The Problem Of High cholesterol Levels And Coronary Heart Disease

The human being is a biological factory that produces myriad products for its survival. From hormones to energy based metabolic pathways, all need lipids. Cholesterol is the omnipotent mother lipid from which derive subsidiary lipids or ‘Lipoproteins’ as they are called viz LDL , VLDL and HDL, abbreviated terms for Low Density, Very Low Density and High Density Lipoproteins.
With such a ubiquitous role in the human body, abnormal lipid levels are likely. High Cholesterol levels translate into spare fat deposits in blood vessels leading to atherosclerosis and Coronary Heart Disease (CHD).

Epidemiology

Among adults, National Health and Nutrition Examination Survey III data (1988-1992) show more frank hypercholesterolemia among non-Hispanic white persons (19%) than Mexican Americans (15%) or non-Hispanic black persons (16%). Hypercholesterolemia is more common in men younger than 55 years and in women older than 55 years. In adults, hypercholesterolemia increases with advancing age.

Why Treat Hypercholesterolemia

Polygenic hypercholesterolemia is associated with an increased risk for coronary heart disease (CHD). The primary manifestation of hypercholesterolemia is increased CHD risk.
The results of clinical trials that have conclusively demonstrated reduced morbidity and mortality in subjects with moderate hypercholesterolemia treated with cholesterol-lowering agents, particularly (though not exclusively) statins.

Etiology

This condition is caused by a susceptible genotype aggravated by an atherogenic diet (excessive intake of saturated fat, trans fat, and, to a lesser extent, cholesterol), obesity, and sedentary lifestyle. Diets high in saturated fat, trans fat, and cholesterol cause a reduction in LDL receptors in the liver, thus retarding LDL catabolism. The Western lifestyle of a high-fat diet superimposed on a susceptible genotype appears to cause hypercholesterolemia.
Nonetheless, ensuring that the patient does not have untreated hypothyroidism, renal disease, or liver disease is important.
Furthermore, progestins, anabolic steroids, and glucocorticoids may adversely affect low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values.

Risk Factors For Coronary Heart Disease

The risk factors for coronary heart disease (CHD), other than LDL-C and age or sex distribution include:
Family history of premature coronary heart disease (male first-degree relative <55 years, female first-degree relative <65 years),
Current cigarette smoking and
Hypertension – Blood pressure greater than or equal to 140/90 mm Hg or current antihypertensive drug therapy.

Pathophysiology

Low-density lipoprotein (LDL) particles are the major plasma carriers of cholesterol. Therefore, in patients with normal or minimally elevated triglyceride levels and average high-density cholesterol levels (HDL-C), the total serum cholesterol measurement can be used as a surrogate for the LDL-C level.
Hypertriglyceridemia is caused by excessive numbers of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and/or chylomicron particles; and in this situation the total cholesterol level is not a reflection of the LDL-C level.

Normal Values Of Blood Cholesterol

The guidelines of the American Heart Association and the NCEP Adult Treatment Panel III (ATP III) define hypercholesterolemia as a blood cholesterol concentration of greater than or equal to 240 mg/dL. Desirable or normal Values Of Blood cholesterol concentrations are less than 200 mg/dL.

Investigating Hypercholesterolemia

The US National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) suggests screening asymptomatic individuals with a fasting lipid panel every 5 years. A full lipid profile is obtained after the patient fasts for 9-12 hours. Chylomicrons must be absent and the total triglyceride level must be less than 400 mg/dL in order to use the Friedewald formula to calculate LDL-C.
The Friedewald formula is LDL-C = total cholesterol – high-density lipoprotein cholesterol (HDL-C) + triglycerides/5. Direct LDL-C measurements do not offer any greater use, except in patients with marked hypertriglyceridemia. Direct LDL-C measurements can be performed while the patient is in the nonfasting state. It is prudent to ascertain all medication intake and perform tests of serum thyroid-stimulating hormone, liver function, creatinine, and urinalysis to rule out secondary dyslipidemias.

Treating High Cholesterol Levels

Medical therapy involves lifestyle modification and pharmacologic therapy.

Natural Remedy For Cholesterol – Lifestyle Modification

We can reduce Cholesterol naturally by the means listed below. They include exercise as well as dietary modifications.
The reduction of saturated fat intake is vitally related to reduced low-density lipoprotein cholesterol (LDL-C) levels. In general, replacing fat with complex carbohydrates is helpful. Because carbohydrates are less calorically dense than fat, this substitution may also help prevent obesity.
Dietary guidelines are as follows: Total fat – Less than 30% of energy intake (calories), Saturated fat – Less than 7%, Polyunsaturated fat – Less than 10%, Monounsaturated fat 10-15% and Carbohydrates 50-60% of energy intake.
Aerobic exercise may improve insulin sensitivity, high-density lipoprotein cholesterol (HDL-C) concentrations, and triglyceride levels and, thus, may help reduce CHD risk.

Reducing Coronary Heart Disease Risk By Drugs

STATINS
The statin (HMG-CoA reductase inhibitor) class of drugs has revolutionized the treatment of hypercholesterolemia. Statins are highly efficacious and very well tolerated. Thus, other drugs are often not needed for low-density lipoprotein cholesterol (LDL-C) reduction.
Atorvastatin (LIPITOR, ATORLIP, LIPVAS, ATORIS, SORTIS, TORVAST, TORVACARD, TORTALIP, TULIP)

How Does Atorlip Work

Atorlip lowers LDL-C by inhibiting HMG-CoA reductase, the enzyme that regulates the rate-limiting step in cholesterol synthesis. The amount of the next byproduct in the cholesterol synthesis pathway (i.e Mevalonate) is lowered, and, subsequently, cholesterol levels are reduced in hepatic cells
. This, in turn, results in up-regulation of LDL receptors and increased hepatic uptake of LDL from the circulation.

Clinical Efficacy Of Atorlip

Atorlip (Generic Atorvastatin Calcium tablets) is effective at high doses, resulting in as much as a 60% reduction in LDL-C. Moreover, Atorlip has the longest half life among all the statins. Numerous clinical trials have generated conclusive benefits in using Atorlip for the primary prevention of hypercholesterolemia in patients with hypertension.

Atorlip Dosage

Best benefits are obtained with higher doses. Titrate to a maximum of 80 mg/day, starting with 10mg/day. As HMG CoA levels are maximum at night, HS or bedtime dosing is ideal.

Side Effects Of Atorlip

Hypersensitivity and Hepatic impairment are noted. Rhabdomyolysis and Myopathy are also documented. Monitoring long term therapy with LFT’s (liver function tests) seems prudent. Myopathic symptoms dictate monitoring of serum CK (Creatine Kinase) levels. Atorlip is contraindicated in pregnancy.

Other Drugs For Treatment Of High Cholesterol Levels

These are gradually fading into oblivion with the advent of statin (Atorlip) therapy. These include
Resins– Cholestyramine
LPL Activators – Fenofibrate (LOFIBRA)
Cholesterol Absorbtion Inhibitors – Ezetimibe (ZETIA)
TGA Inhibitors – Nicotinic Acid.

Role of Atorlip In Reducing Coronary Heart Disease Risk – CONCLUSION

Atorlip can easily be designated as the champion of cholesterol lowering agents.
Its benefits not only include lower lipid profiles but spill over to cardio protection and lowered coronary heart disease risk. Atorlip is an integral member of the group of drugs used for the treatment of ‘syndrome X’ or the ‘Metabolic syndrome’.