years with a recent coronary event.

Interventions

Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups.

Outcome measures

All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group.

Results

The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07).

Conclusions

Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats.

Trial registration

Clinical trials NCT01621087.

SUBMITTER: Ramsden CE

PROVIDER: S-EPMC4688426 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Previous systematic reviews were not restricted to either primary or secondary prevention trials, this study aimed to investigate the effects of reduced and/or modified fat diets and dietary fatty acids on all-cause mortality, cardiovascular mortality and cardiovascular events in participants with established coronary heart disease.Systematic review, meta-analysis and univariate/multivariate meta-regression.Electronic searches for randomised controlled trials comparing reduced/modified fat diets versus control diets were performed in MEDLINE, EMBASE and the Cochrane Library.Pooled effects were calculated using an inverse-variance random effect meta-analysis. Random effects univariate and multivariate meta-regressions were performed including changes in all types of dietary fatty acids.Overall, 12 studies enrolling 7150 participants were included in the present systematic review. No significant risk reduction could be observed considering all-cause mortality (relative risk (RR) 0.92, p=0.60; I(2)=59%) and cardiovascular mortality (RR 0.96, p=0.84; I(2)=69%), combined cardiovascular events (RR 0.85, p=0.30; I(2)=75%) and myocardial infarction (RR 0.76, p=0.13; I(2)=55%) comparing modified fat diets versus control diets. This results could be confirmed for the reduced fat versus control diets (RR 0.79, p=0.47; I(2)=0%), (RR 0.93, p=0.66; I(2)=0%), (RR 0.93, p=0.71; I(2)=57%) and (RR 1.18, p=0.26; I(2)=18%). The multivariate and univariate model showed no significant associations between the independent variables and the changes from saturated fat, monounsaturated fat, polyunsaturated fat and linoleic acid. Sensitivity analyses did not reveal a significant risk reduction for any outcome parameter when polyunsaturated fat was increased in exchange for saturated fat.The present systematic review provides no evidence (moderate quality evidence) for the beneficial effects of reduced/modified fat diets in the secondary prevention of coronary heart disease. Recommending higher intakes of polyunsaturated fatty acids in replacement of saturated fatty acids was not associated with risk reduction.

Project description:ObjectiveTo 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.DesignThe 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.SettingOne nursing home and six state mental hospitals in Minnesota, United States.ParticipantsUnpublished 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.InterventionsSerum 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 measuresDeath from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy.ResultsThe 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).ConclusionsAvailable 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.

Project description:Coronary heart disease (CHD) is one of the leading causes of morbidity and mortality worldwide, and more efforts should be made to reduce the risk of cardiovascular events. This study aimed to investigate the impact of clinical pharmacist intervention on the prognosis of acute coronary syndrome (ACS) in Chinese patients with CHD. Two hundred and forty patients who had ACS were recruited. Participants were randomly assigned to the intervention group (n = 120) or the control group (n = 120). The intervention group received a medication assessment and education by the clinical pharmacist at discharge and telephone follow-ups at 1 week and 1 and 3 months after discharge. The control group received usual care. The primary outcomes of this study were the proportion of patients who had major adverse cardiovascular events (MACEs), including mortality, nonfatal myocardial infarction (MI), stroke, and unplanned cardiac-related rehospitalizations within 6 and 12 months after hospital discharge. Secondary outcome was self-reported medication adherence to evidence-based medications for CHD (antiplatelets, statins, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). Of 240 enrolled patients, 238 (98.3%) completed 6-month follow-up, and 235 (97.9%) completed 12-month follow-up. There were no significant differences between intervention and control groups in the percentages of patients who incurred MACEs within the 6-month follow-up (3.3% vs 7.6%, respectively, P = 0.145) or 12-month follow-up (10.9% vs 12.1%, respectively, P = 0.783). Significant improvements were found in the prescribing rates of β-blockers and all four classes of medications at discharge in the intervention group compared with the control group (P = 0.001 and P = 0.009, respectively). There was no significant difference between the intervention and control groups in the use of all four classes of medications at the 6-month follow-up (48.3% vs 45.8%, respectively, P = 0.691) and 12-month follow-up (47.9% vs 46.6%, respectively, P = 0.836). The use of β-blockers was nonsignificantly higher in the intervention group than in the control group at the 6-month follow-up (74.2% vs. 64.4%, P = 0.103) and 12-month follow-up (74.8% vs 63.8%, P = 0.068). Clinical pharmacist intervention had no significant effects on reduction in cardiovascular events among patients with CHD. Further studies with larger sample sizes and longer time frames for both intervention and follow-up are needed to validate the role of the clinical pharmacist in the morbidity and mortality of CHD. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR-IOR-16007716.