|
Sign In to gain access to subscriptions and/or personal tools.
|
Therapeutic Advances in Cardiovascular Disease, Vol. 1, No. 1,
27-35 (2007)
DOI: 10.1177/1753944707082697
© 2007 SAGE Publications
Review: Renin-angiotensin-aldosterone system intervention in the cardiometabolic syndrome and cardio-renal protection
Adam Whaley-Connell
Division of Nephrology, Department of Internal Medicine, University of Missouri Health Sciences Center, One Hospital Dr., MA436, DC 043.0, Columbia MO 65212, whaleyconnella{at}health.missouri.edu
Brian S. Pavey
University of Missouri-Columbia School of Medicine, Departments of Medicine, Physiology, and Pharmacology, Divisions of Endocrinology and Nephrology, Harry S Truman VA Medical Center
Kunal Chaudhary
University of Missouri-Columbia School of Medicine, Departments of Medicine, Physiology, and Pharmacology, Divisions of Endocrinology and Nephrology, Harry S Truman VA Medical Center
Georges Saab
University of Missouri-Columbia School of Medicine, Departments of Medicine, Physiology, and Pharmacology, Divisions of Endocrinology and Nephrology, Harry S Truman VA Medical Center
James R. Sowers
University of Missouri-Columbia School of Medicine, Departments of Medicine, Physiology, and Pharmacology, Divisions of Endocrinology and Nephrology, Harry S Truman VA Medical Center
The metabolic syndrome, also known as the cardiometabolic syndrome (CMS), is a state of metabolic and vascular dysregulation that is associated with activation of the renin-angiotensin-aldosterone system (RAAS). Clinical components of the CMS include central or visceral obesity, hypertension (HTN), dyslipidemia, insulin resistance/hyperinsulinemia, and microalbuminuria that collectively convey increases in oxidative stress, inflammation, and subsequent endothelial dysfunction. The cardio-renal inflammation and oxidative stress enhanced in the CMS increases the risk for cardiovascular disease (CVD) and renal disease end-points such as stroke, congestive heart failure, and chronic kidney disease (CKD). The development of proteinuria is known to herald progressive kidney disease (e.g. CKD) and both are now well accepted as CVD risk factors. Evidence suggests a role for visceral obesity, insulin resistance/hyperinsulinemia, HTN, and other components of the CMS lead to an increased risk for proteinuria and progressive loss of renal function. Intervention with agents that block the RAAS (e.g. ACE inhibitors and Angiotensin type 1 receptor blockers) have been shown to reduce proteinuria, CKD progression, and CVD events. Herein, we will examine the relationship between RAAS intervention and reductions in CKD and CVD events.
Key Words: cardiometabolic syndrome chronic kidney disease cardiovascular disease microalbuminuria.
References
- Alexander, C.M. et al. [2003] NCEP-defined metabolic syndrome, diabetes, and prevalence
- of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 52(5): 1210—1214.
- Aha [2004] American Heart Association. Heart Disease and Stroke Statistics — 2005 Update. Dallas, Tex: American Heart Association.
- Anderson, E.A. et al. [1991] Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest 87: 2246—2252.[Medline]
[Order article via Infotrieve]
- Assmann, G. and Schulte, H. [1988] The Prospective Cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease.
- Am Heart J 116: 1713—1724.
- Basu, S. et al. [1994] Lipomatous hypertrophy of the interatrial septum. Cardiovasc Surg 2: 229—231.[Medline]
[Order article via Infotrieve]
- Berne, C. et al. [1992] The sympathetic response to euglycaemic hyperinsulinaemia. Evidence from microelectrode nerve recordings in healthy subjects. Diabetologia 35: 873—879.[CrossRef][Medline]
[Order article via Infotrieve]
- Bharati, S. and Lev, M. [1995] Cardiac conduction system involvement in sudden death of obese young people. Am Heart J 129: 273—281.[CrossRef][Medline]
[Order article via Infotrieve]
- Bjorntorp, P. and Rosmond, R. [2000] Neuroendocrine abnormalities in visceral obesity. Int J Obes Relat Metab Disord 24(Suppl 2): S80—85.[CrossRef]
- Brenner, B.M. et al. [2001] Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345: 861—869.[Abstract/Free Full Text]
- Castro, J.P. et al. [2003] Cardiometabolic syndrome: pathophysiology and treatment. Curr Hypertens Rep 5: 393—401.[Medline]
[Order article via Infotrieve]
- Ceconi, C. et al. [2007] ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT. Cardiovasc Res 73(1): 237—246.[Abstract/Free Full Text]
- Chen, J. et al. [2003] Insulin resistance and risk for chronic kidney disease in nondiabetice US adults. J Am Soc Nephrol 14: 469—477.[Abstract/Free Full Text]
- Chen, J. et al. [2004] The Metabolic Syndrome and Chronic Kidney Disease in US Adults. Annals of Internal Medicine 140(3): 167—175.[Abstract/Free Full Text]
- DeFronzo, R.A. [1981] The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21: 165—171.[Medline]
[Order article via Infotrieve]
- DeFronzo, R.A. et al. [1975] The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 55: 845—855.[Medline]
[Order article via Infotrieve]
- DeFronzo, R.A. and Ferrannini, E. [1991] Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 173—194.[Abstract]
- Duflou, J. et al. [1995] Sudden death as a result of heart disease in morbid obesity. Am Heart J 130: 306—313.[CrossRef][Medline]
[Order article via Infotrieve]
- El-Atat, F.A. et al. [2004] Diabetes, Hypertension and cardiovascular derangements: Update on the pathophysiology and management. Curr Hypertens Rep 6: 215—223.[Medline]
[Order article via Infotrieve]
- El-Atat, F.A. et al. [2004] The relationship between hyperinsulinemia, hypertension and progressive renal disease. J Am Soc Nephrol 15(11): 2816—2827.[Abstract/Free Full Text]
- Engeli, S. and Sharma, A.M. [2001] The renin-angiotensin system and natriuretic peptides in obesity-associated hypertension. J Mol Med 79: 21—29.[CrossRef][Medline]
[Order article via Infotrieve]
- Engeli, S. and Sharma, A.M. [2002] Emerging concepts in the pathophysiology and treatment of obesity-associated hypertension. Curr Opin Cardiol 17: 355—359.[CrossRef][Medline]
[Order article via Infotrieve]
- Fox, K.M. [2003] EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 362: 782—788.[CrossRef][Medline]
[Order article via Infotrieve]
- Frohlich, E.D. et al. [1983] The problem of obesity and hypertension. Hypertension 5: I1171—78.
- Gerstein, H.C. et al. [2001] Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286(4): 421—426.[Abstract/Free Full Text]
- Gerstein, H.C. et al. [2000] Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 355: 253—259.[CrossRef][Medline]
[Order article via Infotrieve]
- Goodfriend, T.L. et al. [1998] Aldosterone in obesity. Endocr Res 24: 789—796.[Medline]
[Order article via Infotrieve]
- Goodfriend, T.L. et al. [1999] Plasma aldosterone, plasma lipoproteins, obesity and insulin resistance in humans. Prostaglandins Leukot Essent Fatty Acids 60: 401—405.[CrossRef][Medline]
[Order article via Infotrieve]
- Govindarajan, G. et al. Obesity and Hypertension: A Clinical Update. In eds, Ray R, Schiffrin E, and Sowers JR. [2006] Molecular Mechanisms in Hypertension. Taylor and Francis Pub, London, 397—406.
- Granger, J.P. et al. [1994] Abnormal pressure natriuresis in the dog model of obesity-induced hypertension. Hypertension 23: 18—11.[Abstract/Free Full Text]
- Hall, J.E. [1997] Mechanisms of abnormal renal sodium handling in obesity hypertension. Am J Hypertens 10: 49S—55S.[Medline]
[Order article via Infotrieve]
- Hall, J.E. et al. [1993] Obesity-induced hypertension. Renal function and systemic hemodynamics. Hypertension 22: 292—299.[Abstract/Free Full Text]
- Henegar, J.R. et al. [2001] Functional and structural changes in the kidney in the early stages of obesity. J Am Soc Nephrol 12: 1211—1217.[Abstract/Free Full Text]
- Hillege, H.L. et al. [2002] Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106: 1777.[Abstract/Free Full Text]
- Hoehner, C.M. et al. [2002] Association of the insulin resistance syndrome and microalbuminuria among non-diabetic native Americans. The Inter-Tribal HeartProject. J Am Soc Nephrol 13: 1626—1634.[Abstract/Free Full Text]
- Hsu, C.-Y. [2002] Does non-malignant hypertension cause renal insufficiency? Evidence-based perspective. Curr Opin Nephrol Hypertension 11: 267—272.[CrossRef][Medline]
[Order article via Infotrieve]
- Hunt, K.J. et al. [2004] National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 110(10): 1251—1257.[Abstract/Free Full Text]
- Isomaa, B. et al. [2001] Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24(4): 683—689.[Abstract/Free Full Text]
- Jacobs, D.B. et al. [1993] Effects of weight reduction on cellular cation metabolism and vascular resistance. Hypertension 21: 308—314.[Abstract/Free Full Text]
- Kambham, N. et al. [2001] Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 59: 1498—509.[CrossRef][Medline]
[Order article via Infotrieve]
- K/DOQI Clinical Practive Guidelines for chronic kidney disease: evaluation, classification, and stratification. [2002] Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 39: S1—246.[CrossRef][Medline]
[Order article via Infotrieve]
- Kenchaiah, S. et al. [2002] Obesity and the risk of heart failure. N Engl J Med 347: 305—313.[Abstract/Free Full Text]
- Kincaid-Smith, P. [2004] Hypothesis: obesity and the insulin resistance syndorme play a major role in end-stage renal failure attibuted to hypertension and labell "hypertensive nephrosclerosis". J Hypertension 22: 1051—1055.[CrossRef][Medline]
[Order article via Infotrieve]
- Klausen, K. et al. [2004] Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 110: 32.[Abstract/Free Full Text]
- Kurella, M. et al. [2005] Metabolic syndrome and the risk for chornic kidney disease among nondiabetic adults. The J Am Soc Nephrol 16: 2134—2140.[CrossRef]
- Kuusisto, J. et al. [1995] Hyperinsulinemic microalbuminuria: a new risk indicator for coronary heart disease. Circulation 90: 831.
- Lakka, H.M. et al. [2002] The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288(21): 2709—2716.[Abstract/Free Full Text]
- Lewis, E.J. et al. [2001] Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345(12): 851—860.[Abstract/Free Full Text]
- Licata, G. et al. [1990] Hypertension in obese subjects: distinct hypertensive subgroup. J Hum Hypertens 4: 37—41.[Medline]
[Order article via Infotrieve]
- Lip, G.Y. et al. [1994] Hypertension and the heart. Br Med Bull 50: 299—321.[Abstract/Free Full Text]
- Malik, S. et al. [2004] Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 110(10): 1245—1250.[Abstract/Free Full Text]
- Mangrum, A. and Bakris, G.L. [1997] Predictors of renal and cardiovascular mortality in patients with non-insulin-dependent diabetes: a brief overview of microalbuminuria and insulin resistance. J Diabetes Complications 11: 352—357.[CrossRef][Medline]
[Order article via Infotrieve]
- Massiera, F. et al. [2001] Angiotensinogen-deficient mice exhibit impairment of diet-induced weight gain with alteration in adipose tissue development and increased locomotor activity. Endocrinology 142: 5220—5225.[Abstract/Free Full Text]
- McFarlane, S.I. et al. [2001] Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab 86(2): 713—718.[Free Full Text]
- Meigs, J.B. et al. [2001] Framingham Offspring Study: Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care 24: 1403—1410.[Abstract/Free Full Text]
- Messerli, F.H. et al. [1981] Obesity and essential hypertension. Hemodynamics, intravascular volume, sodium excretion, and plasma renin activity. Arch Intern Med 141: 81—85.[Abstract]
- Messerli, F.H. et al. [1983] Dimorphic cardiac adaptation to obesity and arterial hypertension. Ann Intern Med 99: 757—761.[Medline]
[Order article via Infotrieve]
- Modan, M. and Halkin, H. [1991] Hyperinsulinemia or increased sympathetic drive as links for obesity and hypertension. Diabetes Care 14: 470—487.[Abstract]
- Mykkanen, L. et al. [1998] Microalbuminuria is associated with insulin resistance in nondiabetic subjects: The insulin resistance atherosclerosis study. Diabetes 47: 793—800.[Abstract]
- Pahor, M. et al. [2000] Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes. Diabetes Care 23: 888—892.[Abstract]
- Palaniappan, L. et al. [2003] Association between microalbuminuria and the metabolic syndrome: NHANES III. Am J Hypertens 16: 952—958.[CrossRef][Medline]
[Order article via Infotrieve]
- Parving, H.H. et al. [2001] Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345(12): 870—878.[Abstract/Free Full Text]
- Pereira, B.J. et al. [1994] Plasma levels of Il-1 beta, TNF alpha and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients. Kidney Int 45: 890—896.[Medline]
[Order article via Infotrieve]
- Rocchini, A.P. et al. [1997] Time course of insulin resistance associated with feeding dogs a high-fat diet. Am J Physiol 272: E147—154.[Medline]
[Order article via Infotrieve]
- Rocchini, A.P. et al. [1992] Forearm resistance vessel abnormalities and insulin resistance in obese adolescents. Hypertension 19: 615—620.[Abstract/Free Full Text]
- Rocchini, A.P. et al. [1990] Hyperinsulinemia and the aldosterone and pressor responses to angiotensin II. Hypertension 15: 861—866.[Abstract/Free Full Text]
- Rockstroh, J.K. et al. [1992] Stress response pattern in obesity and systemic hypertension. Am J Cardiol 70: 1035—1039.[CrossRef][Medline]
[Order article via Infotrieve]
- Roest, M. et al. [2001] Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women. Circulation 103: 3057.[Abstract/Free Full Text]
- Rowe, J.W. et al. [1981] Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 30: 219—225.[Medline]
[Order article via Infotrieve]
- Schmieder, R.E. and Messerli, F.H. [1993] Does obesity influence early target organ damage in hypertensive patients? Circulation 87: 1482—1488.[Abstract/Free Full Text]
- Schorr, U. et al. [1998] Relationship between angiotensinogen, leptin and blood pressure levels in young normotensive men. J Hypertens 16: 1475—1480.[CrossRef][Medline]
[Order article via Infotrieve]
- Shinohora, K. et al. [2002] Insulin Resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J Am Soc Nephrol 13: 1894—1900.[Abstract/Free Full Text]
- Sowers, J.R. [1998] Obesity and cardiovascular disease. Clin Chem 44: 1821—1825.[Abstract/Free Full Text]
- Sowers, J.R. [2004] Insulin resistance and hypertension. Am J Physiol Heart Circ Physiol 286: H1597—H1602.[Abstract/Free Full Text]
- Sowers, J.R. et al. [2001] Diabetes, hypertension, and cardiovascular disease: An update. Hypertension 37: 1053—1059.[Abstract/Free Full Text]
- Sowers, J.R. and Stump, C.S. [2004] Insights into the biology of diabetic vascular disease: what's new? Am J Hypertens 17(11Pt2): 2S—6S.[Medline]
[Order article via Infotrieve]
- Wachtell, K. et al. [2003] Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study. Ann Intern Med 139: 901.[Abstract/Free Full Text]
- Weir, M.R. et al. [1998] Nocturnal reduction of blood pressure and the antihypertensive response to a diuretic or angiotensin converting enzyme inhibitor in obese hypertensive patients. TROPHY Study Group. Am J Hypertens 11: 914—920.[CrossRef][Medline]
[Order article via Infotrieve]

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
|