Statins associated with increased risk of death in those with heart failure

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From a purely physiological perspective, the heart is essentially a bag of muscle that pumps blood around the body. In certain circumstances, the heart’s pumping action can weaken, ultimately resulting in what is usually termed ‘heart failure’. Symptoms of this can include fatigue, breathlessness and fluid retention.

I was interested in a study recently published in the journal Cardiology that assessed the relationship between LDL-cholesterol levels and health outcomes in a group of 212 elderly individuals with known heart failure [1]. These individuals were split into 3 groups according to their LDL-cholesterol levels.

1.    < 90 mg/dl
2.    90-115 mg/dl (2.3-3.0 mmol/l)
3.    >115 mg/dl

Over an average of 3.7 years, the individuals in the 1st group (with then lowest LDL levels) fared worst. Those in group 3 (with the highest LDL levels) fared the best. 58 per cent of people in group 3 lived at least 50 months compared to just 34 per cent in group 1. These results were in spite of the fact that at the start of the study this group had a disproportionate number of people with severe heart failure in it.

Some argue that any relationship between low cholesterol and worsened health outcomes is most likely due to the fact that long-standing illness can lead to weight loss from poor nutritional status, and that cholesterol levels fall as a result. In other words, it’s poor health that is causing lower cholesterol levels, not the other way round.

However, in this study, the subjects started out with what appeared to be broadly identical nutritional status, which suggests that the explanation above is not valid here. According to the authors, “LDL-[cholesterol] may be considered an independent predictor of mortality.”

Why might low LDL-cholesterol levels be a risk factor for mortality? The authors point out that cholesterol can alter the functioning of certain inflammatory substances (including C-reactive protein and cytokines), and therefore low-cholesterol might lead to a more inflammatory state (which is not healthy).

One very interesting thing about this study was that it found that mortality across the groups was no different in individuals not treated with statins. What this suggests is that statins might be having a direct effect that is harmful to the hearts and health of individuals with heart failure.

If I was to hazards a guess as to what this might be, I’d suggest it could have something to do with the fact that statins are known to have the capacity to deplete the body of the substance Coenzyme Q10. Statins reduce cholesterol by inhibiting an enzyme in the liver known as ‘HMG-CoA reductase’ which ‘drives’ cholesterol production. But HMG-CoA reductase also facilitates the production of coenzyme Q10, which itself participates in the production of what is known as ‘adenosine triphosphate’ (ATP) – the most basic unit of energy ‘fuel’ in the body. In other words, Coenzyme Q10 is critical to energy production in the heart muscle and therefore heart function.

Taking statins has been proven to have the capacity to lower levels of CoQ10 in the body [2]. A while back, I came across a review of the evidence for statin-inducted CoQ10 depletion in both humans and animals [3]. Here’s what its authors had to say in their concluding remarks:

Statin-induced CoQ10 deficiency is completely preventable with supplemental CoQ10 with no adverse impact on the cholesterol lowering or anti-inflammatory properties of the statin drugs. We are currently in the midst of a congestive heart failure epidemic in the United States, the cause or causes of which are unclear. As physicians, it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a wide-spread deficiency of a nutrient critically important for normal heart function.

And here’s the conclusion from the Cardiology study:

Low LDL-[cholesterol] levels are association with a reduced survival in elderly patients with clinically controlled moderate and severe [heart failure]. Statins were independently and significantly associated with a higher risk of mortality.

The underlying message here appears to be that in individuals with heart failure, statins are contraindicated. Some doctors may be aware of this, but others may need to be educated regarding this by their patients or patients’ carers.

References:

1. Charach G, et al. Low levels of low-density lipoprotein cholesterol: a negative predictor of survival in elderly patients with advanced heart failure. Cardiology 2014;127(1):45-50.

2. Passi S, et al. Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 2003;18(1-4):113-24.

3. Langsjoen PH, et al. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. Biofactors 2003;18(1-4):101-11.

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