Cardiovascular Disease Prevention and a Case for Statins
My grandfather died of his second stroke in 1990 at the age of seventy when I was eight. His first stroke occurred 9 years prior in 1981 at the age of 61. After his stroke, his right side was weak and both eating and walking were more challenging as a result. From what I have learned, he did not have atrial fibrillation (a condition that predisposes to stroke), he never smoked, and he rarely drank alcohol. Notably, most of his 8 brothers died of strokes or heart attacks by their 70th birthday. Despite this family history, my father and his five siblings are still alive in their 70s with only the oldest having required coronary artery disease intervention with a CABG (coronary artery bypass grafting). From my perspective, this is a good example of how cardiovascular disease (heart attack, coronary artery disease, stroke) management has changed in the last few decades and the resultant decline or at least delay in the onset of these conditions.
Several factors have contributed to the decline in cardiovascular disease and death. In the 1960s, a Surgeon General’s report came out linking smoking with heart attack and stroke, noting smokers had twice the risk of dying from heart disease in their lifetime compared to nonsmokers. In the 1970s, more emphasis was placed on improved blood pressure control. In the 1980s, the medical community had a better understanding of cholesterol risk factors and by September of 1987, the first statin was FDA approved. From 1980-2000, treatment after a heart attack evolved and included procedural interventions such as angioplasty and stenting. (1,2) In 1995, tPA (tissue plasminogen activator) was FDA approved to help break up clots in the acute treatment of stroke. In the span of four decades, the medical community developed multiple incredible tools for managing and preventing cardiovascular disease.
As internists, we feel very comfortable managing cardiovascular disease as we spend a lot of our training caring for patients in these acute situations, but what we love as primary care physicians is prevention. If we can help our patients manage risk factors well, our patients live healthier longer lives. Thus, we spend a fair amount of time discussing things like smoking cessation, blood pressure and cholesterol management, and treatment or prevention of diabetes. When we talk with patients about risk factors, we understand it is difficult to imagine taking a medicine when you feel fine and there is no current damage.
Most patients are understanding of blood pressure management as they see the elevated blood pressure readings in the clinic or at home with their blood pressure cuff. Cholesterol management, however, is often a more challenging conversation and this conversation has expanded to more people in the last 10 years due to a change in guidelines. We would previously advise a statin medication based on the LDL (bad cholesterol) number and we would target a goal LDL number based on patient risk factors. This felt more discrete and made sense to target the lab numbers. Nowadays, however, we advise a statin medication not just for an elevated LDL but also when the risk for heart disease over the next 10 years is elevated. Elevated risk populations would include patients with an LDL greater than 190, patients with diabetes, or patients with a 10 year risk of cardiovascular disease of 7.5% or greater. This risk calculation utilizes the patient’s age, gender, blood pressure, cholesterol numbers, smoking status, and presence or absence of diabetes. Of note, this does not take into account family history of heart attack or stroke (which matters!). You can check out your own risk score here -https://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calulate/estimator/. This change in treating patients based on risk rather than a number comes from the data that 40% of patients with coronary heart disease have a total cholesterol of less than 200 (normal) (3).
Statins remain the primary medication we use to lower LDL and cardiovascular disease risk because they are so well studied and effective. Meta-analyses of randomized, controlled trials have reported that for every reduction of 39 mg/dL of LDL, statins confer relative reductions in cardiovascular events and all-cause mortality of 22% and 10% respectively (3,4). We have learned that statins not only lower LDL but also appear to have a stabilizing effect on plaques that are already present in the arteries. Preventing plaque rupture and travel is an additional way to prevent a heart attack or stroke.
As patients hit 60yo, the risk for stroke and heart attack increases because cardiovascular disease is still the leading cause of death in the US (cancer being a close second). I was not surprised to see 2021 data from GoodRx showing atorvastatin was the most prescribed prescription medication in the US. While it is a commonly used medication and there are clear benefits of statins, we are noticing more statin reluctance. We understand that statin medications, as with all medications (supplements included), can have side effects. Most notably, patients raise concern about the risk for muscle aches. When this has been evaluated in studies, the risk for muscle pain has not been noted to be a significant increase from placebo. A meta-analysis of 130,000 people from 2017 showed 13.3% of subjects receiving a statin discontinued the drug compared with 13.9% of subjects on placebo over a mean follow up of 4.1 years (5). Of course, clinically we certainly see patients who struggle with muscle pains and often we can make modifications by decreasing the dose or potency of the statin or trying every other day dosing. The reason, however, that we are so supportive of statins over other cardiovascular disease prevention medications (fish oil, fibrates, niacin) is that in trials, these other medications have NOT clearly shown effectiveness in decreasing heart attacks, stroke, or death.
We understand there is the occasional patient who really does not tolerate statin medications well and thankfully more tools are coming to manage cholesterol and plaque formation. Ezetimibe is often used as an adjunct to statins and PCSK9 injectable medications are showing great promise especially for those who do not tolerate statins. However, these newer PCSK9 medications are still quite expensive and can be challenging for patients to access so statins remain our most powerful and accessible tool.
Dr. Connolly and myself try to avoid medications when we can and both a healthy diet and lifestyle are still important aspects in preventing cardiovascular disease. We have certainly seen patients make great strides in their cholesterol numbers with dietary changes but there are many who have a genetic component that makes significant lowering of the LDL with diet challenging. When we discuss your risk factors and these preventative medications, we hope you know that it comes from our desire to keep you happy and healthy longer. I realize there are many factors at play here, but my father has already outlived my grandfather and I’m so thankful to have him around.
References:
1. Weir HK, Anderson RN, Coleman King SM, Soman A, Thompson TD, Hong Y, et al. Heart Disease and Cancer Deaths — Trends and Projections in the United States, 1969–2020. Prev Chronic Dis 2016;13:160211. DOI: http://dx.doi.org/10.5888/pcd13.160211external icon.
2. Javaid Iqbal, Julian Gunn, Patrick W. Serruys, Coronary stents: historical development, current status and future directions, British Medical Bulletin, Volume 106, Issue 1, June 2013, Pages 193–211, https://doi.org/10.1093/bmb/ldt009K
3. Minchos, ED, McEvoy JW, Blumenthal RS. Lipid Management for the Prevention of Atherosclerotic Cardiovascular Disease. Review Article. New England Journal of Medicine. 2019;381:1557-67.
4. Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and Lipid Management to Prevent Atherosclerotic Cardiovascular Disease and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: a systematic review and meta-analysis. JAMA 2016; 316: 1289-97
5. Khan RH, et al. Meta-analysis of Placebo-Controlled Randomized Controlled Trials on the Prevalence of Statin Intolerance. Am J Cardiol. 2017;120(5):774. Epub 2017 Jun 13.
