Treatment for the Genetic Mutation in FH - Term Paper Example

?INTRODUCTION Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lifelong elevation low density lipoprotein-cholesterol (LDL-C) in the plasma (Al-Allaf, et al., 2010). As well, it is the best-characterized genetically-transmitted risk for hyperlipidemia (Jacobson, 2007). Many are afflicted with this disease. In fact, it is the most frequent Mendelian disorder (Al-Allaf, et al., 2010). 90% of cases is caused by a mutation at chromosome 19, specifically in the gene coding for hepatic cell surface low density lipoprotein (LDL) receptors, which is responsible for sequestering cholesterol from the bloodstream through endocytosis and intracellular degradation during lipoprotein metabolism (Al-Allaf, et al., 2010; Jacobson, 2007). The remaining cases of FH is caused by a mutation in the gene encoding for apolipoprotein B-100 (ApoB-100), located at the short arm of chromosome 2, which reduces ligand affinity for the normal receptors. As a result, plasma concentration of LDL-C increases (Al-Allaf, et al., 2010). The more common heterozygous FH is diagnosed by an average LDL-C level of greater than 160 mg/dl for two measurements (Jacobson, 2007). It is said that 1: 500 individuals suffer from it, more than those who have homozygous cystic fibrosis and sickle cell anemia. Typically, serum cholesterol is at 250-450 mg/dl (6.5-11.6 mmol/L) and LDL-C is at 200-400 mg/dl (5.2-10.4 mmol/L) (Al-Allaf, et al., 2010). Early intervention only warrants lifestyle changes, while therapeutics are needed in late cases where lifestyle modifications are already ineffective (Jacobson, 2007). On the other hand, the rare homozygous FH is characterized by total serum cholesterol levels of greater than 500 mg/dl (13 mmol/L) and LDL-C levels of greater than 450 mg/dl (11.7 mmol/L). It occurs in 1: 1, 000, 000 individuals. As a result of hypercholesterolemia, xanthoma on the tendons of the distal extremities and premature development of corneal arcus exist among individuals with homozygous FH. In addition, they develop cardiovascular diseases earlier relative to those with heterozygous FH (Al-Allaf, et al., 2010). FH carriers, on the other hand, are much more difficult to detect as they present with a wide variety of signs and symptoms (Broekhuizen et al., 2010). . There is no current treatment for the genetic mutation in FH, since studies on the effectiveness of gene therapy with surgical intervention are still ongoing (Al-Allaf, et al., 2010). However, if the signs and symptoms of FH are ignored, it can lead to premature fatal cardiovascular diseases, stroke and myocardial infarction (Daskalopoulou, Doonan and Mikhailidis, 2010). It increases the risk for hastened arterial plaque development, which normally begin in early childhood and peak during adolescence (Jacobson, 2007). It is thus important to prevent these cardiovascular changes from happening so that better physical and social outcomes can be achieved and healthcare costs are minimized (Al-Allaf, et al., 2010; Broekhuizen et al., 2010). SUMMARY OF FINDINGS Approach on patient with hypercholesterolemia A person with high lipid levels is worked-up based on the stage of the disease at which presents. Hyperlipidemia in an otherwise healthy patient without family history of early myocardial infarct, stroke or peripheral vascular disease, only warrants basic lifestyle patient education regarding proper diet, exercise, and smoking prevention. Diet diary, food frequency questionnaire, and inquiries on usual food intake during the interview can illicit points at which dietary restrictions can be focused on. Meanwhile, if family history is present, fasting lipid profile is needed to determine whether average LDL-C is greater than 160 mg/dl, in which case the target LDL-C is set at below 130 mg/dl and therapeutic lifestyle changes (TLC) are advised (Jacobson, 2007). Non-pharmacological management In managing patients with FH, it is important to prioritize risk factors and to intervene them in a step-wise manner. In dietary modifications, decreasing intake of sources of saturated fat and simple sugars should be focused on. As well, patients, especially the physically-capable ones, should also be given a choice in terms of the changes in physical activities he or she should do to manage his or her disease. It is important to agree with the patient in terms of the lifestyle modifications he or she is willing to undergo so that adherence becomes easier. TLC is a step-wise list of lifestyle modifications that FH can undergo to prevent progression of disease. Gradual changes include weight lifting with lighter weights, increased physical activity, smoking prevention or cessation, targeted dietary restriction (Jacobson, 2007). Non-pharmacologic management is important as not only lowers LDL-C levels, but it also reduces the risk for cardiovascular diseases (Broekhuizen et al., 2010). Medical management In cases wherein TLC for one to two years proved to be ineffective in maintaining LDL-C levels, HMG-CoA reductase inhibitors, commonly known as statins, should be prescribed. Statins are the mainstay drugs for this condition, because it is the most effective lipid-lowering drug with the best tolerance across all ethnic groups, sexes and ages (Al-Allaf, et al., 2010). Discontinuation or intermittent use, through biological rebound phenomenon, may lead to higher probability of cardiovascular and cerebrovascular diseases, revascularization, and coronary artery disease. However, they produce rare dose-dependent adverse effects (Daskalopoulou, Doonan and Mikhailidis, 2010) on muscle, liver and pregnancy (Jacobson, 2007). In fact, increasing the statin dose to 80 mg is associated with liver toxicity or myopathy (Al-Allaf, et al., 2010). While under medications, the patient should also be advised to monitor lipids, creatinine phosphokinase, ALT and AST levels that can help in assessing the effects on the body (Jacobson, 2007). Presence of adverse reactions should prompt changing of medications to other cholesterol-lowering agents such as bile acid resin, niacin, fibrate, or cholesterol absorption inhibitor (Al-Allaf, et al., 2010). Despite maintenance of LDL-C levels through statins, FH patients remain to be at risk of developing cardiovascular problems. In preventing such occurrences, it is important to 1) improve adherence to statin therapy and 2) lifestyle modifications (Broekhuizen et al., 2010). Positive factors in attainment of LDL-C target Normal morphometric measures, absence of smoking and metabolic syndrome, good adherence to statins, and awareness of current LDL-C levels are positive factors for the attainment of LDL-C goals. As well, it was found that women, residents of nursing homes, and people with comorbidities have better treatment adherence (Daskalopoulou, Doonan and Mikhailidis, 2010). Factors contributing to difficulty in controlling LDL-C Patients with hypercholesterolemia are having a difficult time in keeping levels of LDL-C within a strict range (1.8-2.6 mmol/L or 70-100 g/dl for patients with high cardiovascular risk, and less than 3.31 mmol/L or 129 mg/dl for those with moderate cardiovascular risk) (Daskalopoulou, Doonan and Mikhailidis, 2010; Broekhuizen et al., 2010; Al-Allaf, et al., 2010). Apparently, primary prevention, secondary prevention, and the metabolic syndrome patients are all similarly at risk to increased LDL-C levels. In eight European countries, only about half hit the target LDL-C levels. Lack of patient adherence, together with under-prescription of statins, contributes to this difficulty of keeping LDL-C levels checked (Daskalopoulou, Doonan and Mikhailidis, 2010). Generally, adherence to lifestyle modifications and medical management ranges from 20% to 90%, with most people graded at 50%. Various factors affect a patient’s adherence to treatment. Health beliefs such as risk perception, perceived effects of treatment and self-efficacy, as well as stage of change and communication problems with physicians partly contribute to lack of adherence. In addition, patients usually have difficulty in grasping their risk for developing cardiovascular diseases, leading to difficulty in acting upon these pieces of information. It is thus not surprising to illicit frictions and irritations among health advisors and patients during consultations, may it be community- or individual-oriented management of disease (Koelewijn-van Loon, et al., 2008). Reasons for difficulty in lifestyle modifications Adherence to lifestyle modifications is usually not optimal, despite being effective and relatively cheap, since changing lifestyle is usually very difficult (Koelewijn-van Loon, et al., 2008). Reasons for difficulty in adherence to medical management It was found that 12% of FH patients did not take prescribed medications at all, and 6.4% of hypercholesterolemia patients discontinued statin therapy after discovery of their genetic condition (Broekhuizen et al., 2010). Decision to regularly continue therapy is thus dependent on other factors, such as presence of side effects, perception of drug ineffectiveness and possibly, hopelessness of getting rid of such condition. In the case of statins, side effects are present, albeit rare. Wrong notion of drug ineffectiveness can be nurtured by the absence of frequent and regular monitoring of a dependent variable, in this case LDL-C levels. Moreover, complacency regarding the morbidity of one’s condition can prove to be significant in causing difficulty in treatment adherence (Daskalopoulou, Doonan and Mikhailidis, 2010; Broekhuizen et al., 2010). Patients with difficulty in maintain target LDL-C levels have been noted to be doing poorly in reaching other cardiovascular risk goals such as limiting HbA1c, triglyceride and blood pressure, as well as increasing high density lipoprotein-cholesterol (HDL-C) levels. Improving management adherence Adherence to medical management requires both educational and behavioral components. Initially, any wrong perception about his or her condition and the benefits and disadvantages of treatment should be corrected. According to Koelewijn-van Loon, et al., (2008), increasing the patient’s competence in understanding the nature of his or her disease and involving them in decisions regarding management lead to better-informed decisions. Ways of improving adherence Improving adherence needs an open interaction between patients and doctors. What was found to be most beneficial to management adherence is when the patient acts as the decision-maker, while physicians will play the role of teachers or friends that will present the different options of management (Koelewijn-van Loon, et al.,2008). In lifestyle modifications, patients must be taught how to assess their own body, especially their body mass indices (BMI) and LDL-C levels, and how to manage them first by a well-planned diet and exercise. It may benefit from motivational interviewing, which uses the basic principles of expressing empathy, developing discrepancy, rolling with resistance and supporting self-efficacy to instigate motivations for behavior change to healthier ones. In addition, motivational interviewing can be used to allow physicians or nurses to set goals and specific action plan of therapy with patients and to determine patient’s motivation to be healthy (Koelewijn-van Loon, et al., 2008). For those under statin therapy, it is important to inform the patient about the repercussions of intermittent use of the drug. This may need decision aids, which are well-designed and validated integration of treatment options used to help healthcare practitioners and patients in making the best decision (Koelewijn-van Loon, et al., 2008). Individualized management is also important in giving patients treatment approaches which are manageable and effective in their opinion. Teaching patients on how to monitor their own condition not only eradicates the wrong notion of drug ineffectiveness, but also empowers the patients as well. The importance of monitoring these factors can also be taught to patients as well. In addition, they should be advised to prevent increased alcohol intake and chronic obstructive pulmonary disease (COPD) as they can significantly increase the risk of developing morbidities (Daskalopoulou, Doonan and Mikhailidis, 2010). CONCLUSION It is important to have a comprehensive patient education, involving both statin and non-pharmacological therapy, in dealing with their FH. Raising awareness of their current condition and risk of the development of others, lifestyle improvement and statin compliance must all be taught to these patients. Specifically, they must know how to assess and improve their own body through diet and exercise. In addition, they should also be aware of the presence of other risk factors for developing cardiovascular co-morbidities. Aside from educating the patients with the lifestyle modifications they need to undergo, the basics on pharmacodynamics of statins, most importantly its manifested effects, should also be taught to patients. Monitoring these should be advised in order to intervene against adverse drug reaction. However, no formula can be used in educating patients with FH. An individualized management and patient education, in which the patient makes the decisions based on the options laid out by doctors or nurses, should be provided so that adherence becomes easier. References Al-Allaf, F. A., Coutelle, C., Waddington, S. N., David, A. L., Harbottle, R., and Themis, M. (2010). LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives, International Archives of Medicine, 3(36) Broekhuizen, K., van Poppel, M. N. M., Koppes, L. K. J., Brug. J., and van Mechelen, W. (2010). A tailored lifestyle intervention to reduce the cardiovascular disease risk of individuals with Familial Hypercholesterolemia (FH): design of the PRO-FIT randomised controlled trial. BMC Public Health, 10(69) Daskalopoulou, S. S., Doonan, R. J. and Mikhailidis, D. P. (2010). Undertreatment of Hypercholesterolemia. CMRO, 26(2), 439-443. Jacobson, M. S. (2007). Atherosclerosis Prevention and Cholesterol Management in Adolescents. Adolescent Health Update, 19(3). Koelewijn-van Loon, M. S., van Steenkiste, B., Ronda, G., Wensing, W., Stoffers, S. E., Elwyn, G., Grol, R., and van der Weijden, T. (2008) Improving patient adherence to lifestyle advice (IMPALA): a cluster-randomised controlled trial on the implementation of a nurse-led intervention for cardiovascular risk management in primary care (protocol). BMC Health Services Research, 8(9) Read More