1.
Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia.
Stein, EA, Honarpour, N, Wasserman, SM, Xu, F, Scott, R, Raal, FJ
Circulation. 2013;(19):2113-20
Abstract
BACKGROUND Homozygous familial hypercholesterolemia is a rare, serious disorder with a substantial reduction in low-density lipoprotein (LDL) receptor function, severely elevated LDL cholesterol, cardiovascular disease, and often death in childhood. Response to conventional drug therapies is modest. Monoclonal antibodies to proprotein convertase subtilisin/kexin 9 (PCSK9) reduce LDL cholesterol in heterozygous familial hypercholesterolemia. The effect in homozygous familial hypercholesterolemia is unknown and uncertain. We evaluated the efficacy and safety of AMG 145 in an open-label, single-arm, multicenter, dose-scheduling pilot study in patients with homozygous familial hypercholesterolemia. METHODS AND RESULTS Eight patients with LDL receptor-negative or -defective homozygous familial hypercholesterolemia on stable drug therapy were treated with subcutaneous 420 mg AMG 145 every 4 weeks for ≥12 weeks, followed by 420 mg AMG 145 every 2 weeks for an additional 12 weeks. All patients completed both treatment periods. Mean change from baseline in LDL cholesterol at week 12 was -16.5% (range, 5.2% to -43.6%; P=0.0781) and -13.9% (range, 39.9% to -43.3%; P=0.1484) with 4- and 2-week dosing, respectively. No reduction was seen in the 2 receptor-negative patients. Over the treatment periods, mean±SD LDL cholesterol reductions in the 6 LDL receptor-defective patients were 19.3±16% and 26.3±20% with 4- and 2-week dosing, respectively (P=0.0313 for both values), ranging from 4% to 48% with 2-week dosing. No serious side effects were reported. CONCLUSION This study demonstrates significant and dose-related LDL cholesterol lowering with a PCSK9 monoclonal antibody in homozygous familial hypercholesterolemia patients with defective LDL receptor activity but no reduction in those who were receptor negative.
2.
Effects of the addition of t'ai chi to a dietary weight loss program on lipoprotein atherogenicity in obese older women.
Beebe, N, Magnanti, S, Katkowski, L, Benson, M, Xu, F, Delmonico, MJ, Lofgren, IE
Journal of alternative and complementary medicine (New York, N.Y.). 2013;(9):759-66
Abstract
OBJECTIVE To examine the additive effect of t'ai chi (TC) to diet education on the traditional coronary heart disease (CHD) risk factor low-density lipoprotein cholesterol (LDL-C) and on emerging CHD risk factors (apolipoprotein B and LDL particle size) in older obese women. DESIGN Ancillary study of a randomized clinical trial. SETTING University of Rhode Island. PARTICIPANTS 26 obese women (mean age±standard deviation, 61.5±6.0 years; mean body mass index, 34.3±4.0 kg/m(2)) were enrolled and randomly assigned to the diet education group (n=13) or the diet education plus TC group (n=13). INTERVENTION All participants received 45 minutes of diet education per week. The diet education plus TC group also received 45 minutes of TC three times per week for 16 weeks. OUTCOME MEASURES Anthropometrics (height, weight, BMI, waist circumference, and hip circumference), clinical variables (blood pressure), and biochemical variables (standard lipid profile, apolipoprotein B, LDL particle size) were measured. The primary outcome was LDL-C, and the secondary outcomes were apolipoprotein B and LDL particle size. RESULTS Neither LDL-C nor apolipoprotein B improved in either group. Percentage of large LDL particles after the intervention was increased in the diet education plus TC group compared with the diet education group. Weight, waist circumference, and high-density lipoprotein cholesterol decreased in both groups from baseline to post-intervention. Triacylglycerol and dietary screening tool scores increased in both groups. Additional improvements were seen in the diet education plus TC group, including a significant increase in Dietary Approaches to Stop Hypertension score from baseline to post-intervention. CONCLUSION The addition of TC to diet education is more effective than diet education alone at improving diet quality and emerging CHD risk factors, such as LDL particle size, in obese older women.