Abstract

Cardiovascular disease (CVD) is the leading cause of death, worldwide. In 2008, the World Health Organization (WHO) reported that 17.3 million people died from CVD, and in a global scale, this number represents 30% of deaths in the world (WHO, 2011). Currently, more than 80% of CVD related deaths occur in low or middle income nations, and by 2030, more than 23.6 million people will die from CVD related disease (WHO, 2011). In the 2010 report, coronary heart disease cost more than $108.9 billion in the US alone (CDC, 2012).

This being said there are several types and forms of cardiovascular disease, but familial hypercholesterolaemia (FH), is a rare but dangerous form of heart disease to address. FH is an autosomal dominant genetic disorder caused by mutation of the Low Density Lipoprotein Receptor (LDLR) gene located in chromosome 19.  The disease can also occur as a result of   mutations in other genes such as Apolipoprotein B (ApoB) or Proprotein convertase subtilisin/Kexin type 9 (PCSK9) or Low density lipoprotein receptor adaptor protein 1(LDLRAP1) (Robin, Tabereaux, Benza, et. al. 2007).

FH can manifest as a heterozygous or homozygous allele, and the latter is more severe and the former. The homozygous trait phenotype shows up very early in childhood in predisposed individuals. In this case study, both cases shades light to inheritance patterns, genetic screens and preventative measures, which are available for this rare but deadly disease.

 Cardiovascular System Disorder Case Study

Familial Hypercholesterolemia is a rare form of cardiovascular disorder that may occur in women, men or children, and has no age barrier. Heterozygous familial hypercholesterolemia (HeFH) Familial Hypercholesterolemia is a rare form of cardiovascular disorder, which can occur among women, men or children, and has no age barrier. Heterozygous familial hypercholesterolemia (HeFH) penetrance is 1 in every 500 individuals and the homozygous familial hypercholesterolemia (HoFH) occurs in 1 out of 1 million people (Zhang, Yang, et.al. 2010). The HoFH is more severe than HeFH, and phenotypically develops at early childhood causing calcification of the Aortic artery (Aortic stenosis), and if not treated, the disease can lead to death (Zhang, Yang, et.al. 2010). In the case where the Aortic stenosis is severe, an aortic valve replacement is usually recommended.

A disorder such as this, which causes high accumulation of low density lipoprotein (LDL) in the blood vessels, could be caused by mutation in LDLR or ApoB, thereby providing low or no binding affinity to LDL, and thus, making it almost impossible, metabolically to remove LDL from the blood vessel (Robin, et.al. 2007). The HeFH and HoFH have similar symptoms, but treatment and diagnostic methodologies are slightly different because of the allelic zygosity trait of the disease.

Regardless of whether FH condition is the HeFH or HeFH trait, both have common forms of fatty acids deposits on the skin (Xanthomas), cholesterol deposits on the eyelids (Corneal arcus), high level of LDL in lipid test, lumps in the tendons of hands, knees, elbows and Achilles (Tendon Xanthomas) (ADAM, 2010). The cumulative LDL deposit in the walls of the blood vessels eventually leads to chest pain (angina pectoris), ischemic attacks and stroke.

HeFH, the mono-allelic trait, is usually treated with statins or nicotinic acids. On the other hand, HoFH is harder to treat due to the severity of its biallelic trait.  Thus, high dose of statin and LDL apheresis are recommended, and when this disease is not controlled properly, it will lead to complications such as heart attack and other heart diseases (ADAM, 2011). In some severe cases where the disease cannot be controlled with medication; liver transplant, shunt implants or other surgical bypass are necessary.

FH can be extremely destructive and may increase the risk of other heart disease, health complications, kidney failure, liver damage, stroke and atherosclerosis. In addition, FH has an increased risk and severity among smokers, alcoholics, high blood pressure patients, obese and individuals that are physically inactive (CDC, 2012).

Regular exercise is strongly recommended for predisposed individuals. In addition, lifestyle change such as abstaining from eating a saturated-rich diet, meats and eliminating coconut and palm oil products, is highly recommended in order to regain a healthy cholesterol level (ADAM, 2011).

Probands and people that have a family history of the disease are mainly at high risk because the chances of having a biallelic copy of the autosomal dominant copy of the gene is 50% probability when one parent has a biallelic gene, and the other is a carrier (mono-allelic). Therefore, early genetic test and preventative measure to avoid a severe condition and complication are very important.

With advanced technology such as the noninvasive transthoracic doppler echocardiography (TTDE), C-reactive protein (CRP) and Lipoprotein-associated phospholipase A2 (LAPA2) early detection procedure for the disease is possible.

C-reactive protein marker is a five 23kDa subunit pentraxin marker of inflammation and innate immune response. CRP is a bio-marker for many diseases including heart disease.  Thus, regular CRP base-line checkup can prospectively detect FH associated stroke, unstable angina and atherothrombosis.

Furthermore, based on several scientific studies, lipoprotein-associated phospholipase A2 (LAPA2) is an enzyme that hydrolyzes phospholipids at the Sn2 position to produce lysophospholipids and fatty acid by-products. This enzyme is associated with atherogenesis and high risk of coronary heart disease; hence, it is an important bio-marker for the disease (Packard, O’Reilly, Caslake, et.al. 2010). Thus, the ability to test for these multifactorial variables associated with FH episode or the tendency of prospectively predicting FH severity will lead to future product developments for this disease.

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