Hypercholesterolemia in the Secondary Prevention of Coronary Heart Disease - Essay Example

?Hypercholesterolemia in Secondary Prevention of Coronary Heart Disease Introduction Figure Symptoms of CHD Coronary heart disease (CHD) is a condition in which the lumen of the coronary arteries (blood vessels that supply blood and oxygen to the heart) are narrowed down. In the developed world, it is one of the leading causes of death both in men and women. Around 94,000 deaths each year in the UK are attributed to this condition and the prevalence of this condition is about 2.6 million. The most common symptom associated with coronary heart disease (CHD) is angina and about 2 million people are affected with it each year. With age the prevalence and severity of CHD would only increase (NHS 2009). The two most notable conditions that are associated with CHD are angina and myocardial infarction. Myocardial infarction arises when coronary arteries are completely blocked and angina arises when the coronary arteries are partially blocked. Some of the common symptoms that are associated with CHD include breathlessness, chest pain, palpitations, a feeling of heaviness or tightness over the chest, sweating, confusions, anxiety, light-headedness, breathlessness, and dyspnea. Some of the common complications that can arise with the progression of CHD include heart attack, angina, heart failure, and arrhythmia (Mayo Clinic 2012). The main pathophysiology associated with CHD is the build-up of plaque in the coronary artery. As the plaque builds up, the lumen of the vessel becomes narrower, and so does the heart receive reduced supply of blood, resulting in the development of several symptoms of CHD including chest pain, breathlessness, and light-headedness. The process of development of this plaque may take long and often can go unnoticed, until more serious conditions such as heart attack develops. As mentioned earlier, the main cause of CHD is the narrowing down of the blood vessel lumen and often the inner vessel wall may suffer injury resulting in reduced supply of blood to the heart. A variety of risk factors may be associated with plaque-build-up and damage of the coronary artery vessel wall including smoking, hypertension, diabetes mellitus, radiation therapy and hypercholesterolemia. The inner vessel wall of the artery is damaged due to deposits of cholesterol and cellular wastes that cause a process of atherosclerosis of thickening of the vessel wall. Following the process of atherosclerosis, there may be breakage or rupture of the plaques resulting in deposition of platelets at the site of repair. This platelet clump may block the lumen resulting in partial or complete arterial blockage causing angina or myocardial infarction (Mayo Clinic 2012). Figure 2: Complications of CHD In the UK, the prevalence of hypercholesterolemia is high. About 1 in every 500 individuals is affected with familial hypercholesterolemia (an autosomal dominant condition characterised by high levels of Low Density lipoproteins (LDL) in the blood resulting in the development of atherosclerosis at a very rapid rate). Further the prevalence of hypercholesterolemia due to sedentary lifestyle, lack of exercises and diet has resulted in very high prevalence of CHD in the population. About 10 to 15% of the 110,000 population that have familial hypercholesterolemia are unaware of their condition, due to which they may be at a very high risk to suffer from angina or myocardial infarction (Wadwa 2007). Almost every patient with coronary artery disease has a minimum of one modifiable cardiovascular risk factor, and that most of the risk factors remain insufficiently controlled even after patients are diagnosed for Coronary Heart Disease (CHD). “Hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). The body needs this substance to build cell membranes, make certain hormones, and produce compounds that aid in fat digestion. Too much cholesterol, however, increases a person's risk of developing heart disease” (Hypercholesterolemia 2007). When the serum levels of cholesterol are elevated, the chances of being affected with CHD is increased by 50% in men by the age of 50, and by 30% by the age of 60 in women (NICE 2007). Figure 3: Risk Factors for CHD The secondary prevention of CHD is a very important realm of medicine as the disorder once recognised needs to be closely monitored and followed-up in order to reduce the risk of heart attack or stroke from developing. Besides, the quality of life would significantly improve. Some of the treatment measures that have been suggested include lifestyle changes (such as low-fat diet, tobacco cessation, weight management, and physical activity), treatment of hypertension and diabetes through lifestyle, diet and medication, surgery and control of lipid in the blood. In recent years, a lot of interest has been generated in the control of hypercholesterolemia and hyperlipidemia as it has been hypothesized reducing cholesterol levels in the blood can reduce the risk of development of cardiac events. The control of cholesterol would be made through lifestyle changes, diet control, and medications (such as statins). Control of hypercholesterolemia is said to reduce the chances of major cardiac events from occurring, promotes cardiac revascularisation and reduces the risk of cerebro-vascular events (such as stroke by 1%) (Hall 2010). In this paper, the various evidences would be studied in greater detail in order to get an idea of effective management of hypercholesterolemia in order to determine its effect on CHD. Literature Review A search was conducted across five databases namely, Pubmed, Cochrane, Google Scholar, BMJ and NEJM for articles related to hypercholesterolemia management in the secondary prevention of coronary heart disease. The search term “Hypercholesterolemia Management AND Coronary heart disease secondary prevention” was utilised along with certain limits/filters in order to obtain the relevant articles. The subject area chosen includes medical, nursing, cardiology and others. Both animal and human studies were included, no specific language was chosen, and included all age-groups and type of papers. The time period chosen was over the last 5 years. The Boolean operator used was ‘AND’. The total number of results obtained was about 206 articles, with an appropriate number obtained from Google Scholar, Pubmed and NEJM. The search met the criteria as the articles obtained were relevant to this study. From the 200+ articles that were obtained, 11 were hand selected to be included in this study, and the findings of these studies were considered in proving the hypothesis. No Question Results 1 Database searched: Pubmed, Google Scholar, Cochrane, BMJ and NEJM 2 Search Query/keywords: Hypercholesterolemia Management AND Coronary heart disease secondary prevention 3 Limits:-     a.      Abstracts / Full Texts All   b.       Subject Area Medical, Nursing, Others   c.      Humans / Animal Both   d.       Type of Paper All   e.      Language All   f.      Age/ Age-groups Nil   g.        Time period Last 5 years 4 Search Strings with the Boolean Operator Hypercholesterolemia Management AND Coronary heart disease secondary prevention 5 Results: Total articles retrieved 53 Articles from Pubmed; 105 Articles from Google Scholar; 1 Article from Cochrane; 19 Articles from BMJ; 28 Articles (Total of 206 Articles) 6 Did it meet the criteria? Yes Figure 4: Search Result Logistics The first study being selected was by Baigent et al (2008) in the Lancet concerning the efficacy and safety of LDL reducing treatment so as to reduce the prevalence of CHD and reduce the risk of major cardiac events. The study was a meta-analysis of more than 90,000 individuals from 14 trials from which statins were being used. From estimates conducted before this study, it was found that statins produced outcomes of reducing the LDL level by about 1 mmol/L. Of the 90,000 patients being studied during the 5-year period of the various trials, about 8000 died, 14000 developed major cardiovascular events, and 5000 developed cancers. As estimated, the mean LDL level fell by about 1 mmol/L (ranging from 0.35 to .177). For every 1 mmol/L, there was a reduction in mortality by about 12 %, and combining with stroke, major cardiac events, coronary revascularisation, myocardial infarction and coronary death, there was a drop by about 21% of these major events. The benefits of statins were significant during the first year, and during the following years, it was even greater. There was a drop of 48 patients per 1000 of those having pre-existing CHD every year once the LDL level was reduced by 0.20 mmol/L. However, in general it was found that statins did not increase the risk for cancer. Not much depended on the initial lipid profile. The second study conducted was by Ford et al (2007) and was an RCT wherein men with CHD were randomised into 2 groups, one which received pravastatin and the other which received a placebo and both were closely followed up for a 5 year duration. This was one of the few long term studies conducted to determine the effect of statin in the lowering of LDL in patients with CHD. All data was being tracked including hospitalisations, major cardiac events, death, stroke, cancer, etc. The risk of death from CHD was 10.3% in the placebo group and 8.6% in the statin group, over the 10 year period of the study. During the follow-up period, the death rate from CHD was 15.5% in the placebo group and 11.8% in the statin group. During the period of study and the follow-up, the death rate from CHD and other causes was reduced in the statin group, and there was no evidence of excess death from any other causes. Hence it has been suggested that 5 year treatment with Statins help to reduce cardiac mortality for 10 years in men having hypercholesterolemia, but not a history of myocardial infarction. Thus it can be said that the effect of statin is much efficient than a placebo. The third study was conducted by Paez and Allen (2006) to evaluate the cost-effectiveness by a nurse practitioner to control the lipid profile of patients with CHD in a managed care perspective, following cardiac revascularisation. More than 220 patients with hypercholesterolemia were included in this study during hospitalisation following cardiac revascularisation. The patients following cardiac revascularisation were divided into 2 groups. One group received feedback on the lifestyle changes needed, pharmacological intervention for 1 year and the usual care from the nurse practitioner (NURS). The other group received usual care along with feedback on lipid control (EUC) by the primary care giver or the cardiologist. In the year 2004, it was found that there was an incremental cost for the NURS, based on changes with the LDL level. There was a cost effective approach noted when nursing practitioners were utilised for a reduction in LDL. The nursing salaries required were lower to manage these cholesterol therapy regimes compared to the costs of salaries for cardiologists and other healthcare professionals. However, one finding noted was that since the nurses titrated the levels of statins required to a higher level in order achieve efficacy, the costs of drug therapy was slightly higher. However, in general in a managed care setup, nursing practitioners is a more cost-effective approach to manage and improve the care of patients with CHD. The fourth study selected was by Fuentes et al (2008) concerning an adjuvant that can be used to control the level of LDL Cholesterol in patients with CHD. The study was conducted on patients with familial hypercholesterolemia, which is associated with increased cardiac risks. This study was conducted to test the effect of plant sterols on LDL levels in the blood, endothelial functions and particle size of LDL. The study was conducing in a tertiary care ambulatory setting and 30 subjects were chosen with familial hypercholesterolemia. They were given low-fat along with consumption of sitosterol (a plant sterol) for duration of 4 weeks. The LDL particle size was analysed after the study period. It was found that the plasma sitosterol/cholesterol level was higher when the plant sterol was being consumed, than when not consumed. During the intake of plant sterol, there was a decrease in the LDL levels. It was found that the reduction in LDL levels was much greater when plant sterols were included in a low fat diet, rather than a low fat diet alone. Hence, the use of plant sterols as an adjuvant has been suggested in the secondary prevention of coronary heart disease to manage hypercholesterolemia. The fifth study selected was by Alves et al (2010) to differentiate between genetic and environmental dyslipidemia in the management of coronary heart disease. Patients with familial hypercholesterolemia have a higher risk to develop CHD. By using molecular methods it may be possible to identify the risk for CHD early in life and thus suggest appropriate lifestyle changes and therapeutic modifications. Using molecular methods, more than 400 patients were identified from 1000’s with familial hypercholesterolemia. These patients possessed a mutation in the LDLR Gene, and there was a distortion in the total cholesterol levels, LDL cholesterol levels and the ApoB levels. However, it was difficult to distinguish between patients having a mutation with the LDLR gene and those who did not have a mutation through lipid profile tests. Hence, performance of molecular diagnosis for LDLR gene has been suggested as a tool to identify hypercholesterolemia in patients with coronary heart disease early in life. The sixth study being examined is by Cziraky et al (2008), goes beyond mere LDL-reduction in managing hypercholesterolemia in patients with CHD. The study focuses on treating low HDL levels and high triglyceride levels even after managing the LDL levels appropriately through statin therapy. The authors noted that statins did not completely reduce the cardiovascular risk in patients with CHD. In diabetes, significant residual risk would still be present after lipid-lowering therapy. This may be from the low HDL levels and the high triglyceride levels that may still be persistent. When the HDL levels are increased it has been noted that the cardiovascular risk would reduce and the presence of high Triglyceride is associated with atherosclerosis. Besides, the cardiovascular risk would significantly reduce when HDL and triglyceride therapy is combined with LDL. Hence a combination therapy has been suggested at the national level for effective management of CHD. Niacin and fibrates are known to control several lipid parameters and reduce the cardiovascular risk significantly. Niacin is not only safe but also efficient. Besides, it slows down the process of atherosclerosis in cardiac patients. Niacin/simvastatin combination is suggested in CHD patients and also those who have co-existing diabetes. The costs effectiveness of combination is much better than simvastatin monotherapy as the risk for critical cardiac events are significantly reduced. The seventh study by Murphy et al (2009) analyses the effectiveness of a complex intervention strategy that includes customised patient management and the development of patient care plans in patients with CHD. More than 900 patients took part in this study and the interventions chosen included tailored care plans for practise and tailored care plans for patients. For practices the measures implemented were training for prescription and behaviour modification, provision of administrative support and frequent newsletters. For patients the measures implemented were goal identification, interviewing and target setting with relation to lifestyle modification. A few patients were placed in the control group. The three parameters compared between the intervention and the control groups were systolic blood pressure, diastolic blood pressure and total cholesterol level. Though the parameters in the intervention group reduced after an 18 month period to a certain extent, the authors did not consider them significant. However, from either group the number of patients that were admitted to the hospital for cardiac events associated with CHD, the patients in the intervention group significant reduced compared to those in the control group. The exact manner in which this effect works is still not understood clearly. However, customisation of treatment plans as per the needs of the patient has been suggested. The eighth study chosen by Ishikawa et al (2008) tested the relationship between the effect of statin and the risk factors for Japanese patients with CHD having hypercholesterolemia. In the Japanese population there are several risk factors for CHD and this was determined through the MEGA Study. Using the COX proportionate hazard model the relationship between the baseline characteristics and the CHD risk for a 5 year period was reviewed. Some of the predictors for CHD included age, gender, diabetes, hypertension, HDL levels and smoking. However, it was found that the total cholesterol level and LDL levels were not independent factors and were associated with other risk factors. The effect of pravastatin and its relationship to each risk factor was also evaluated using the COX model. Regardless of the risk factors, it was found that diet therapy along with pravastatin reduced the CHD risk by about 14 to 43% in comparison to diet therapy alone. Regardless of the presence of other risk factors, pravastatin was able to reduce the risk for CHD, and hence statins are an important factor in controlling the HDL level. The ninth study by Donner-Banzhoff and Sonnichsen (2008) studies the various approaches for effective statin administration. They discuss 2 approaches that have been utilised in the past, including the ‘fire and forget’ approach and the ‘treat to target’ approach. The fire and forget approach was a traditional approach without much of scientific evidence supporting it, whereas the ‘treat to target’ approach is more recent approach based on scientific evidences. In the fire and forget strategy, involves administrating a standard dose of statin to the patient suffering from CHD with a significant cardiovascular risk due to the high LDL levels. The dose in not titrated and there is no testing of doses involved. In the ‘treat to target’ approach, the dose of statin would be titrated against the LDL level and the response of the drug. Various other measures including the presence of other risk factors would be taken into consideration. The Guidelines in the UK propose the use of the ‘treat to target’ approach. However, various practitioners in the UK and also various studies do not follow this method and instead choose the more convenient ‘fire and forget’ approach. Hence more scientific administration of statin has been suggested in order to effectively manage hypercholesterolemia in CHD patients. The tenth study by Huijgen et al (2010) reviews the administration of another drug to be used in combination with statins in treating hypercholesterolemia in patients with CHD. The drug Colesevelam (is a bile acid sequestrant) and can be used to lower the LDL levels in the blood. It can also improve the glycaemic function in diabetics. In many patients with Familial hypercholesterolemia, it is difficult to control the LDL levels with statin and in such circumstances combination therapy with colesevelam has been suggested. 86 Patients with familial hypercholesterolemia between the ages of 18 to 75 years were included in this study and were either placed in the intervention group (which received statin, ezetimibe and colesevelam) or the control group (which received statin and ezetimibe). The drugs were administered in both groups for 12 weeks, and the primary efficacy outcome was checked after 6 weeks of administration. Secondary efficacy was checked after 12 weeks of administration. Patients in the intervention groups had lower LDL levels both after the 6 weeks and the 12 weeks check. However, gastrointestinal events in the patients who received colesevelam were slightly higher than the control group, though this figure was not significant. The drug was generally well-tolerated. The eleventh study by Howe and Jarvis (2008) demonstrated that there was a consistent flow of data that exercise helps to lower the incidence of coronary artery disease. Exercises help to improve the cardiovascular fitness, reduce obesity and maintain activity and emotional wellbeing. It has also shown to improve the HDL levels and reduce the triglyceride levels, especially when done consistently. When energy is spend in large amounts, the total cholesterol and the LDL levels are adapted for positive purposes. Immediate after the exercises are performed and in a long-term basis it helps to improve the cholesterol levels and a lot depends on the duration, intensity and type of exercises. Exercise is mostly advocated as an adjuvant therapy and certain lipids are more sensitive to exercises compared to others. Within hours of performing the exercises there would be an immediate rise in the HDL levels and a drop in the triglyceride levels. Between athletes who exercise regularly and those who lead a sedentary lifestyle, it is found that in the athletes, the HDL levels are about 40 to 50 % higher. Results Figure 5: List of Outcomes of the Literature Review From the above studies that were being assessed for the management of hypercholesterolemia in patients with CHD at the secondary prevention level, it can be proposed that pharmacological intervention plays a major role, though this therapy has to be integrated with several other techniques in order to ensure effective control of LDL and reduce the risk of critical cardiac events. Statin has proven to be a time-tested and a long-term solution for the treatment of CHD. However, there is a strong need to couple statin therapy with various other techniques that have been found to be safety and efficient and vital for the management of CHD. For a drop of 1 mmol in the LDL level , there was a reduction in cardiac mortality by about 12%, and when several other events were taken into consideration (such as major cardiac events, cardiac revascularisation, myocardial infarction, stroke, coronary death), there was a drop by about 21%. Thus it goes on to show that when LDL level control in the long term has a very good effect on cardiac morbidity and mortality, but also an even greater effect on several other events. Statins play a vital role in controlling the LDL levels, and are also considered to be safe, without a known risk for cancer (Baigent 2008). Statin is found to be more effective than a placebo in reducing hospitalisation, cardiac death, stroke, etc, in patients with CHD affected with hypercholesterolemia (Ford 2007). However, statin therapy may individually not be very effective, and positive effects have been noted when combined with other therapies. Statin along with diet therapy is much more effective than monotherapy in CHD. Statin when administered with a plant sterol (sitosterol) brought about greater LDL level than with statin alone (Fuentes 2008). Along with LDL control, it is also important to monitor the HDL levels and the triglyceride levels, as they help to control atherosclerosis. Niacin and fibrates have been proposed to control HDL and triglyceride levels (Cziraky 2008). Colesevelam, a bile sequestrant, has been suggested to be used along with statin and ezetimibe in more effective control of LDL levels in patients with CHD, and also those have co-existing diabetes (as the glycemic function would be better). Donner-Banzhoff suggests a more scientific approach of administering statins so that the effect of the drug can be ensured, and hypercholesterolemia can more effectively be managed. In the past most of the studies and clinical practice have used the ‘fire and forget’ approach which is convenient, compared to the ‘treat to target’ approach which is based on titrated the drug and reducing the dosage based on responses with the lipid levels. To ensure greater cost-effectiveness of the services that can be provided to patients with CHD having hyperlipidemia, nurse practitioners should be used to follow-up the treatment with lifestyle changes, feedback and drug therapy. When other caregivers or specialists were performing follow-up management of CHD, the treatment is not only ineffective, but also costly and not completes (Paez 2006). Besides, Murphy 2009 has suggested more comprehensive and customised treatment plans for patients and the caregivers, though the full manner in which this works is not understood clearly. However, noticeable reduction in the admission rates for cardiac events has been observed. It is also important to note that hypercholesterolemia may not be acting alone and often other risk factors such as gender, age, smoking, diabetes and hypertension would be acting to produce the risk for CHD. Hence patients with hypercholesterolemia should be monitored for other risk factors (Ishikawa 2008). Molecular testing can help differentiate from patients having a genetic link to hypercholesterolemia from an environmental risk (Alves 2010). Strong dietary management has should also be a measure along with lifestyle changes and medications. Hypercholesterolemia caused by primary hyperlipidemia has been suggested through dietary and other measures. The total calorie intake should be discussed based on age and other factors. The total body fat content should be under 20% of the body weight and should give rise to less than 30% of the calories. Carbohydrates consumed should provide about 55% of the energy requirements per day. The fat consumption should be about 10 to 15 grams per day. Along with dietary recommendations, exercises and an active lifestyle has been suggested (Schwartz, 2008). Exercises have an effect on the cholesterol level both immediately and on a long-term basis and an active lifestyle by the individual is strongly recommended. Besides, the emotional functioning would also improve (Howe, 2008) Figure 6: Statin Therapy for patients with CHD having Hypercholesterolemia Conclusion Hypercholesterolemia may be a very difficult aspect in the secondary prevention of CHD. CHD has been a very problematic issue in several of he developed nations of the world including the UK, and about 94,000 deaths every year are attributed from the condition. The paper goes into the effective management of hypercholesterolemia in patients with CHD, as the potential for cardiac events are higher. A search was conducted across 5 databases and more than 200 results were obtained, from which 10 suiting this study were selected and reviewed. The study provides certain integrated and ground-breaking results that are useful for any healthcare professional managing cases of CHD with hypercholesterolemia. The study advocates certain guidelines to be followed in the administration of Statins, as it has been found to be effective and safe when administered for long-duration. The dosage of statins should be carefully titrated based on the lipid levels of the patient, and often such treatment should be customized as per the requirements of the patients, and along with other treatment measures such as diet therapy, lifestyle changes. Besides, there is the need to administer several other drugs such as niacin, sitosterol, colesevelam, fibrates, etc, for controlling other factors along with LDL levels. 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