Chronic Inherited Condition - Familial Hypercholesterolemia (Term Paper Sample)

Familial Hypercholesterolemia
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Familial Hypercholesterolemia
Familial hypercholesterolemia (FH) is potentially a common monogenic conditions likely to be encountered by the general practitioner. According to the global statistics from the World Health Organization, the prevalence of FH is assessed as approximately 1:500. However, this scale is in the individuals with the founder effect where the condition is estimated to be as higher as 1:70. The disease remains hugely underdiagnosed as well as under-treated. In the United States, it has been determined that over 80% of people with FH are not diagnosed. According to Nordestgaard et al., (2013), early identification as well as management of FH might save the lives of numerous individuals up to 40% particularly those who don’t survive an initial myocardial infarction. In this light, this scope sets out to describe an epidemiologic approach of planning a screening program for FH. As a chronic condition, the Familial Hypercholesterolemia is constituted by the abnormal high levels of low-density lipoprotein cholesterol in the blood.
In this regard, this discourse follows on four progressive sections that expound more on the epidemiologic consideration of planning a screening program for the condition. The first part will explore the epidemiologic parameters as well as significance of FH. Also, Specific genetic markers of FH will be explored in the second section while the third section will evaluate the environmental and lifestyle factors that have been linked to the expression of FH. Consequently, in the final section a screening plan will be developed for the individuals at high risk for developing FH.
Significance of Familial hypercholesterolemia
According to the World Health Organization (WHO), over 250 million people are at a vulnerable state of premature death following the fact that they carry one gene that heighten the genetic lipid disorders. FH is a chronic disorder with an autosomal prevailing inheritance mode that is influenced by the mutation of the genes that further encodes the LDL receptor. In essence, LDL receptor is a protein that maintains cholesterol homeostasis. For this reason, FH results lead to severe elevation of blood cholesterol levels. According to Raal et al., (2015) FH Familial Hypercholesterolemia is revealed to affect up to 1.5 million of people in the United States, Where it is projected that 1 in 250 people will be born with FH. As established earlier, early detection and management of FH mitigates the risk and profoundly reduces it to 80%. Nonetheless, most of the individuals with FH have never been diagnosed or treated (Benn et al., 2016). This chronic condition also marks as a critical precursor to several chronic diseases including heart attacks, strokes, as well as atherosclerosis. More importantly, the primary concern of Familial Hypercholesterolemia revolves around how often it goes underdiagnosed and undertreated, which further leads to an early onset of health complexities such as ischemic events, cardiovascular disease and other health problems known to potentially cause premature death (Ferranti et al., 2016). For this reason, FH marks as an essential health topic that needs probable measures of campaigning for the screening practices as the condition can be managed at an early stage to prevent irreversible damage to the heart.
More on this, FH is a condition of grave concern following the fact that the highest estimate of patients identified ranks at 50%, but only a fraction of these is receiving statin therapy as well as less are well controlled. On a positive side, it would be accurate to derive that the best case scenario for screening is that a maximum of 25% of all FH patients is adequately treated. Although western nations have the highest degree of identification as well as optimal control of the patient, there's still need for relevant measures to attain optimal control of this life-threatening disorder as the percentage of well-controlled patients has never surpassed 50%.
Genetic markers linked to Familial Hypercholesterolemia
FH is triggered by three genes in lipoprotein trails as well as exhibits distinctive gene-dose properties. The genetic factor consist of autosomal receding hypercholesterolemia (ARH) adaptor protein, Apolipoprotein (apo) B, proprotein convertase subtilisin/Kexin 9, as well as the low-density lipoprotein (LPD) receptor. In essence, the disorders are all defective clearance of LDL across an intricate component of lipid as well as lipoprotein regulation and metabolism (Cuchel et al., 2013). Normal Lipoprotein metabolism and cellular cholesterol are assessed prior to describing the disorder. FH is further categorized into two phenotypes of conditions based on the relentlessness of the metabolic disorder. However, the most vigorously genetic heterozygous phenotype consists of deficiencies in apo B100, LDL receptor as well as neural apoptosis monitoring cleavage protein. To better grasp these gene markers, it would be imperative to analyze them in depth. Primarily, the LDL Receptor Gene generates a protein that facilitates the removal of cholesterol from the blood. However, for patients with FH, the gene is often altered. On the other hand, the (apo) B Gene, is responsible for generating a protein that maintains lipoproteins together in the blood. However, when this gene is altered it becomes challenging for the liver cells to bind to the protein as well as get rid of LDL cholesterol from the blood (Martin et al., 2017). Consequently, the PCSK9 Gene goes an extra mile towards creating an enzyme that controls the breakdown of proteins in the LDL receptors of the liver. Nonetheless, when the gene is altered, there are fewer receptors on the liver cells to pick up and get rid of excess cholesterol. According to Langsted et al., (2016), FH is a dominant genetic condition that puts offspring of the patient with this trait a risk of inheriting the condition by 50%. In a study conducted by Benn et al., (2016) also shows that the genes are affected during the sequencing of the DNA on chromosome 19.
Environmental and Lifestyle factors influencing FH
According to numerous multigenerational family studies, FH is linked to various lifestyles factors, and mortality varies over time is due to the increase in dietary fat and sedentary lifestyles. Cuchel et al., (2013) illustrates the gene interaction with environmental factors through comparing phenotypic expression of Heterozygous FH geographically. It is, therefore, established that Obesity is among the lifestyle factors that go an extra mile towards expediting the onset of FH. Langsted et al., (2016) also add that genetic factors related to obesity phenotypes such a hypothyroidism profoundly instigates FH, particularly among those with inherited traits. According to Wiegman et al., (2015) obese individuals and those living sedentary lifestyles have a probable chance of developing FH in an estimated scale of 1:172 compared to non-obese individuals and those with a custom of living healthy lifestyles.
In a study by Kastelein et al., (2015), predisposed genes are identified as uncontrollable factors, but the authors contend that the modification of lifestyle can go a long way towards reducing the onset of FH. For this reason, the researchers propose various measures of molding one's lifestyle including smoking cessation, regular exercise such as jogging, yoga and palates, healthy diet modification and leading an active lifestyle (Nordestgaard et al., 2013). Therefore, with the change of one's lifestyle to suit these factors, the severity of FH would be mitigated.
Screening recommendation for FH
Sensitivity and Nature of current methods
Prior to exploring the screening plan for FH, it would be imperative to derive that FH has no official disease cluster under the World Health Organization for disease clarifications. Primarily, screening has traditionally been performed through a selection where Sanger sequencing is profoundly found to have value but otherwise shown to be excessively costly. However, Farnier et al., (2017) reveal that the Next Generation Sequencing (NGS) shows excellent promise following its ability to perform parallel sequencing rapidly. Nonetheless, Cascade Screening is identified as the best screening method where family members are traced from a recognized FH index-case and is cost-effective compared to current strategies. According to Langsted et al., (2016), a significant portion of the first degree relative of the recognized index-case is often discovered to contain FH mutation. For this reason, it has also been recommended in NICE guidelines that genetic testing where the causative mutation the index case has been identified ought to be used to avoid under-diagnosis.
Recommendations
Following the fact that most of the individuals with FH developed it through predisposing genetic factors, it would be imperative to focus secondary prevention strategies to mitigate the prevalence of this condition better. The secondary screening plan would be utilized throughout health care facilities to educate patients about FH risk factors and encourage regular screening for those with risk factors (Nordestgaard et al., 2013). Moreover, it would provide health education for patients with FH which would go an extra mile towards increasing the success of treatment plan. More importantly, it would lead to an early detection of FH which will be beneficial throughout their lifetime through preventing other health problems such as an early onset of Coronary Heart Disease through assessing Common external signs of FH include lipid deposits around the eyelids, knuckles, and knees (Kastelein et al., 2015).
According to reports from the Center for Disease Control and Prevention (CDC) and WHO, children and adolescents have the lowest ...