Niacin-ER/statin combination for the treatment of dyslipidemia: focus on low high-density lipoprotein cholesterol

Statins are effective drugs for lowering low-density lipoprotein cholesterol, and their use has been associated with a significant decrease in cardiovascular morbidity and mortality. However, statins are ineffective in lowering plasma triglycerides and lipoprotein(a), or increasing low high-density lipoprotein cholesterol (HDL-C) plasma levels, which are independent risk factors for coronary heart disease. Niacin, on the other hand, is the most potent drug available for lowering plasma levels of triglycerides and lipoprotein(a) and raising HDL-C levels. It follows, then, that a combination of niacin with a statin might be an effective combination in improving all components of the lipid profile. Previous studies have shown that the use of long-acting niacin with a statin, in dose combinations of niacin-ER/lovastatin 1000/20 mg or 2000/40 mg once daily, has been effective in favorably modifying low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), and HDL-C plasma levels. Dyslipidemias often predate the onset of hypertension, and HDL-C has been found to be inversely related to the incidence of hypertension. Normalization of lipid components, including the total cholesterol/HDL-C ratio, is important in the management of hypertensive individuals and patients with the metabolic syndrome or diabetes. Thus, the long-term treatment of dyslipidemias with these two agents may help to modify risk and reduce cardiovascular morbidity and mortality in these patients over and above benefits achieved by lowering blood pressure     

Combination niacin and statin therapy in primary and secondary prevention of cardiovascular disease

Statin monotherapy may not be sufficient to reach serum lipid goals in many patients, especially in those with combined lipid abnormalities. Statins cause only a modest increase in high-density lipoprotein cholesterol (HDL)--an established independent protective factor for coronary heart disease (CHD)--and a modest decrease in triglycerides (TG). Niacin is an effective pharmacologic agent for increasing HDL, as well as lowering TG. Used in combination with a statin, niacin provides an option to help patients attain their low-density lipoprotein cholesterol (LDL-C) goals, non-HDL goals, and HDL goals. Based on the National Health and Nutrition Examination Survey, 1999 to 2000, only 12% of the surveyed adult population were under treatment for diagnosed hypercholesterolemia. Furthermore, only 5.4% of the surveyed population had attained goal total cholesterol levels of < 5.2 mmol/I (< 200 mg/dl). Combination therapy offers a means to get more people to goal. This paper reviews the impact of lipid-modifying combination therapy with niacin plus a statin on lipid profile outcomes.     

Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis

BACKGROUND: Combination therapy to improve the total lipid profile may achieve greater coronary risk reductions than lowering low-density lipoprotein cholesterol (LDL-C) alone. A new extended-release niacin (niacin ER)/lovastatin tablet substantially lowers LDL-C, triglyceride, and lipoprotein(a) levels and raises high-density lipoprotein cholesterol (HDL-C) level. We evaluated these serum lipid responses to niacin ER/lovastatin at all clinically reasonable doses. METHODS: Men (n = 85) and women (n = 79) with type IIa or IIb primary hyperlipidemia after diet were randomized among 5 parallel treatment arms. Each arm had 5 sequential 4-week treatment periods: niacin ER (starting at 500 mg/d, increasing in 500-mg increments to 2500 mg/d); lovastatin (starting at 10 mg, increasing to 20 mg, then 40 mg/d); and 3 combinations arms, each with a constant lovastatin dose and escalating niacin ER doses. RESULTS: For primary comparisons, mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin (1500/20 mg) than with lovastatin (20 mg) (35% vs 22%, P<.001) and with niacin ER/lovastatin (2000/40 mg) than with lovastatin (40 mg) (46% vs 24%, P<.001). Each 500-mg increase in niacin ER, on average, decreased LDL-C levels an additional 4% and increased HDL-C levels 8%. The maximum recommended dose (2000/40 mg/d) increased HDL-C levels 29% and decreased LDL-C levels 46%, triglyceride levels 38%, and lipoprotein(a) levels 14%. All lipid responses were dose dependent and generally additive. Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses. CONCLUSIONS: Niacin ER/lovastatin combination therapy substantially improves 4 major lipoprotein levels associated with atherosclerotic disease. Dose-response surfaces provide a practical guide for dose selection.     

Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease

In this study, niacin was added to existing therapy for 3 months in 54 subjects with stable coronary artery disease. Average total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were similar between groups. Three months of niacin treatment increased total HDL by 7.5% and decreased triglycerides by 15% compared with baseline values (p <0.005 for each), whereas total cholesterol and LDL levels remained unchanged. Addition of niacin resulted in a 32% increase in large-particle HDL (p <0.001), an 8% decrease in small-particle HDL (p = 0.0032), an 82% increase in large-particle LDL (p = 0.09), and a 12% decrease in small-particle LDL (p = 0.008). Niacin decreased lipoprotein-associated phospholipase A2 and C-reactive protein levels (20% and 15%, respectively, p <0.05 for the 2 comparisons). No significant changes from baseline were seen in any tested parameter in subjects who received placebo. In conclusion, addition of niacin to existing medical regimens for patients with coronary artery disease and already well-controlled LDL levels favorably improves the distribution of lipoprotein particle sizes and inflammatory markers in a manner that would be expected to confer atheroprotection. The effect of altering lipoprotein particle distribution and inflammatory markers on surrogate markers of atherosclerosis and clinical cardiovascular events in this population remains unclear.     

Niacin: The Evidence,Clinical Use,and Future Directions

The use of FDA-approved niacin (nicotinic acid or vitamin B3) formulations at therapeutic doses, alone or in combination with statins or other lipid therapies, is safe, improves multiple lipid parameters, and reduces atherosclerosis progression. Niacin is unique as the most potent available lipid therapy to increase high-density lipoprotein (HDL) cholesterol and it significantly reduces lipoprotein(a). Through its action on the GPR109A receptor, niacin may also exert beneficial pleiotropic effects independent of changes in lipid levels, such as improving endothelial function and attenuating vascular inflammation. Studies evaluating the impact of niacin in statin-naïve patients on cardiovascular outcomes, or alone and in combination with statins or other lipid therapies on atherosclerosis progression, have been universally favorable. However, the widespread use of niacin to treat residual lipid abnormalities such as low HDL cholesterol, when used in combination with statins among patients achieving very low (<75 mg/dL) low-density lipoprotein cholesterol levels, is currently not supported by clinical outcome trials.     

HDL and CETP Inhibition: Will This DEFINE the Future?

OPINION STATEMENT: The premature stopping of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health) study due to futility has called into question the clinical value of high-density lipoprotein cholesterol (HDL-C) increases. The failure of estrogen therapy in the HERS (Heart and Estrogen/progestin Replacement Study) trial and the cholesteryl ester transfer protein (CETP) inhibitors torcetrapib (in the ILLUMINATE [Investigation of Lipid Level Management to Understand Its Impact in Atherosclerotic Events] trial) and, most recently, dalcetrapib in the dal-OUTCOMES trial has cast doubt on the "HDL-raising hypothesis" for providing additional benefits on top of statin therapy. The AIM-HIGH trial was designed to equalize low-density lipoprotein cholesterol (LDL-C) levels between the two treatment groups while the niacin arm would have a higher HDL-C. The study population included patients with low HDL-C and cardiovascular disease (CVD); because this population has a high residual risk for CVD on statin therapy, these patients were most likely to benefit from the niacin HDL-C-raising effect. These findings are disappointing because clinicians have used extended-release niacin to treat patients with low HDL-C because niacin has demonstrated benefit in earlier reported studies in conjunction with statins and other drugs, as observed in the Cholesterol Lowering Atherosclerosis Study (CLAS) and the HDL-Atherosclerosis Treatment Study (HATS). In the Coronary Drug Project, niacin alone was shown to reduce myocardial infarction, stroke, and the need for coronary bypass surgery. Niacin does not increase the number of HDL particles to the same extent it raises HDL-C. Niacin alters the composition of HDL, making the particle larger, which is similar to the effects of CETP inhibition on HDL. Both niacin and CETP inhibitors decrease the catabolism of HDL, thereby increasing the size of the HDL particle and raising HDL-C. Dalcetrapib, which does not decrease LDL-C while raising HDL-C, was recently discontinued from clinical development due to a interim analysis that determined that the study was futile. Anacetrapib, which markedly increases HDL-C while also significantly lowering LDL-C, remains in clinical development, with a large cardiovascular end point trial currently enrolling 30,000 high-risk patients. For now, the goal remains the achievement of LDL-C and non-HDL targets, and low HDL-c remains a significant independent risk factor, but there is insufficient evidence that raising HDL-C will provide a clinical benefit.     

The high-fat high-fructose hamster as an animal model for niacin’s biological activities in humans

ObjectiveNiacin has been used for more than 50 years to treat dyslipidemia, yet the mechanisms underlying its lipid-modifying effects remain unknown, a situation stemming at least in part from a lack of validated animal models. The objective of this study was to determine if the dyslipidemic hamster could serve as such a model.Materials/MethodsDyslipidemia was induced in Golden Syrian hamsters by feeding them a high-fat, high-cholesterol, and high-fructose (HF/HF) diet. The effect of high-dose niacin treatment for 18 days and 28 days on plasma lipid levels and gene expression was measured.ResultsNiacin treatment produced significant decreases in plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and free fatty acids (FFA), but had no measureable effect on high-density lipoprotein cholesterol (HDL-C) in the dyslipidemic hamster. Niacin treatment also produced significant increases in hepatic adenosine ATP-Binding Cassette A1 (ABCA1) mRNA, ABCA1 protein, apolipoprotein A-I (Apo A-I) mRNA, and adipose adiponectin mRNA in these animals.ConclusionsWith the exception of HDL-C, the lipid effects of niacin treatment in the dyslipidemic hamster closely parallel those observed in humans. Moreover, the effects of niacin treatment on gene expression of hepatic proteins related to HDL metabolism are similar to those observed in human cells in culture. The HF/HF-fed hamster could therefore serve as an animal model for niacin’s lowering of proatherogenic lipids and mechanisms of action relative to lipid metabolism.     

他汀类和烟酸类降脂药物联合应用治疗心血管疾病

单独使用他汀类降脂药治疗时,许多患者的血浆脂蛋白达不到治疗目标,尤其是在多项血脂不正常的患者中,他汀类只能轻度的增高高密度脂蛋白(HDL-C):一种独立预测冠心病的因素和轻度的降低甘油三酯(TG)的作用。烟酸对增高HDL和降低TG有明显的药理作用。他汀类和烟酸类合用可以帮助患者控制低密度脂蛋白胆固醇(LDL-C)和升高HDL-C。     

A dose-ranging study of a new,once-daily,dual-component drug product containing niacin extended-release and lovastatin

BACKGROUND: Combination therapy for dyslipidemia holds promise as effective treatment for patients with multiple lipid disorders, especially those at high risk. HYPOTHESIS: This study evaluated dose-response relationships and safety of a new dual-component drug product containing niacin extended-release (niacin ER) and lovastatin. METHODS: The 28-week double-blind multicenter trial randomized 237 patients with type IIA or IIB hyperlipidemia to one of four escalating-dose treatment groups: niacin ER/lovastatin 1,000/20 mg, niacin ER/lovastatin 2,000/40 mg, niacin ER 2,000 mg, or lovastatin 40 mg. RESULTS: Niacin ER/lovastatin was more effective than each of its components for improving levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), and exhibited a clear dose-response effect and additivity across the dosage range. The 2,000/40 dose achieved greater mean reductions in LDL-C (-42%) than 1,000/20 (-28%, p < 0.001), lovastatin 40 mg (-32%, p < 0.05), or niacin ER 2,000 mg (-14%, p < 0.05). The 2,000/40 dose was significantly more effective in increasing HDL-C levels (+30%) than the 1,000/20 dose (+21%, p = 0.016). The decrease in TG was greater with 2,000/40 (-43%) than with 1,000/20 (-26%, p = 0.009). All three niacin-containing treatments were more effective than lovastatin monotherapy in reducing lipoprotein (a) [Lp(a)] levels. Flushing caused 12 (11%) patients receiving niacin ER/lovastatin and I patient receiving lovastatin alone to withdraw. No drug-related myopathy was noted. One patient each in the 2,000/40 group and the lovastatin 40-mg group had reversible elevations in liver transaminases. CONCLUSIONS: Niacin ER/lovastatin is well tolerated and effective for patients with multiple lipid disorders.     

Niacin: another look at an underutilized lipid-lowering medication

Niacin, or water-soluble vitamin B(3), when given at pharmacologic doses, is a powerful lipid-altering agent. This drug, which lowers the levels of atherogenic, apolipoprotein-B-containing lipoproteins, is one of few medications that can raise the levels of atheroprotective HDL cholesterol. Niacin also has beneficial effects on other cardiovascular risk factors, including lipoprotein(a), C-reactive protein, platelet-activating factor acetylhydrolase, plasminogen activator inhibitor 1 and fibrinogen. Many clinical trials have confirmed the lipid effects of niacin treatment; however, its effects on cardiovascular outcomes have been called into question owing to the AIM-HIGH trial, which showed no benefit of niacin therapy on cardiovascular endpoints. Furthermore, use of niacin has historically been limited by tolerability issues. In addition to flushing, worsened hyperglycaemia among patients with diabetes mellitus has also been a concern with niacin therapy. This article reviews the utility of niacin including its mechanism of action, clinical trial data regarding cardiovascular outcomes, adverse effect profile and strategies to address these effects and improve compliance.     

Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio

Niacin significantly alters blood lipid concentrations but its use has been limited because of clinically disturbing side effects. In an attempt to circumvent these drawbacks, 55 patients with cardiovascular disease were given low-dose long-acting niacin, 1 g/d. Treatment was continued for a mean of 6.7 months and lipid values were compared with a non-treated group of 17 patients followed for a mean of 6.3 months. Lipid values did not change in the nontreated group. In the niacin-treated group total cholesterol and triglyceride levels also did not significantly change. High-density lipoprotein (HDL) cholesterol level rose 31% from 1.01 +/- 0.31 mmol/L to 1.32 +/- 0.31 mmol/L and total cholesterol/HDL cholesterol ratio was reduced 27% from 6.4 +/- 1.9 to 4.7 +/- 1.3. Despite these results, 40% of the patients left the study mainly because of side effects. Apart from one patient who developed overt diabetes, of questionable relationship to niacin, no patient developed serious side effects such as jaundice or peptic ulcer as seen with much higher doses of the drug. Although often difficult to administer to patients, niacin, particularly in low dose, deserves consideration as an inexpensive agent especially useful for elevating HDL cholesterol level and altering the total cholesterol/HDL cholesterol ratio.     

Postprandial lipemia and associated metabolic disturbances in healthy and hyperlipemic postmenopausal women

The increased risk for coronary artery disease observed in postmenopausal women is partly explained by a more atherogenic fasting lipoprotein profile. Moreover, natural menopause has been associated with an altered postprandial lipid profile. To better characterize the interaction between fasting and postprandial lipid profile after menopause, we examined postprandial changes in several lipid parameters in three age-matched groups of postmenopausal women (16 affected by mixed hyperlipemia, 17 by common hypercholesterolemia, and 17 normolipemic), who underwent a standardized oral fat-loading test. The magnitude of postprandial lipemia, expressed as 8-hour triglyceride incremental area under the curve, was greater in women with mixed hyperlipemia (1,326 +/- 372 mg x dL(-1) x h(-1)) than in normal (484 +/- 384 mg x dL(-1) x h(-1)) and hypercholesterolemic (473 +/- 223 mg x dL(-1) x h(-1); both P <.0001) women, and the differences held after adjustment for body mass index and fasting insulin. Women with mixed hyperlipemia showed a significant postprandial decrease in high-density lipoprotein 2 (HDL(2)) cholesterol, lipoprotein (a), and low-density lipoprotein (LDL) particle size. Both hypercholesterolemic and normolipemic women showed a significant postprandial decrease in HDL cholesterol and lipoprotein (a) levels but not in LDL size. In a multiple linear regression analysis, fasting triglyceride levels, insulin level, and waist-hip ratio were all independent predictors of the magnitude of postprandial lipemia. In conclusion, postmenopausal women with mixed hyperlipemia show a greater postprandial triglyceride increase and a more pronounced reduction in HDL cholesterol level and LDL size than hypercholesterolemic and normolipemic subjects. The presence of the features of insulin resistance syndrome could contribute to the deterioration of postprandial lipemic response in these subjects.     

Treatment of dyslipidemia: how and when to combine lipid lowering drugs

Familial combined hyperlipidemia (FCH) is a frequent familial lipid disorder associated with insulin resistance, low HDL cholesterol, high triglycerides and cholesterol levels with variable phenotypes within the same family. FCH is linked to a high risk for cardiovascular diseases. Treatment goals for lipid abnormalities are changing in recent years. Lowering elevated levels of LDL e Non HDL-cholesterol levels are primary targets of therapy. Lower LDL-C than 70 mg/dL seems to be useful to lower cardiovascular risk in patients with very high risk. Many statins are available, with different potencies and drug interactions. Combination therapy of statins and bile acid sequestrants or ezitimibe may be necessary to further decrease LDL cholesterol levels in order to meet guideline goals. High triglycerides and low HDL cholesterol are also important goals in the treatment of these patients, and frequently statins alone are insufficient to normalize the lipid profile. Combination therapy with fibrates will further lower triglycerides and increase HDL cholesterol levels; this combination is also associated with higher incidence of myopathy and liver toxicity; appropriate evaluation of patients' risk and benefits is necessary. Association of statin/niacin seems be very useful in patients with FCH, especially as niacin is the best drug to increase HDL cholesterol; this association is not linked to a higher frequency of myopathy. Niacin causes flushing, that can in part be managed with use of aspirin and extended release forms (Niaspan); niacin also may increase plasma glucose and uric acid levels. Evaluation of risks and benefits for each patient is needed.     

Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin

To minimize the cutaneous flushing symptoms associated with niacin use, a time-release capsule form of niacin has been formulated. Thus study compares the effects of time-release niacin with those of unmodified niacin on lipoprotein lipids, including HDL2 and HDL3, apoproteins A-I and A-II, clinical chemistries, symptomatic side effects, and adherence to the medication regimen. Seventy-one primarily hypercholesterolemic subjects were randomized to either unmodified niacin or time-release niacin ad took medication for a six-month period. The two groups were closely matched on anthropomorphic and lipid variables. Adherence to the therapeutic regimen at a dose of 1.5 g/d in the first month of treatment was similar in the two groups. Thereafter, at a dose of 3.0 g/d, adherence was in excess of 90% among subjects taking unmodified niacin but only 64% among those taking time-release niacin, chiefly because of aggravated gastrointestinal symptoms; cutaneous flushing side effects, however, were slightly less common with time-release niacin. At these levels of adherence, LDL cholesterol (C) was reduced 21% by unmodified niacin and 13% by the time release form. Plasma total triglyceride was reduced more with unmodified niacin (27%) than with time-release niacin (8% maximum), and HDL-C and HDL2-C were increased significantly with unmodified niacin (26% and 36%) and were not significantly changed by time-release niacin. Increased to a similar degree on both regimens were HDL3-C (approximately 35%) and apoA-I (approximately 12%). ApoA-II was not affected by either drug regimen.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of niacin on lipoprotein subclass distribution

Dyslipidemia is a heterogeneous metabolic condition; high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein represent families of lipoprotein particles that differ in size and composition and vary in atherogenicity. Lipoprotein subclasses containing apolipoprotein B promote atherosclerosis, of which the most atherogenic appear to be the small, dense LDL and large very-low-density lipoprotein subclasses, while the large HDL2 subclass, which transports esterified cholesterol from the periphery to the liver, is considered the more cardioprotective. Niacin has long been known to improve concentrations of all major lipids and lipoproteins, but it also has consistently favorable effects on subclass distribution. A MEDLINE search was conducted for clinical studies reporting the effects of niacin on lipoprotein subclasses. The niacin-associated elevations in HDL cholesterol likely stem from differential drug effects on subclasses, producing favorable changes in levels of HDL2 and apolipoprotein A-I. Niacin has more moderate LDL cholesterol-lowering efficacy, but this change is associated with an increase in LDL particle size and a shift from small LDL to the less atherogenic, large LDL subclasses. In addition, it also tends to decrease concentrations of the larger very-low-density lipoprotein subclasses. Niacin confers diverse benefits with respect to both the quantity and quality of lipid and lipoprotein particles.     

Efficacy and safety of immediate-release niacin in patients with ischemic cardiopathy. Experience of the Instituto Nacional de Cardiología "Ignacio Chávez"

Primary and secondary prevention trials have demonstrated that niacin improves the lipid profile and reduces coronary morbidity and mortality. OBJECTIVE: To investigate the safety and efficacy of niacin in daily doses of 1.5 and 3.0 g in patients with ischemic heart disease and dyslipidemia. PATIENTS AND METHODS: Sixty one male and female patients, aged 30 to 70 years were included. Thirty two patients were later excluded; 18 for adverse events and 14 for causes not related to niacin. RESULTS: In the 29 patients that finished the study, niacin in a dose-dependent manner, significantly reduced the levels of total cholesterol, LDL-cholesterol, triglycerides, apoB and LDL-C/HDL-C ratio, and significantly increased HDL-Cholesterol concentrations; a decrease in lipoprotein(a) was observed with both dosages, but the change was significant only with the 3.0 g/day. In 11 patients (38%) lipids and lipoproteins reached ideal concentrations. In 15 patients (52%) C-LDL/C-HDL was lower than or equal to 3.5 at the end of the study. CONCLUSIONS: Our results suggest that niacin is well tolerated by 62% of the patients. Niacin is a safe, effective and a low cost alternative in the treatment of patients with ischemic heart disease and dyslipidemia.     

Comparison of once-daily,niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin (the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE])

This study compared the relative efficacy of a once-daily niacin extended-release (ER)/lovastatin fixed-dose combination with standard doses of atorvastatin or simvastatin, with a special emphasis on relative starting doses. Subjects (n = 315) with elevated low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol blood levels (defined as LDL cholesterol blood levels > or =160 mg/dl without coronary artery disease, or > or =130 mg/dl if coronary artery disease was present, and HDL cholesterol <45 mg/dl in men and <50 mg/dl in women) were randomized to atorvastatin, simvastatin, or niacin ER/lovastatin for 16 weeks. The primary efficacy variables were the mean percent change in LDL cholesterol and HDL cholesterol levels from baseline. After 8 weeks, the starting dose niacin ER/lovastatin 1,000/40 mg and the 10-mg starting dose atorvastatin both lowered mean LDL cholesterol by 38%. After 12 weeks, niacin ER/lovastatin 1,000/40 mg lowered LDL cholesterol by 42% versus 34% with the 20-mg starting dose of simvastatin (p <0.001). Niacin ER/lovastatin increased HDL cholesterol significantly more than atorvastatin or simvastatin at all compared doses (p <0.001). Niacin ER/lovastatin also provided significant improvements in triglycerides, lipoprotein(a), apolipoprotein A-1, apolipoprotein B, and HDL subfractions. A total of 6% of study subjects receiving niacin ER/lovastatin withdrew because of flushing. No significant differences were seen among study groups in discontinuance due to elevated liver enzymes. No drug-induced myopathy was observed. Niacin ER/lovastatin was comparable to atorvastatin 10 mg and more effective than simvastatin 20 mg in reducing LDL cholesterol, was more effective in increasing HDL cholesterol than either atorvastatin or simvastatin, and provided greater global improvements in non-HDL cholesterol, triglycerides, and lipoprotein(a).     

Factors associated with plasma lipids and lipoproteins in type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIM: To assess the determinants and prevalence of hyperlipidaemia in Type 1 diabetic patients in the EURODIAB IDDM Complications Study. METHODS: Standardized questionnaire data were obtained and anthropometric and biochemical measurements performed on 3159 Type 1 diabetic patients, randomly selected from 31 diabetes clinics. Plasma lipid levels were determined centrally, using enzymatic methods RESULTS: Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), and HDL subfractions were higher in women than in men, while plasma triglycerides were higher in men (P < 0.001). Total cholesterol, low-density lipoprotein cholesterol (LDL-C) and HDL-C and HDL-C subfractions were, as expected, significantly associated with age and HbA1c in both sexes. Age and HbA1c adjusted values of triglyceride, total cholesterol, LDL-C, HDL-C and HDL3-C in men and triglyceride and HDL2-C in women showed significant associations with central obesity, measured as the waist to hip ratio (WHR). Current smokers had lipid profiles characteristic of insulin resistance in comparison to nonsmokers. Significant positive associations were observed between hypertension and plasma triglycerides, total cholesterol and LDL-C in men and women. In men, degree of physical activity was negatively associated with triglyceride and positively related to HDL-C and HDL3-C. The prevalence of LDL-hypercholesterolaemia (LDL-C > 3.35 mmol/L) was 45% in men and in women, while plasma triglyceride levels > 1.7 mmol/L were observed in 12% of men and 8% of women. CONCLUSION: The results of this study indicate that lipid levels in Type 1 diabetic patients are strongly influenced by smoking habit and central obesity in a way that is characteristic of the insulin resistance syndrome.     

Antiatherothrombotic effects of nicotinic acid

Cardiovascular event reduction in hypercholesterolemic subjects appropriately emphasizes the prominent role of statin therapy; however, niacin (nicotinic acid) is also an effective lipid-altering agent that prevents atherosclerosis and reduces cardiovascular events. Niacin has multifarious lipoprotein and anti-atherothrombosis effects that improve endothelial function, reduce inflammation, increase plaque stability, and diminish thrombosis. Niacin reduces the atherogenicity of low-density lipoprotein (LDL) by changing the distribution of small LDL to large LDL subclass, and the susceptibility of LDL to oxidative modification. It is the most effective agent for increasing high-density lipoprotein cholesterol. Moreover, it favorably alters high-density lipoprotein composition, increasing apolipoprotein AI relative to apolipoprotein AII. Niacin reduces blood viscosity through a variety of mechanisms, thus improving blood flow and perfusion through stenotic segments of the vasculature. Finally, niacin has cardioprotective effects that may limit ischemia-reperfusion injury. By preserving glycolysis during periods of ischemia and improving subendocardial blood flow during reperfusion, niacin can improve the functional recovery of the myocardium.     

Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study)

International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides for patients at moderately high to high coronary heart disease (CHD) risk. Combination therapy is often required to achieve multiple lipid treatment goals, and > or =50% reduction in low-density lipoprotein cholesterol (LDL-C) is needed in some patients to achieve aggressive LDL-C targets. In this context, we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin (niacin ER), a statin plus ezetimibe, and a highly potent statin alone. This was an open-label, multicenter, 12-week study in 292 patients (50% women) who qualified for drug therapy based on number of CHD risk factors. Patients were randomized to four parallel arms, titrated from low to moderate or high doses: atorvastatin/niacin ER, rosuvastatin/niacin ER, simvastatin/ezetimibe, or rosuvastatin alone. Baseline mean values were, for LDL-C 197 mg/dL (5.1 mmol/L), HDL-C 49 mg/dL (1.3 mmol/L), triglycerides 168 mg/dL (1.9 mmol/L). There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment. All groups lowered LDL-C by approximately 50% or more (range -49 to -57%), achieving mean levels of 82-98 mg/dL (2.1-2.5 mmol/L). Changes in non-HDL-C (range -46 to -55%) mirrored those for LDL-C and did not differ among treatment groups. Statin/niacin ER combination regimens also increased HDL-C and large HDL (HDL2) and lowered triglycerides and lipoprotein (a) significantly more than other regimens. No drug-related myopathy or hepatotoxicity was observed. In this study, low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD.