Dyslipidemia

As discussed above, insulin suppresses the breakdown of triglyceride within fat cells in the post-prandial period, preventing release of fatty acids from adipocytes in healthy individuals. Insulin also stimulates triglyceride clearance from triglyceride-rich lipoprotein particles and the esterification of fatty acids to form the intra-adipocyte triglyceride store. 

---

As yet, no human diseases have been identified as a result of FATPl mutations. However, genetic polymorphisms in the human FATPl gene have been linked to dyslipidemia. An A/G exchange at position +48 in intron 8 of the FATPl gene has been shown to result in increased TG concentrations in female but not in male subjects. In a second study, the same polymorphism was linked to increased postprandial TG concentrations and smaller low density lipoprotein (LDL) particles. To date, it is still unknown if this polymorphism is associated with altered levels of FATPl expression and/or function. 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

PPARa Liver, heart, skeletal muscle, atherosclerotic lesions TG- and LDL-C-lowering and HDL-C-raising re-directs excess cholesterol from the peripheral tissues to the liver for excretion into the bile via HDL-C slowed progression of atherosclerosis Fatty acids, eico-sanoids (fatty acids derived from FAS ) Fibrates fenofibrate (Tricor ), genfibrozil (Lopid ) Dyslipidemia... 

PPAR5 Ubiquitous Potent TG- and LDL-C-lowering and potent HDL-C-raising increased oxidative disposal of fatty acids in adipose and skeletal muscle thermogenesis weight loss Fatty acids, eicosanoids (fatty acids derived from VLDL particles ) GW501516 currently in Phase II clinical trials Dyslipidemia, obesity atherosclerosis ... 

Although no PPARS-specific ligands are currently FDA-approved, GW501516 is a compound being developed jointly by GlaxoSmithKline and Ligand Pharmaceuticals. This compound is currently in Phase II trials for the treatment of dyslipidemia. 

The dramatic decrease in the morbidity and mortality of HIV-infected individnals in the last decade, due to the wide use of HAART, has been somewhat tempered by the emergence of mid-long term toxicities. A characteristic body fat redistribntion and metabolic changes, inclnding dyslipidemia and insnlin resistance, are amongst the most prevalent and worrisome consequences (Carr et al. 2003). As HIV-infected individnals have increasing life expectancies, the risk for cardiovascnlar complications has emerged as an important canse of morbidity and mortality and preventive measnres should be considered to minimize their impact (Weber et al. 2006). 

FIGURE 4.5 A 72-year-old man with medical history remarkable for hypertension and dyslipidemia presented with posterior circulation infarct (a). CTA and posterior circulation angiography (left vertebral artery injection) performed demonstrated severe mid-basilar artery stenosis (b and c). Left vertebral artery injection demonstrated near-complete reversal of the stenosis after a drug-eluting balloon expandable stent (Cypher, Cordis Johnson Johnson) was deployed (d). 

Dyslipidemia Microalbuminuria Family history Central obesity Physical inactivity Tobacco use... 

Lifestyle changes should address other risk factors for cardiovascular disease including obesity, physical inactivity, insulin resistance, dyslipidemia, smoking cessation, and others. 

Factors that predispose an individual to IHD are listed in Table 4—2. Hypertension, diabetes, dyslipidemia, and cigarette smoking are associated with endothelial dysfunction and potentiate atherosclerosis of the coronary arteries. The risk for IHD increases two-fold for every 20 mm Hg increment in systolic blood pressure and up to eight-fold in the presence of diabetes.5,6 Physical inactivity and obesity independently increase the risk for IHD, in addition to predisposing individuals to other cardiovascular risk factors (e.g., hypertension, dyslipidemia, and diabetes). 

Patients with multiple risk factors, particularly those with diabetes, are at the greatest risk for IHD. Metabolic syndrome is a constellation of cardiovascular risk factors related to hypertension, abdominal obesity, dyslipidemia, and insulin... 

A major component of any IHD treatment plan is control of modifiable risk factors, including dyslipidemia, hypertension, and diabetes. Treatment strategies for dyslipidemia and hypertension in the patient with IHD are summarized in the following paragraphs. Visit chapters in this textbook on the management of hypertension and dyslipidemia for further information. 

Because lipoprotein metabolism and the pathophysiology of atherosclerosis are closely linked, treatment of dyslipidemias is critical for both primary and secondary prevention of IHD-related cardiac events. In 2001, the Adult Treatment Panel III of the National Cholesterol Education Program... 

Like dyslipidemia, hypertension is a major, modifiable risk factor for the development of IHD and related complications. Unfortunately, awareness, treatment, and control of blood pressure are not nearly enough.30 Aggressive identification and control of hypertension is warranted in patients with IHD to minimize the risk of major adverse cardiac events. Goal blood pressure in patients with IHD is less than 140/90 mm Hg or less than 130/80 mm Hg in patients with diabetes. Because of their cardioprotective benefits, 3-blockers and ACE inhibitors (or ARBs in ACE-inhibitor-intolerant patients), either alone or in combination, are appropriate for most patients with both hypertension and IHD. 

Hypertension x 12 years dyslipidemia x 10 years obesity x 20 years degenerative joint disease x 5 years recurrent urinary tract infections... 

Recommend appropriate therapeutic lifestyle changes (TLC) and pharmacotherapy interventions for patients with dyslipidemia. 

Describe the components of a monitoring plan to assess effectiveness and adverse effects of pharmacotherapy for dyslipidemias. 

After assessment and control of LDL cholesterol, patients with serum triglycerides of 200 to 499 mg/dL (2.26 to 5.64 mmol/L) should be assessed for atherogenic dyslipidemia (low HDL cholesterol and increased small-dense LDL particles) and metabolic syndrome. 

Patients with metabolic syndrome are twice as likely to develop type 2 diabetes and four times more likely to develop CHD.3,11 These individuals are usually insulin resistant, obese, have hypertension, are in a prothrombotic state, and have atherogenic dyslipidemia characterized by low HDL cholesterol and elevated triglycerides, and an increased proportion of their LDL particles are small and dense.3... 

Compared with monotherapy, combination therapy is relatively unstudied in terms of the effects on CHD event reduction and may reduce patient compliance through increased side effects and increased costs. When used appropriately and with proper precautions, however, they are effective in normalizing lipid abnormalities, particularly in patients who cannot tolerate adequate doses of statin therapy for more severe forms of dyslipidemia. 

Both parents alive father has history of hypertension, type 2 DM, and dyslipidemia mother has a history of colon cancer with subtotal colectomy brother with history of "indeterminate colitis"... 

Non-alcoholic fatty liver disease begins with asymptomatic fatty liver but may progress to cirrhosis. This is a disease of exclusion elimination of any possible viral, genetic, or environmental causes must be made prior to making this diagnosis. Non-alcoholic fatty liver disease is related to numerous metabolic abnormalities. Risk factors include diabetes mellitus, dyslipidemia, obesity, and other conditions associated with increased hepatic fat.26... 

---