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Statin and Exercise to Reduce the Risk for Cardiovascular Diseases

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Statin and Exercise to Reduce the Risk for Cardiovascular Diseases essay
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The human body is very complex in the physiological mechanisms it could sustain. The human physiology ranges from different mechanical, physical and biochemical functions of normal tissues or organs. The human body consists of many systems organs, tissues, cells that all play a role in the way it interacts with medications. Drugs, or a substance enter the body and alter the physiological mechanisms of the human body positively, but with the right intentions. The specific drug class of statins help to lower cholesterol levels in the blood.

This helps to lower the risk for heart disease such as heart attack, stroke, etc (Parker & Thompson, 2012). However, medications aren’t the only way to reduce the risk of cardiovascular disease, the healthiest way is to exercise. Exercise can benefit the individual positively and increases health in many different ways. What if we can use this drug class of statin and exercise to produce a greater effect? If this specific medication reduces the risk for cardiovascular diseases as well as exercise, can’t we do both?

Statins are prescribed by doctors to help lower cholesterol levels in the blood. Lowering levels of cholesterol helps to prevent heart attacks, stroke and other heart disease. Physical activity also reduces the risk of cardiovascular disease by reducing lipid profile, blood pressure, insulin resistance and obesity (Parker & Thompson. 2012). Taking this medicine while being physically active can further reduce the risk for CVD. There could be side effects to taking a statin while performing physical activity such as myalgia and creatine kinase elevation leading to soreness, cramping, spasm, etc (Parker & Thompson, 2012). Although there could be side effects, the combination of statins and exercise could reduce risk for CVD at a greater effect.

However, there are risks depending on the individual. The level of intensity at which the individual is exercising at while taking statins could determine the amount myalgia he/she would go through (Deichmann et al., 2015). Depending on the individual’s fitness level and intensity leads to a different effect. In that case, each individual would be prescribed a different exercise routine as well as different dosage of the statin medication. Overall, there should be careful attention to identifying high-risk from low-risk groups and strategies to prevent side effects (Deichmann et al., 2015).

Cholesterol is produced by the liver and transported by lipoproteins which consist of two types, low density lipoprotein LDL, known as the bad fat, and high density lipoprotein HDL, known as the good fat. LDL’s main function is to transport cholesterol throughout the body, while HDL removes excess cholesterol and carries it back to the liver for degradation. Statins or 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase inhibitors work by competitively inhibiting the conversion of HMG coenzyme A to mevalonate by blocking the HMG coenzyme reductase receptor, which is the rate limiting step in cholesterol biosynthesis (Deichmann et al., 2015).

Presence of a statin in the binding pocket of the enzyme blocking HMG coenzyme A substrate will inhibit both mevalonic acid and cholesterol synthesis. Inhibition of this enzyme also decreases cholesterol synthesis leading to an upregulation in LDL receptors in the liver (Deichmann et al., 2015). This increases LDL uptake by the hepatocytes decreasing the amount of LDL cholesterol in the blood. Mevalonic acid is associated with the production of ubiquinone (coenzyme Q10). Therefore, inhibition of mevalonic acid results in lower ubiquinone levels as well as the reduction in dolichols and isoprenylated proteins that are involved in cellular respiration and muscle cell functioning (Deichmann et al., 2015).

According to the American college of Cardiology, statins are given as a prevention of cardiovascular disease in patients with LDL cholesterol more than 190mg/dl. On average statins can lower LDL by 70mg/dl which translates into an estimated 60% decrease in the number of cardiac events life heart attacks or sudden cardiac events. Contraindications of statins, being drugs that are metabolized and excreted by the liver could lead to chronic liver disease or elevation of serum transaminases. Also, monitoring creatine kinase is important in patients taking statin as myopathy is one of the most common and dangerous adverse effect of this class of medications (Deichmann et al., 2015).

Myalgia is a muscle discomfort/weakness resulting in a sensation of pain, soreness, cramping, spasm or achiness with or without an elevation in creatine kinase levels. Myositis or muscle inflammation could occur with elevated CK levels (Taylor et al., 2014). Statin associated myopathy occur from reduction in myocyte cholesterol levels required for sarcolemma, sarcoplasmic reticulum, and T-tubule stability. Without the presence of cholesterol, these structures become defective. Statins inhibit CoQ10 production because this protein relies on LDLs and VLDL to transport it (Taylor et al., 2014).

However, since statins lead to a decrease in LDL concentration, CoQ10 levels will decrease as well. Normal mitochondrial respiration requires a mitochondrial transport protein, CoQ10. Statin therapy results in a substantial risk of mitochondrial diseases associated with decreased CoQ10 production (Taylor et al., 2014). Muscle diseases associated with statin myopathies include myasthenia gravis, McArdle disease, amyotrophic lateral sclerosis, myotonic dystrophy, muscular dystrophy and motor neuropathies (Deichmann et al., 2015).

Regarding my hypothesis, I would think that using statins and exercising can produce a greater effect slowly but surely. However, to a certain extent because all medications can have different side effects to the body. If an individual is performing physical activity at a moderate intensity on a daily basis while taking this medicine, would have a positive outcome. However, I believe that the higher intensity you perform on a daily basis, such like athletes, would not be the best idea to take this class of statins. Statins can negatively affect the athlete’s performance because of the interaction of the substance with muscle contraction. Overall, I think that statins could lead to muscle fatigue faster because its preventing muscles from working correctly and efficiently (Deichmann et al., 2015).

A study was done on hypercholesterolemic mice to determine if acute and chronic exercise can influence statin-induced myopathy. Mice either received daily injections of saline or simvastatin divided into three groups. One group remained sedentary, second engaged in daily exercise for two weeks and third engaged in daily exercise for two weeks after a period of training (Chung et al., 2016).

This study resulted with impaired muscle function within the group engaging in exercise and receiving statin treatment, presented by decreased running wheel activity, grip strength and maximal isometric force. Normally, exercise increases mitochondrial content and myofiber size while decreasing 4-HNE (Chung et al., 2016). However, the statin treatment prevented this from occurring and the mice were not able to reach those beneficial adaptations.

Overall, short term exercise does not worsen statin-induced myopathy however, statin treatment prevents muscle from building an adaptive response to training and subsequently decrease performance (Chung et al., 2016). Exercise groups compared to sedentary show increased systemic inflammation and atrogin-1 mRNA which could lead to myopathy overtime. Although short term exercise didn’t have any major statin-induced myopathy, however long-term exercise could (Chung et al., 2016).

Another study was done with 4460 amateur runners where injury is common to occur. Runners were divided between statin users, non-statin users with hypercholesterolemia and a control group (Bakker et al., 2017). Their original data of muscle injuries within amateur runners was compared with the statin treatment data after performing the study and showed no difference in injuries.

In conclusion, statins use did not increase injury risk in amateur runners. However, since this was a study with a smaller sample size and used on individuals who aren’t highly active or athletes could be the reason why (Bakker et al., 2017). For example, a large American study was done on active-duty soldiers and reported an increased risk of muscle injury with the treatment of statins with a follow up of 5 years. This concludes that short term exercise is not likely to result in muscle injury with the treatment of statins, but long term is likely (Bakker et al., 2017).

Lastly, a big study was conducted on 2,331 patients with chronic heart failure and 58% of those patients are prescribed with statins. There wasn’t any evidence found to prove that statin treatment impairs exercise training of CHF patients within 3 months (Kelly et al., 2016). Similar studies also presented the same findings. Patients who are also taking statin therapies for 6 months had their symptoms, muscle strength, and exercise capacities evaluated.

Resulting with no decrease in capacities and without demonstrating a decreased response to exercise training. Although this is a much bigger study and it did not show any evidence of injury within a long-term period (Kelly et al., 2016). However I would assume that these patients performed moderate/minimum activity compared to the studies mentioned previously with the soldiers where they are performing a higher intensity activity compared to patients with CHF.

My original hypothesis was that individuals performing moderate intensity activity will not result in any type of statin-induced myopathy whereas, vigorous activity will result in some sort of myopathy. The first study with the mice proved that vigorous exercise lead to muscle impaired function but not any myopathy in a short period, supporting my hypothesis.

To compare the studies where moderate and vigorous intensity took place does show a difference in results. A study with CHF patients and a study with soldiers definitely presented a difference where CHF patients didn’t result in any muscle impairment where the soldiers did. The soldiers are active duty individuals that perform a big number of activity and were monitored for 5 years. Resulting in an increased risk of injury with statin treatment supporting that long-term vigorous exercise leads to statin induced myopathy.

On the other hand, CHF patients are probably performing moderate activity since they are going through a symptomatic disease therefore supporting that moderate activity does not lead to loss muscle function. To go along with that a study was done on 22 professional athletes with familial hypercholesterolemia and all were treated with statins. They were monitored for 8 years to find out that about 80% of the athletes don’t tolerate statin treatment (Sinzinger & O’Grady 2004).

Overall, from these studies I can conclude that short term moderate/minimal exercise with statin treatment won’t have any effects but could lead to muscle impairment that could decrease activity. On the other hand, long term moderate/minimal exercise could lead to statin induced myopathy overtime. Similarly, short term vigorous exercise won’t have any effects but does have a higher chance of resulting in muscle impairment. On the other hand, long term vigorous activity has a higher chance of resulting in statin induced myopathy overtime.

References:

  1. Parker, B. A., & Thompson, P. D. (2012). Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exercise and Sport Sciences Reviews,40(4), 188–194. http://doi.org/10.1097/JES.0b013e31826c169e
  2. Deichmann, R. E., Lavie, C. J., Asher, T., DiNicolantonio, J. J., O’Keefe, J. H., & Thompson, P. D. (2015). The interaction between statins and exercise: mechanisms and strategies to counter the musculoskeletal side effects of this combination therapy. The Ochsner Journal,15(4), 429–437.
  3. Kelly, J. P., Dunning, A., Schulte, P. J., Fiuzat, M., Leifer, E. S., Fleg, J. L., … Mentz, R. J. (2016). Statins and exercise training response in heart failure patients insights from HF-ACTION.JACC. Heart Failure,4(8), 617–624. http://doi.org/10.1016/j.jchf.2016.05.006
  4. Chung, H. R., Vakil, M., Munroe, M., Parikh, A., Meador, B. M., Wu, P. T., … Boppart, M. D. (2016). The impact of exercise on statin-associated skeletal muscle myopathy. PLoS ONE,11(12), e0168065. http://doi.org/10.1371/journal.pone.0168065
  5. Sinzinger, H., & O’Grady, J. (2004). Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems. British journal of clinical pharmacology,57(4), 525-8.
  6. Taylor, B. A., Lorson, L., White, C. M., & Thompson, P. D. (2014). A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. Atherosclerosis,238(2), 329-35.
  7. Bakker, E. A., Timmers, S., Hopman, M., Thompson, P. D., Verbeek, A., & Eijsvogels, T. (2017). Association between statin use and prevalence of exercise-related injuries: a cross-sectional survey of amateur runners in the Netherlands. Sports medicine (Auckland, N.Z.), 47(9),1885-1892.

Statin and Exercise to Reduce the Risk for Cardiovascular Diseases essay

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FAQ

Do statins reduce cardiovascular events?
Compared with the control group, the statin group showed that statins can effectively reduce the risk of cardiovascular events (RR=0.77, 95% CI: 0.72~0.82, I 2 =0%), as shown in Figure 8. The occurrence of any cardiovascular events in included studies.
How do statins reduce the risk of cardiovascular disease?
Statins decrease your risk of having a stroke or heart attack because they cut down the amount of bad cholesterol in your blood . That cholesterol can make your arteries narrow (atherosclerosis), making it hard for your blood to circulate and putting you at risk for a heart attack or stroke.
How does statin affect exercise?
Despite the salutary effects, there are some unintended consequences of statins, including being linked to muscle pain, cramps, and fatigue, which may lead to reduced levels of physical activity (PA) and/or structured aerobic exercise .
Which type of exercise is most likely to reduce the risk of cardiovascular disease?
For those who want to lower the risk for heart attack and stroke, 40 minutes of moderate to vigorous intensity aerobic activity , 3 or 4 times a week, is recommended [116]. Moderate-intensity exercise is more widely performed among people who are interested in exercise and enjoy rest time.
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