Many people report unpleasant side effects while on statin drugs prescribed to lower their cholesterol. Some of the most common are digestive problems and muscle pain or weakness. But other more serious side effects can occur and this discovery led to a warning label requirement by the FDA in 2013, acknowledging increased risk of liver and kidney damage, type 2 diabetes, and memory loss, just to name a few.
More recently, research has uncovered other concerning findings regarding the effects of statin drugs on the immune system and heart disease risk factors. These newer findings are especially concerning considering that immune suppression and changes to coronary artery calcification (CAC) are both processes that can occur gradually and quietly, unbeknownst to the patient.
Increased Risk of Shingles
A study published last year in the British Journal of Dermatology was consistent with previous findings linking statin use with the occurrence of herpes zoster (HZ), commonly known as shingles. Caused by the reactivation of latent varicella zoster virus, HZ can be extremely painful and can result in lingering nerve pain (postherpetic neuralgia) for many years after infection. This large, matched, case-control study found a significantly increased risk of HZ in statin users and the risk appeared to be dose-dependent. Additionally, the risk of HZ occurrence decreased the longer a participant was off the statin. The pattern of these findings are typically indicative of a causal relationship, not just a correlative one.
Although exact mechanisms are unclear, it is thought that statin drugs suppress T-cell activation and proliferation. T-cells are involved in cell-mediated immunity, which is the part of the immune system that does not involve antibodies. Since HZ is thought to occur when cell-mediated immunity becomes compromised, this theory makes physiological sense. Because statin drugs are so widely prescribed (an estimated 25% of middle-aged adults are taking a statin), any negative side effects or outcomes could result in large public health implications. Herpes zoster greatly affects patients’ quality of life and treatment for postherpetic neuralgia is expensive, which has an impact on healthcare costs.
Changes in Atherosclerotic Plaque
While statins have long been thought to reduce the risk of cardiac events by decreasing total and LDL or “bad” cholesterol, several studies over the past few years have investigated statin-induced changes in atherosclerotic plaque. The findings are opposite of what you would think, raising controversy and weakening confidence in this classification of drugs among patients and healthcare providers alike. In an article published in Diabetes Care in 2012, the authors concluded that the progression of coronary artery calcification was significantly higher in type 2 diabetics who used statins more frequently compared with those who did not use statins or who used them more infrequently. Surprisingly, this occurred in spite of the participants’ well-controlled LDL cholesterol levels (those considered in normal range). Coronary artery calcification is associated with higher morbidity and mortality rates (due to cardiovascular disease) among this population. Other studies with similar findings were criticized because baseline CAC was not accounted for; but in this study, there was no difference between statin users and non-statin users at baseline. This same study also found no improvement of abdominal aortic artery calcification (AAC) in non-diabetics with no history of cardiovascular disease who were placed on statins. There was even progression of AAC in some participants.
Another study, published in Atherosclerosis in recent years, had similar findings and employed a newer non-invasive imaging technique called coronary computed tomographic angiography (CCTA), which is even more sensitive than coronary artery calcium scoring. In this study, the researchers found a strong association between statin use and coronary artery plaque features. Findings included higher frequency of severe coronary artery stenosis, more coronary vessels with obstructive cardiovascular disease, and more prevalent and extensive calcified and mixed (but not non-calcified) plaque. More research needs to be done to determine the clinical relevance of these findings, as another recent study confirmed them, but also showed no increased in heart-related events. But one thing is clear – worsening of coronary artery calcification was never an intention of statin drug treatment and the discovery of this process taking place as a result of a commonly prescribed drug is alarming and should be taken seriously until we know more.
Do You Really Need a Statin?
When taken as a whole, the research on statin drugs is conflicting. However, when you take a closer look at risk/benefit analysis and interpret the statistics based on absolute risk rather than relative risk, the evidence – or lack thereof – for the wide use of statins becomes less conflicting and more clear….and concerning. In fact, those at high risk for suffering a cardiac event (such as those with previous history of one), may in fact be the only population for whom the benefits clearly outweigh the risks. A growing body of research suggests that cholesterol levels may be a much weaker predictor of heart disease in the first place. Inflammation and homocysteine levels have become additional markers of interest in recent years as it pertains to heart health and can be measured through blood testing. It may be worth it to your health to investigate these other markers in addition to cholesterol. And if cholesterol levels are still a concern, the addition of dietary strategies, exercise, and dietary supplements can often to be enough to safely get them into healthier ranges.