Statins worsen heart function in 71% of patients

This study was published in the American Journal of Cardiology 2004 Nov 15;94(10):1306-10

 

Study title and authors:

Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction.

Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.

Heart Failure Institute, Department of Medicine, Advocate Christ Medical Center, University of Illinois/Christ Cardiovascular Disease Fellowship Program, Oak Lawn, Illinois 60453, USA. marc.silver@advocatehealth.com

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15541254

This study evaluated left ventricular diastolic function before and after statin therapy. The study included 14 patients (who met the National cholesterol Education Program's recommendations for initiating pharmacologic therapy), aged 51 - 79 years, who completed three to six months on atorvastatin.

The study found that 71% of the patients had worsening of left ventricular diastolic function after taking statins.

Dr Silver concluded: "For more than a decade, there has been a suggestion of impairment of diastolic function after the administration of statins, and our findings suggest that this may be a common event and potentially a precursor to symptoms associated with ventricular dysfunction".

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).

Possible mechanisms of how statins cause diabetes

This paper was published in Metabolism 2014 Feb 25

Study title and authors:
Statin treatment and new-onset diabetes: A review of proposed mechanisms.

Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS
Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24641882

Brault notes that new-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. Brault discusses the mechanisms that may be involved between statins and diabetes.

(a) Statins affect insulin secretion through direct, indirect or combined effects on calcium channels in pancreatic β-cells.
(b) Statins reduce the expression of glucose transporter 4 (GLUT 4). GLUT 4 is a protein that transports glucose from the bloodstream into cells. Reduced GLUT 4 in response to statins results in hyperglycemia (high blood sugar) and hyperinsulinemia (excess levels of insulin in the blood).
(c) Statin therapy decreases other important molecules such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling.
(d) Statins interference with intracellular insulin signaling pathways via inhibition of necessary phosphorylation events (phosphorylation influences protein enzymes) and reduction of small GTPase action (GTPases are key proteins in many critical biological processes such as hormonal and sensory signals, and the protein building ribosomes). 
(e) Statins can decrease levels of peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which regulate glucose levels.
(f) Statins may also diminish levels of leptin and adiponectin which also play a role in regulating glucose levels.

Statins use is associated with increased HbA1c levels in patients with high blood pressure

This study was published in Diabetology and Metabolic Syndrome 2014 Apr 23;6:53

Study title and authors:
Statins use is associated with poorer glycaemic control in a cohort of hypertensive patients with diabetes and without diabetes.

Liew SM, Lee PY, Hanafi NS, Ng CJ, Wong SS, Chia YC, Lai PS, Zaidi NF, Khoo EM
Department of Primary Care Medicine, University of Malaya Primary Care Research Group (UMPCRG), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24782916

This study sought to determine the association between the use of statins and glycaemic control in patients with high blood pressure. The study included 1,060 patients.

The study found:
(a) Analysis of the whole group found that statin users had 29% higher HbA1c levels than statin non users.
(b) Analysis of those with diabetes found that statin users had 20.8% higher HbA1c levels than statin non users.

Liew concluded: "Statins use is associated with increased HbA1c levels among hypertensive patients and hypertensive patients with diabetes".

Professor concludes that results from statin trials may be considerably flawed

This paper was published in the British Medical Journal 2 May 2014

Study title and author:
Meta-analysis of side effects of statins shows need for trial transparency
Joan-Ramon Laporte
Professor of Clinical Pharmacology Montserrat Bosch

Universitat Autònoma de Barcelona, P Vall d'Hebron 129-139 08035 Barcelona

This paper can be accessed at: http://www.bmj.com/content/348/bmj.g2940/rr/696651

This article, authored by Professor Joan-Ramon Laporte from the Autonomous University of Barcelona noted the exclusions in statin clinical trials.

Professor Laporte found:
(a) In the HPS (Heart Protection Study), 32,145 patients with the inclusion criteria participated in a run in phase, but 11,609 (36%) were excluded because of lack of effect on cholesterol, increase in liver enzymes, increase in CPK, or increase of creatinine, or also because "the patient had little probability of complying with the treatment during 5 years".
(b) In the MEGA trial (Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese), 15,210 patients entered a 4-week run in phase, but 7,201 (48%) were excluded for similar reasons, and only 8,009 finally participated in the trial.
(c) In the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), 89,890 were initially screened, but 78% were excluded for unclear reasons, and only 19,323 were considered for randomisation. Then, an additional 1,521 were excluded during a run in phase because of poor treatment adherence, and only 17,802 patients (19.8%) were finally randomised.

Professor Laporte concluded that in view of these massive exclusions, the data from these trials may be considerably flawed and lacked validity, and that no conclusions could be drawn from the results of the trials.