Association between high-normal albuminuria and risk factors for cardiovascular and renal disease in essential hypertensive men.

BACKGROUND Microalbuminuria (overnight urinary albumin excretion [UAE] > 15 microg/min) is associated with cardiovascular risk factors and predicts morbid events in hypertensive subjects. However, albuminuria is not a dichotomous variable, and a relationship with cardiovascular risk factors may extend below that conventional threshold. METHODS We studied 186 never-treated, glucose-tolerant, normalbuminuric (overnight UAE < or = 15 microg/min), essential hypertensive men with normal renal function (serum creatinine < 1.4 mg/dL). Study variables were 24-hour ambulatory blood pressure (BP), cardiac structure and geometry (by echocardiography), body weight, fasting insulin levels, insulin sensitivity (the Homeostasis Model Assessment index), and creatinine clearance (from overnight collections or through the Cockcroft formula) analyzed as a function of ascending urine albumin quartiles (cutoff values, 4.3, 6.3, and 9.4 microg/min; n = 47, 45, 47, and 47, respectively). RESULTS As compared with the three bottom fourths, patients with high-normal albuminuria (albumin, 9.4 to 15 microg/min) had a greater 24-hour BP, greater relative wall thickness, more frequent concentric left ventricular hypertrophy, heavier body size, increased fasting insulin levels, reduced insulin sensitivity, and greater creatinine clearance. CONCLUSIONS High-normal albuminuria in uncomplicated essential hypertensive men is associated with an adverse cardiovascular and metabolic risk profile. Furthermore, hyperfiltration in the presence of minimally increased albuminuria may underlie an augmented glomerular blood flow and hydraulic pressure conducive to glomerular hypertension and, eventually, renal insufficiency. Overall, these data confirm the appropriateness to shift downward the limits for diagnosing microalbuminuria in essential hypertension, as indicated from previous prospective studies.

[1]  N. Christensen,et al.  Dual effect of insulin on plasma volume and transcapillary albumin transport , 1992, Diabetologia.

[2]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[3]  M. Mariani,et al.  Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension , 2002, Journal of Human Hypertension.

[4]  G. Dell'omo,et al.  Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular disease , 2001, Vascular medicine.

[5]  S. Yusuf,et al.  Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. , 2001, JAMA.

[6]  D. Grobbee,et al.  Excessive Urinary Albumin Levels Are Associated With Future Cardiovascular Mortality in Postmenopausal Women , 2001, Circulation.

[7]  K. Borch-Johnsen,et al.  Elevated Urinary Albumin Excretion Is Associated With Impaired Arterial Dilatory Capacity in Clinically Healthy Subjects , 2001, Circulation.

[8]  P. Okin,et al.  Prognostic implications of left ventricular hypertrophy. , 2001, American heart journal.

[9]  H. Hillege,et al.  Low Levels of Urinary Albumin Excretion Are Associated with Cardiovascular Risk Factors in the General Population , 2000, Clinical chemistry and laboratory medicine.

[10]  D. Zeeuw,et al.  Urinary albumin excretion is associated with renal functional abnormalities in a nondiabetic population. , 2000, Journal of the American Society of Nephrology : JASN.

[11]  F. Mee,et al.  Use and interpretation of ambulatory blood pressure monitoring: recommendations of the British Hypertension Society , 2000, BMJ : British Medical Journal.

[12]  M. Schroll,et al.  Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. , 2000, Hypertension.

[13]  P. Verdecchia,et al.  Prognostic value of ambulatory blood pressure : current evidence and clinical implications. , 2000, Hypertension.

[14]  D. Gaudet,et al.  Glomerular hyperfiltration in hypertensive African Americans. , 2000, Hypertension.

[15]  S. Yusuf,et al.  Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study. The HOPE Study Investigators. , 2000, Diabetes care.

[16]  G. Desideri,et al.  Early upregulation of endothelial adhesion molecules in obese hypertensive men. , 1999, Hypertension.

[17]  G. Leoncini,et al.  Left ventricular geometry and function in patients with essential hypertension and microalbuminuria. , 1999, Journal of hypertension.

[18]  M. Fujishima,et al.  Effect of hyperinsulinemia on renal function in a general Japanese population: the Hisayama study. , 1999, Kidney international.

[19]  F C Luft,et al.  Glomerular hyperfiltration during sympathetic nervous system activation in early essential hypertension. , 1997, Journal of the American Society of Nephrology : JASN.

[20]  E. Ferrannini,et al.  Effect of Insulin on Systemic and Renal Handling of Albumin in Nondiabetic and NIDDM Subjects , 1997, Diabetes.

[21]  G. Reboldi,et al.  Prognostic value of left ventricular mass and geometry in systemic hypertension with left ventricular hypertrophy. , 1996, The American journal of cardiology.

[22]  T. Ishimitsu,et al.  Relationship between left ventricular geometry and natriuretic peptide levels in essential hypertension. , 1996, Hypertension.

[23]  R. Bergman,et al.  Insulin Sensitivity and Atherosclerosis , 1996 .

[24]  B. Brenner,et al.  Brenner & Rector's the Kidney , 1996 .

[25]  S. Bianchi,et al.  Insulin resistance in microalbuminuric hypertension. Sites and mechanisms. , 1995, Hypertension.

[26]  J. Laragh,et al.  Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. , 1995, Journal of the American College of Cardiology.

[27]  B. Fagerberg,et al.  Microalbuminuria, insulin sensitivity and haemostatic factors in non‐diabetic treated hypertensive men , 1995, Journal of internal medicine.

[28]  B. Guy-grand,et al.  Microalbuminuria and body fat distribution in obese subjects. , 1994, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[29]  G. Dell'omo,et al.  Microalbuminuria and endothelial dysfunction in essential hypertension , 1994, The Lancet.

[30]  S. Bianchi,et al.  Elevated serum insulin levels in patients with essential hypertension and microalbuminuria. , 1994, Hypertension.

[31]  J. Laragh,et al.  Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension. , 1994, Journal of the American College of Cardiology.

[32]  J. Manson,et al.  Body weight and mortality. A 27-year follow-up of middle-aged men. , 1993, JAMA.

[33]  B. Brenner,et al.  Hemodynamic theory of progressive renal disease: a 10-year update in brief review. , 1993, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[34]  M. Koopman,et al.  Discrepancy between circadian rhythms of inulin and creatinine clearance. , 1992, The Journal of laboratory and clinical medicine.

[35]  J. Laragh,et al.  Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. , 1992, Journal of the American College of Cardiology.

[36]  J. Neaton,et al.  Blood Pressure (Systolic and Diastolic) and Risk of Fatal Coronary Heart Disease , 1989, Hypertension.

[37]  J. McMurray,et al.  The effect of atrial natriuretic factor on urinary albumin and beta 2-microglobulin excretion in man. , 1988, Journal of hypertension.

[38]  M. N. Levy,et al.  Cardiac responses to increased afterload. State-of-the-art review. , 1982 .

[39]  Cockcroft Dw,et al.  Prediction of Creatinine Clearance from Serum Creatinine , 1976 .