"Recovered" unpublished data reveals that lowering cholesterol levels increase the risk of death by 22%

This study was published in the BMJ 2016 Apr 12;353:i1246

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

Ramsden CE, Zamora D, Majchrzak-Hong S, Faurot KR, Broste SK, Frantz RP, Davis JM, Ringel A, Suchindran CM, Hibbeln JR.
USA Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, University of North Carolina, Chapel Hill, NC, USA Chris.Ramsden@nih.gov.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/27071971

The objective of this study was to review the findings (by analysing unpublished "recovered" data from the original study investigators) of the Minnesota Coronary Experiment. The Minnesota Coronary Experiment was a double blinded, parallel group, randomized controlled dietary intervention trial conducted between 1968 - 1973, and was to designed to prove that increasing the polyunsaturated fat, (linoleic acid), and decreasing saturated fat in the diet would reduce cardiovascular events and deaths. It was the largest (9,570 participants, aged 20-97 years) and perhaps the most rigorously executed dietary trial of cholesterol lowering by replacement of saturated fat with vegetable oil rich in linoleic acid.

In the study participants were recruited from mental hospitals or nursing homes in the Minnesota area. They were divided into two groups:
(1) The intervention diet group had their dietary saturated fat cut in half (from 18.5% to 9.2% of calories) and their polyunsaturated linoleic fat intake massively increased from 3.4% to 13.2% of calories (a 280% increase).
(2) The control diet group did not change their saturated fat intake but did increase polyunsaturated linoleic acid intake from 3.4% to 4.7% of calories.

The "recovered" data, included previously unpublished records of serum cholesterol and autopsy reports and an extensive collection of study documents.

Using the "recovered" data the study found:
(i) The intervention group had significant reduction in cholesterol levels of 13.8%.
(ii) The control group had a small reduction in cholesterol levels of 1%.
(iii) A 30 mg/dL (0.78 mmol/L) decrease in cholesterol levels was associated with 22% higher risk of death from any cause.
(iv) Autopsy reports showed that participants in the intervention diet group had a 90% increased risk of a heart attack compared to participants in the control diet group. 

The researchers also did a systematic review of the scientific literature and identified five randomized controlled trials that provided vegetable oil(s) rich in linoleic acid in place of saturated fat. These five trials included 10,808 participants. The average change in cholesterol levels in the course of the randomized controlled trials ranged from 7.8% to 13.8% lower in the intervention versus control groups.

The review of the five trials found:
(v) Those in the (low cholesterol) intervention groups had a 13% increased risk of death from coronary heart disease compared to those in the higher cholesterol control groups.
(vi) Those in the (low cholesterol) intervention groups had a 7% increased risk of death from all causes compared to those in the higher cholesterol control groups. 

The above investigators also "recovered" unpublished data from the Sydney Diet Heart Study (1966-73) where the results of the trial was not fully reported. Ramsden commented: "Our recovery and 2013 publication of previously unpublished data from the Sydney Diet Heart Study (SDHS, 1966-73) belatedly showed that replacement of saturated fat with vegetable oil rich in linoleic acid significantly increased the risks of death from coronary heart disease and all causes, despite lowering serum cholesterol."

Critical points arise from this study:
(1) Key findings from landmark randomized controlled trials including the Sydney Diet Heart Study and the Minnesota Coronary Experiment were not fully published.
(2) Participants who had greater reductions in cholesterol levels had a higher, rather than lower, risk of death.

The question must be asked: "Why did the original investigators suppress this information?"

Is it because the results of the studies were clearly at odds with their beliefs?

Ramsden concluded: "It is interesting to speculate whether complete publication of randomized controlled trial results might have altered key policy decisions promoting replacement of saturated fat with linoleic acid rich oils (such as the 1977 McGovern report and National Cholesterol Education Program (1984-85) or contributed to a shift in research priorities."
  

High LDL cholesterol levels associated with a 15% reduction in hospital death rates in heart attack patients

This study was published in the American Journal of Cardiology 2015 Mar 1;115(5):557-62

Study title and authors:
Relationship between serum low-density lipoprotein cholesterol and in-hospital mortality following acute myocardial infarction (the lipid paradox).

Reddy VS, Bui QT, Jacobs JR, Begelman SM, Miller DP, French WJ; Investigators of National Registry of Myocardial Infarction (NRMI) 4b–5.
F. Hoffmann-La Roche, Basel, Switzerland. Electronic address: reddy.vanessa@gene.com

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25727079

This study investigated the association between cholesterol levels and in-hospital death rates in patients hospitalized for a heart attack. The study included 115,492 patients.

The study found:
(i) Patients with the highest LDL cholesterol levels had a 15% reduced risk of dying in hospital compared to patients with the lowest LDL cholesterol levels.
(ii) Patients with the lowest HDL cholesterol levels had a 20% increased risk of dying in hospital compared to patients with the highest HDL cholesterol levels.

Reddy concluded: "Lower LDL cholesterol levels associated with increased risk of in-hospital mortality".

Low levels of LDL cholesterol associated with a 65% increased risk of death in heart attack patients

This study was published in Critical Care Medicine 2015 Jun;43(6):1255-64

Study title and authors:
Lipid paradox in acute myocardial infarction-the association with 30-day in-hospital mortality.

Cheng KH, Chu CS, Lin TH, Lee KT, Sheu SH, Lai WT.
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25738856

The Killip classification (four classes - I to IV) is a system used in individuals with a heart attack. Individuals with a low Killip class are less likely to die within the first 30 days after their heart attack than individuals with a high Killip class.

This study was designed to clarify the relationship between cholesterol levels, Killip classification, and 30-day mortality in patients with a heart attack. The study included 724 heart attack patients.

The study found:
(a) Low-density lipoprotein (LDL) cholesterol and triglyceride levels were significantly lower in high-Killip (III + IV) patients compared with low-Killip (I + II) patients.
(b) Patients with low-density lipoprotein (LDL) cholesterol less than 62.5 mg/dL (1.6 mmol/L) had a 65% increased risk of death compared with patients with patients with low-density lipoprotein (LDL) cholesterol more than 62.5 mg/dL (1.6 mmol/L).
(c) Patients with triglyceride levels less than 110 mg/dL (1.24 mmol/L) had a 405% increased risk of death compared with patients with patients with triglyceride levels more than 110 mg/dL (1.24 mmol/L).
(d) Patients with a high-Killip classification and with with triglycerides less than 62.5 mg/dL (1.6 mmol/L) and low-density lipoprotein (LDL) cholesterol less than 110 mg/dL (1.24 mmol/L) had a 10.9-fold higher risk of death than patients with a low-Killip classification with triglycerides greater than 62.5 mg/dL (1.6 mmol/L) and low-density lipoprotein (LDL) cholesterol greater than 110 mg/dL (1.24 mmol/L).

Cheng concluded: "Low low-density lipoprotein (LDL) cholesterol, low triglycerides, and high Killip severity were associated with significantly higher 30-day in-hospital mortality in patients presenting with acute myocardial infarction".

Low cholesterol increases the risk of death by 75% after a heart attack

This study was published in the European Heart Journal 2001 Nov;22(22):2085-103

 

Study title and authors:

Assessment of absolute risk of death after myocardial infarction by use of multiple-risk-factor assessment equations: GISSI-Prevenzione mortality risk chart.

Marchioli R, Avanzini F, Barzi F, Chieffo C, Di Castelnuovo A, Franzosi MG, Geraci E, Maggioni AP, Marfisi RM, Mininni N, Nicolosi GL, Santini M, Schweiger C, Tavazzi L, Tognoni G, Valagussa F; GISSI-Prevenzione Investigators.

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI), Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Italy.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/11686666

This study investigated the risk factors for death in patients after they had suffered a heart attack. The study included 11,324 men and women from the GISSI-Prevenzione trial who were followed for four years.

Regarding cholesterol levels, the study found that those with the lowest cholesterol, under 190 mg/dL (4.91 mmol/L), had a 75% increased risk of death compared to those with the highest cholesterol, over 245 mg/dL (6.3 mmol/L).