Hyperlipidemias: Capuzzi DM

Morgan JM, Capuzzi DM. · Jefferson Medical College, Thomas Jefferson University, Cardiovascular Disease Prevention Center, Jefferson Heart Institute, Philadelphia, USA. · Geriatrics. · Pubmed #12938250 No free full text.

Abstract: Coronary heart disease (CHD) is a significant cause of morbidity and mortality in older patients. Therefore, its treatment and prevention is vital to improving the length and quality of life for the geriatric population at large. Clinical trial data have demonstrated that patients age 65 and older derive the same benefit from blood cholesterol reduction as younger adults. As a result, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) recommends appropriate therapeutic lifestyle changes and drug therapy for older individuals with established CHD or for those at high risk for CHD. Drug therapy in this population, while safe, requires careful monitoring and dose adjustment due to potentially altered drug metabolism and concomitant medications. These factors lead to use of lower starting doses of lipid-lowering medications in older patients. Prudent individualized evaluation and customized therapy provide optimal cardiovascular outcomes.

Morgan JM, Carey CM, Lincoff A, Capuzzi DM. · Thomas Jefferson University, Jefferson Heart Institute, Sidney Kimmel Laboratory for Preventive Medicine, 925 Chestnut Street, 1st Floor, Philadelphia, PA 19107, USA. · Prev Cardiol. · Pubmed #15539965 No free full text.

Abstract: 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.

Capuzzi DM, Morgan JM, Brusco OA, Intenzo CM. · Cardiovascular Disease Prevention Center, 211 S. 9th Street, Walnut Towers Suite 602, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. · Curr Atheroscler Rep. · Pubmed #11122726 No free full text.

Abstract: Because of the original observation by Altschul et al., that nicotinic acid (niacin), not nicotinamide, in pharmacologic doses lowered human serum cholesterol levels, an avalanche of reports have been published over the past 45 years on the plasma lipid-regulating properties of this drug and its beneficial cardiovascular effects. A myriad of studies that have examined efficacy, safety, adverse effects, and pharmacologic properties of niacin rendered convincing evidence that niacin, used alone or combined with other agents, has favorable effects on serum lipoprotein regulation and on containment of atherothrombotic cardiovascular diseases. However, because of the unusual side effect profile of niacin and the availability of various formulations of this drug, niacin must be used prudently and with careful instruction and monitoring of patients. This review summarizes the pertinent and recent literature on niacin that impacts its therapeutic use. We also discuss some controversial issues and personal clinical experience and opinions on this topic.

Capuzzi DM, Morgan JM, Carey CM, Intenzo C, Tulenko T, Kearney D, Walker K, Cressman MD. · Department of Medicine, Cardiovascular Disease Prevention Center, Jefferson Heart Institute, Thomas Jefferson University, 925 Chestnut Street, 1st Floor, Philadelphia, PA 19107, USA. · Prev Cardiol. · Pubmed #15539964 No free full text.

Abstract: Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged > or =18 years with fasting levels of total cholesterol > or =200 mg/dL, HDL cholesterol > or =45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B > or =110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia.

Capuzzi DM, Morgan JM, Weiss RJ, Chitra RR, Hutchinson HG, Cressman MD. · Thomas Jefferson University, Philadelphia, Pennsylvania, USA. · Am J Cardiol. · Pubmed #12767421 No free full text.

Abstract: Patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels may benefit from combination therapy with a statin and niacin; therefore, we assessed the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia. Men and women > or =18 years with fasting total cholesterol levels > or =200 mg/dl, triglycerides 200 to 800 mg/dl, apolipoprotein B > or cf=110 mg/dl, and HDL cholesterol <45 mg/dl were randomized to 1 of 4 treatments in this 24-week, open-label, multicenter trial: rosuvastatin 10 to 40 mg; ER niacin 0.5 to 2 g; rosuvastatin 40 mg/ER niacin 0.5 to 1 g; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and other lipid measurements at week 24 were determined by analysis of variance, with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group. Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g (-48% vs -0.1% and -36% for LDL cholesterol and -49% vs -11% and -38% for non-HDL cholesterol, respectively; p <0.01 for all comparisons); no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g (-42% and -47%; p = NS). Triglyceride reductions ranged from -21% (ER niacin monotherapy) to -39% (rosuvastatin 40 mg/ER niacin 1 g), but no observed differences were statistically significant. Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol (11% vs 24%, p <0.001) and apolipoprotein A-I (5% vs 11%, p <0.017). Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups. Over 24 weeks, rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin.

Morgan JM, Horton K, Reese D, Carey C, Walker K, Capuzzi DM. · Department of Medicine, Thomas Jefferson University, Philadelphia, Pa 19107, USA. · Int J Vitam Nutr Res. · Pubmed #12463111 No free full text.

Abstract: Serum components, such as lipoproteins, coagulation factors (factor VII, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), fibrinogen), and homocysteine have been associated with cardiovascular disease. Dietary intervention with a low-fat, low-cholesterol diet has favorably influenced cardiovascular disease and certain food, specifically the consumption of nuts, has been associated with reduced cardiovascular risks. The effects of walnuts, as part of a low-fat, low-cholesterol diet, on serum cardiovascular risk factors were determined. Sixty-seven (67) outpatients with borderline high total cholesterol following a low-fat, low-cholesterol diet for six weeks before being randomly assigned to continue the diet or have 64 grams/day of walnuts in conjunction with the diet. After six weeks, the patients' diets were switched. Therefore, all patients consumed 64 grams/day of walnuts for six weeks during part of the trial as part of a low-fat, low cholesterol diet. Serum lipids demonstrated a significant reduction in triacyglycerols and favorable trend with decreases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and a slight increase in high-density lipoprotein (HDL) cholesterol. No statistical effects on homocysteine or the coagulation factors were observed. However, there was a slight favorable trend for tPA and PAI-1. This study demonstrated that walnuts, when consumed as part of a low fat, low-cholesterol diet, have a beneficial effect on serum cardiovascular risk factors. However, these changes may not explain all of the beneficial effects that walnut consumption has on cardiovascular disease.

Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. · Cooper Institute, Dallas, Texas 75230, USA. · Am J Cardiol. · Pubmed #10867091 No free full text.

Abstract: This study compares the effect of plant stanol ester spread with a placebo spread on cholesterol in patients taking statin therapy, but who still had elevated low-density lipoprotein (LDL) cholesterol. This was a randomized, double-blind, placebo-controlled clinical trial, with 67 women and 100 men with LDL cholesterol >/=130 mg/dl and triglycerides </=350 mg/dl who had been taking a stable dose of a statin drug for at least 90 days before the start of the study. For 8 weeks, participants consumed 3 servings/day of the plant stanol ester spread that provided 5.1 g/day of plant stanol ester or a placebo. The addition of plant stanol ester spread significantly reduced total cholesterol and LDL cholesterol at 2, 4, and 8 weeks when compared with placebo spread. Plant stanol ester spread reduced total cholesterol at 8 weeks by 12% compared with a placebo reduction of 5% (-7% difference; p <0.0001). Plant stanol ester spread reduced LDL cholesterol at 8 weeks by 17% compared with a 7% reduction in the placebo group (-10% difference, p <0.0001). The absolute reduction in LDL cholesterol at 8 weeks was 24 and 10 mg/dl in the stanol ester and placebo groups, respectively. The plant stanol ester spread group also had greater reductions in both serum total cholesterol and LDL cholesterol than the placebo group at 2 and 4 weeks (p <0.001 for all comparisons). Both spreads were well tolerated by study participants, and no significant adverse events were noted. Consumption of spread that provided 5.1 g/day of plant stanol esters effectively reduced elevated total and LDL cholesterol levels in participants on a stable regimen of a statin.

Goldberg A, Alagona P, Capuzzi DM, Guyton J, Morgan JM, Rodgers J, Sachson R, Samuel P. · Lipid Research Clinic, Washington University School of Medicine, St. Louis, MO 63110, USA. · Am J Cardiol. · Pubmed #10781759 No free full text.

Abstract: This multicenter trial evaluated the safety and efficacy of escalating doses of Niaspan (niacin extended-release tablets) and placebo (administered once-a-day at bedtime) in patients with primary hyperlipidemia on the percent change from baseline in levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Extended-release niacin was initiated at a dose of 375 mg/day, raised to 500 mg/day, and further increased in 500-mg increments at 4-week intervals to a maximum of 3,000 mg/day. A total of 131 patients (n = 87, extended-release niacin; n = 44, placebo) were treated for 25 weeks with study medication after a 6-week diet lead-in/drug washout phase and 2-week baseline LDL cholesterol stability phase. Significant decreases from baseline in levels of LDL cholesterol and apolipoprotein B became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or =0. 05), reaching 21% and 20%, respectively, at the 3,000-mg/day dose. Significant increases from baseline in levels of high-density lipoprotein cholesterol became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or = 0.05), reaching 30% at the 3,000-mg dose. Significant decreases from baseline in triglycerides and lipoprotein(a) occurred at the 1,000-mg dose and were apparent at all subsequent doses (p < or =0.05), reaching 44% and 26%, respectively, at the 3,000-mg dose. The most common adverse events were flushing and gastrointestinal disturbance. Transaminase increases were relatively small, and the proportion of patients who developed liver function abnormalities on extended-release niacin was not significantly different from placebo. Thus, extended-release niacin was generally well tolerated and demonstrated a dose-related ability to alter favorably most elements of the lipid profile.

Lu Z, Kou W, Du B, Wu Y, Zhao S, Brusco OA, Morgan JM, Capuzzi DM, Anonymous00319, Li S. · Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, Peoples Republic of China. · Am J Cardiol. · Pubmed #18549841 No free full text.

Abstract: Results of well-controlled prospective clinical trials showed the efficacy of lipid-lowering therapies in the reduction of cardiovascular (CV) events in western populations, but they were not reported with a Chinese population. This multicenter study was conducted to determine the effects of Xuezhikang (XZK), a partially purified extract of red yeast rice, on lipoprotein and CV end points in Chinese patients who experienced a previous myocardial infarction. Nearly 5,000 of these patients with average low-density lipoprotein cholesterol levels at baseline were randomly assigned either to placebo or to XZK daily for an average of 4.5 years. The primary end point was a major coronary event that included nonfatal myocardial infarction and death from coronary heart disease. Frequencies of the primary end point were 10.4% in the placebo group and 5.7% in the XZK-treated group, with absolute and relative decreases of 4.7% and 45%, respectively. Treatment with XZK also significantly decreased CV and total mortality by 30% and 33%, the need for coronary revascularization by 1/3, and lowered total and low-density lipoprotein cholesterol and triglycerides, but raised high-density lipoprotein cholesterol levels. In conclusion, long-term therapy with XZK significantly decreased the recurrence of coronary events and the occurrence of new CV events and deaths, improved lipoprotein regulation, and was safe and well tolerated.