Hypertriglyceridemia: A Review of Clinical Relevance and Treatment Options: Focus on Cerivastatin

Hans-Willi M. Breuer, Abteilung für Innere Medizin, St. Carolus-Krankenhaus Görlitz, Carolusstr. 212, 02827 Görlitz, Germany 

Curr Med Res Opin. 2001;17(1):60-73. 

In This Article

Introduction

Raised triglyceride (TG) levels are found in several types of hyperlipidemia - the most common of these is known as Frederickson Type IIb dyslipidemia. TG level is now thought to be one of several independent lipid parameters that can help in predicting the risk of coronary heart disease (CHD)[1,2,3,4,5,6]. Of the risk stratification guidelines currently in use[7,8,9,10,11,12,13,14,15,16,17,18,19,20] (Tables 1 and 2 ), some concentrate on lowering low-density lipoprotein cholesterol (LDL-C) - this view is now regarded as too simplistic.

Prospective epidemiological studies[1,2,3,4,5,21,22,23,24,25] have shown a wide range of other risk predictors for CHD.Many of these interact to compound and confuse the situation, making it difficult to clarify which are independent risk factors and which are associated with an increase in risk only in association with other factors.

It has become clearer from clinical research over the last few years that elevated plasma TG level is strongly associated with an increased risk of CHD.The most common dyslipidemic abnormality (defined by NCEP-II criteria shown in Table 1 ) in hypertensive subjects was an increased LDL-C (79.2% of the cohort) followed by hypertriglyceridemia (31.7%) and low HDL-C (22.3%)[7]. Hypertension is defined as a blood pressure baseline of 140/90 mm Hg on at least three separate occasions prior to hypertensive therapy. Hypertriglyceridemia is defined as a fasting TG level of > 2.26 mmol/l (> 200 mg/dl) and is recognised as a primary indicator for treatment in type Iib dyslipidemia[13].

Two other types of hypertriglyceridemia characterised by elevated VLDL-C commonly seen in clinical practice are Type III hyperlipoproteinemia(familial dysbetalipoproteinemia), in which the HDLC levels are usually within normal range, and Type IV hypertriglyceridemia (familial hypertriglyceridemia),characterised by normal LDL-C levels. Hypertriglyceridemia,secondary to, or exacerbated by, other medical or environmental factors, such as excess alcohol consumption, is usually of the Type IV pattern. Both Types II and IV dyslipidemias can also be associated with an increased risk of CHD[26].

However, not all individuals with raised TG levels have an increased risk of CHD. Hypertriglyceridemiais also seen in several other types of dyslipidemia,associated with age, diet, lifestyle, and a range of medical conditions, drugs and metabolic disorders. In some of these circumstances other factors protect against the risk of CHD and can minimise or negate the effect of the risk factors present. More research is required to fully elucidate the role of TG, the ways in which it can influence other risk factors and the mechanism of its own more direct role in the atherogenic process.

It is thought that the observed association between high TG levels and CHD may be due to the presence of atherogenic TG-rich particles in plasma such as LDL-C and very low-density lipoprotein cholesterol(VLDL-C) rather than the TGs themselves[6]. Furthermore, raised Tgs elicit modifications in other lipoproteins and in the coagulation system[27,28].

Patients with hypertriglyceridemia have been shown to respond well to dietary control. When dietary methods fail, the use of lipid-lowering drugs, such as 3-hydroxy-3-methlyglutaryl-Coenzyme A (HMG CoA) reductase inhibitors (known as statins), fibrates and nicotinic acid, have been shown to be effective at reducing plasma levels of apo-B-containing lipoproteins in hypertriglyceridemic patients[29,30,31,32,33,34,35,36,37,38]. In addition, there are several large ongoing clinical trials in diabetic patients evaluating the effects of statin monotherapy or statins in combination[39,40]. longer-term end-point clinical trials in this area will establish which type of therapy will be the future for different types of dyslipidemic patients.

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