EDUCATION AND TRAINING

M.D., Cornell University Medical College

Intern/Resident, Harvard Medical Service, Boston City Hospital, Boston, MA 

Endocrinology Fellowship, Northwestern University Medical Center, Chicago, IL

OFFICE ADDRESS

Harborview Medical Center
325 Ninth Avenue
UW Mailbox 359720
Seattle, WA 98104-2499


CURRENT RESEARCH INTERESTS

Research on the mechanisms and efficacy of cardiovascular disease risk reduction in humans using dietary, hormonal and pharmacological interventions is moving from surrogate plasma metabolic markers to include non-invasive measures of vascular anatomy and physiology.  Three investigator-initiated, single center studies are currently underway which provide examples of this approach and offer opportunities for endocrine fellowship training and collaboration:

Diets for Dyslipidemia in the Metabolic Syndrome: (NIH HL083117) (Clinical Trials.gov NCT 003662908). This study examines the lipoprotein, glycemic, inflammatory and vasomotor responses to low or moderate allowable-fat diets in persons with the Metabolic Syndrome.  Diets are prepared at the UW GCRC. Following completion of the controlled feeding stage, subjects follow the second assigned diet for 4 months, preparing their own food as a test of diet efficacy in the free-living condition.  The hypothesis is that the moderate fat diet will have a superior effect on all parameters.

Effects of Fish Oil on Carotid IMT in the Metabolic Syndrome:  (Clinical Trials.gov NCT 00350194). This pilot study addresses the question does fish oil have a direct arterial wall benefit, beyond preventing cardiac arrhythmia.  The target group is the high CVD risk persons with the Metabolic Syndrome.  Metabolic parameters will be examined for changes and association with assessments of IMT diameter.  This study will also examine fish oil effects on myocardial function.

Oral vs. Patch Hormonal Contraceptive Effects on Metabolism and Vascular Reactivity: (Clinical Trials.gov NCT00439972).  The controversy about the vascular effects of female sex hormones relates to both pre and post menopausal settings and to the route of administration of the estrogen.  Some of these issues are addressed in a randomized cross-over comparison of patch vs. oral contraceptive administration. The hypothesis is that patch hormonal contraception has higher systemic estrogen exposure and greater benefit on vascular reactivity than oral administration, but no more than equivalent effect on hepatic clotting factor generation due to the first pass effect of the oral form on hepatic clotting factor generation.  The vascular impact of the systemic vs. oral routes of administration is measured by assessing brachial artery reactivity by ultrasound and by forearm venous plethysmography. A sub-study will examine for differential effects of insulin resistance on these parameters.


REPRESENTATIVE PUBLICATIONS

Knopp RH, Walden CE, Retzlaff BM, McCann BS, Dowdy AA, Albers JJ, Gey GO, Cooper MN:  Long-term cholesterol lowering effects of four different fat restricted diets in hypercholesterolemic and combined hyperlipidemic men: The Dietary Alternatives Study. JAMA 278:1509-1515, 1997.

Knopp RH: Drug treatment of lipid disorders. N Engl J Med 341:498-511, 1999.

Walden CE, Retzlaff BM, Buck Bl, Wallick S, McCann BS, Knopp RH:  Differential effect of NCEP diet on HDL-C, its subfractions and apoprotein A-I levels in hypercholesterolemic women and men after one year: the BeFIT study. Arterioscler Thromb Vasc Biol.20:1580-87, 2000.

Knopp RH, Retzlaff B, Fish B, Walden C, Wallick S, Anderson M, Aikawa K Kahn SE:  Effects of insulin resistance and obesity on lipoproteins and sensitivity to egg feeding. Arterioscler Thromb Vasc Biol 23:1437-1443, 2003.

Knopp RH, Retzlaff BM:  Saturated fat prevents coronary artery disease? An American paradox.  Am J Clin Nutr 80:1102-3, 2004.

Knopp RH, Paramsothy P, Retzlaff BM, Fish B, Walden C, Dowdy A, Tsunehara C, Aikawa K, Cheung M:  Gender differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. Current Atherosclerosis Reports 7:472-479, 2005.

Knopp RH, d'Emden M, Smilde JG, Pocock SJ:  Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN).  Diabetes Care 29:1478-85, 2006.

Knopp RH, Fish B, Dowdy A, Retzlaff B, Walden C, Rusanu I, Paramsothy P:  Moderate fat diet for combined hyperlipidemia and the metabolic syndrome. Curr Atheroscler Rep 8:492-500, 2006.

Knopp RH, Tsunehara C, Retzlaff BM, Fish B, Nguyen H, Anderson S, Nguyen T:  Lipoprotein effects of combined ezetimibe and colesevelam hydrochloride versus ezetimibe alone in hypercholesterolemic subjects: A Pilot Study.  Metabolism 55:1697-1703, 2006.

McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, McGovern ME:  Comparative effects on lipid levels combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Atherosclerosis 192:432-437, 2007.