Dyslipidemia is defined as elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides; low high-density lipoprotein (HDL) cholesterol; or a combination of these abnormalities.
WHAT ARE THE CAUSES OF DYSLIPIDEMIA?
Cholesterol, triglycerides, and phospholipids are transported in the blood as complexes of lipids and proteins (lipoproteins). Elevated total and LDL cholesterol and reduced HDL cholesterol are associated with the development of coronary heart disease (CHD).
Risk factors such as oxidised LDL, mechanical injury to endothelium, and excessive homocysteine can lead to endothelial dysfunction and cellular interactions culminating in atherosclerosis. Eventual clinical outcomes may include angina, myocardial infarction (MI), arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, and sudden death.
Atherosclerotic lesions arise from transport and retention of plasma LDL through the endothelial cell layer into the extracellular matrix of the subendothelial space. Once in the artery wall, LDL is chemically modified through oxidation and nonenzymatic glycation. Mildly oxidised LDL recruits’ monocytes into the artery wall, which transform into macrophages that accelerate LDL oxidation. Oxidised LDL provokes an inflammatory response mediated by chemoattractants and cytokines.
Repeated injury and repair within an atherosclerotic plaque eventually lead to a fibrous cap protecting the underlying core of lipids, collagen, calcium, and inflammatory cells. Maintenance of the fibrous plaque is critical to prevent plaque rupture and coronary thrombosis.
Primary or genetic lipoprotein disorders are classified into six categories: I (chylomicrons), IIa (LDL), IIb (LDL + very-low-density lipoprotein [VLDL]), III (intermediate-density lipoprotein), IV (VLDL), and V (VLDL + chylomicrons). Secondary forms of dyslipidemia also exist, and several drug classes may elevate cholesterol levels (e.g., progestins, thiazide diuretics, glucocorticoids, β-blockers, isotretinoin, protease inhibitors, cyclosporine, mirtazapine, and sirolimus). The primary defect in familial hypercholesterolemia is the inability to bind LDL to the LDL receptor (LDL-R). This leads to a lack of LDL degradation by cells and unregulated biosynthesis of cholesterol.
WHAT ARE THE SIGNS AND SYMPTOMS OF DYSLIPIDEMIA?
Most patients are asymptomatic for many years. Symptomatic patients may complain of chest pain, palpitations, sweating, anxiety, shortness of breath, or abdominal pain. They may also experience difficulty with speech or movement or loss of consciousness.
Depending on the lipoprotein abnormality, signs on physical examination may include cutaneous xanthomas, peripheral polyneuropathy, high blood pressure, and increased body mass index or waist size.
Genomic Medicine UK is the home of comprehensive genomic testing in London. Our consultant medical doctors work tirelessly to provide the highest standards of medical laboratory testing for personalised medical treatments, genomic risk assessments for common diseases and genomic risk assessment for cancers at an affordable cost for everybody. We use state-of-the-art modern technologies of next-generation sequencing and DNA chip microarray to provide all of our patients and partner doctors with a reliable, evidence-based, thorough and valuable medical service.