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Published in: Cardiovascular Drugs and Therapy 4/2009

01-08-2009

Cardiovascular and Renal Surrogate Markers in the Clinical Management of Hypertension

Author: Alan S. Maisel

Published in: Cardiovascular Drugs and Therapy | Issue 4/2009

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Abstract

Introduction

Surrogate markers represent a significant contribution to early diagnosis, longitudinal prognoses, and outcome prediction in cases of hypertension. They often enable detection of disease and disease potential when the disease is still subclinical and are useful noninvasive tools for designing and evaluating therapeutic programs. Surrogate markers are increasingly employed as predictive endpoints for treatment.

Methods

Key studies supporting the importance of surrogate markers as diagnostic and prognostic predictors of cardiovascular and renal clinical outcomes in hypertension, as well as what is known about the effects of renin-angiotensin-aldosterone system-blocking agents on these biomarkers were reviewed.

Results

Clinical data supporting the use of surrogate markers for heart failure, such as brain natriuretic peptide (BNP) and N-terminal prohormone BNP; markers for renal function, such as urinary albumin to creatinine ratio (UACR), urinary albumin excretion rates (UAER), and creatinine, reflecting glomerular filtration; and markers of cardiac remodeling, such as left ventricular hypertrophy and calculations of left ventricular mass index (LVMI), were reviewed for their utility in improving prognosis and treatment efficacy. Finally, hypertension treatment with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and potentially direct renin inhibitors can significantly improve outcomes predicted by surrogate markers.

Conclusions

BNP, UACR, UAER, and LVMI, among others, have been increasingly established as valid surrogate markers with significant value for hypertension prognosis and therapy. The benefits of using surrogate markers to gauge the effectiveness of hypertension therapy in reducing renal and cardiac complications can be seen in improved morbidity and mortality.
Literature
6.
go back to reference Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med. 1996;125:605–13.PubMed Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med. 1996;125:605–13.PubMed
9.
go back to reference Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–26. doi:10.1161/CIRCULATIONAHA.108.189141.PubMedCrossRef Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–26. doi:10.​1161/​CIRCULATIONAHA.​108.​189141.PubMedCrossRef
11.
go back to reference Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114:345–52.PubMed Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114:345–52.PubMed
13.
go back to reference Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13. doi:10.1016/S0140-6736(02)11911-8.PubMedCrossRef Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13. doi:10.​1016/​S0140-6736(02)11911-8.PubMedCrossRef
15.
go back to reference Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet. 1990;335:827–38. doi:10.1016/0140-6736(90)90944-Z.PubMedCrossRef Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet. 1990;335:827–38. doi:10.​1016/​0140-6736(90)90944-Z.PubMedCrossRef
16.
go back to reference MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335:765–74. doi:10.1016/0140-6736(90)90878-9.PubMedCrossRef MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335:765–74. doi:10.​1016/​0140-6736(90)90878-9.PubMedCrossRef
18.
go back to reference Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006;144:21–8.PubMed Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006;144:21–8.PubMed
19.
go back to reference McCullough PA, Li S, Jurkovitz CT, et al. CKD and cardiovascular disease in screened high-risk volunteer and general populations: the Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999–2004. Am J Kidney Dis. 2008;51:S38–45. doi:10.1053/j.ajkd.2007.12.017.PubMedCrossRef McCullough PA, Li S, Jurkovitz CT, et al. CKD and cardiovascular disease in screened high-risk volunteer and general populations: the Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999–2004. Am J Kidney Dis. 2008;51:S38–45. doi:10.​1053/​j.​ajkd.​2007.​12.​017.PubMedCrossRef
21.
go back to reference Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36:646–61.PubMed Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36:646–61.PubMed
23.
go back to reference Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007;13:9–20.PubMed Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007;13:9–20.PubMed
25.
go back to reference Bhatia V, Nayyar P, Dhindsa S. Brain natriuretic peptide in diagnosis and treatment of heart failure. J Postgrad Med. 2003;49:182–5.PubMed Bhatia V, Nayyar P, Dhindsa S. Brain natriuretic peptide in diagnosis and treatment of heart failure. J Postgrad Med. 2003;49:182–5.PubMed
30.
go back to reference Latini R, Masson S, Wong M, et al. Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med. 2006;119:e23–30.PubMedCrossRef Latini R, Masson S, Wong M, et al. Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med. 2006;119:e23–30.PubMedCrossRef
37.
go back to reference Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:995–1003. doi:10.1016/S0140-6736(02)08089-3.PubMedCrossRef Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:995–1003. doi:10.​1016/​S0140-6736(02)08089-3.PubMedCrossRef
38.
41.
go back to reference McMurray JJV, Pitt B, Latini R, et al. Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circ Heart Fail. 2008;1:17–24.CrossRefPubMed McMurray JJV, Pitt B, Latini R, et al. Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circ Heart Fail. 2008;1:17–24.CrossRefPubMed
42.
go back to reference Recio-Mayoral A, Kaski JC, McMurray JJ, et al. Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY. Cardiovasc Drugs Ther. 2007;21:459–65. doi:10.1007/s10557-007-6069-4.PubMedCrossRef Recio-Mayoral A, Kaski JC, McMurray JJ, et al. Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY. Cardiovasc Drugs Ther. 2007;21:459–65. doi:10.​1007/​s10557-007-6069-4.PubMedCrossRef
44.
go back to reference Schillaci G, Verdecchia P, Porcellati C, et al. Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension. Hypertension. 2000;35:580–6.PubMed Schillaci G, Verdecchia P, Porcellati C, et al. Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension. Hypertension. 2000;35:580–6.PubMed
45.
go back to reference Hammond IW, Devereux RB, Alderman MH, et al. The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed patients with uncomplicated hypertension. J Am Coll Cardiol. 1986;7:639–50.PubMedCrossRef Hammond IW, Devereux RB, Alderman MH, et al. The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed patients with uncomplicated hypertension. J Am Coll Cardiol. 1986;7:639–50.PubMedCrossRef
46.
go back to reference Liebson PR, Grandits G, Prineas R, et al. Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study (TOMHS). Circulation. 1993;87:476–86.PubMed Liebson PR, Grandits G, Prineas R, et al. Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study (TOMHS). Circulation. 1993;87:476–86.PubMed
48.
50.
go back to reference Gardin JM, McClelland R, Kitzman D, et al. M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). Am J Cardiol. 2001;87:1051–7. doi:10.1016/S0002-9149(01)01460-6.PubMedCrossRef Gardin JM, McClelland R, Kitzman D, et al. M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). Am J Cardiol. 2001;87:1051–7. doi:10.​1016/​S0002-9149(01)01460-6.PubMedCrossRef
52.
go back to reference Levy D, Salomon M, D’Agostino RB, Belanger AJ, Kannel WB. Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy. Circulation. 1994;90:1786–93.PubMed Levy D, Salomon M, D’Agostino RB, Belanger AJ, Kannel WB. Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy. Circulation. 1994;90:1786–93.PubMed
53.
54.
go back to reference Rosenberg M, Zugck C, Nelles M, et al. Osteopontin, a new prognostic biomarker in patients with chronic heart failure. Circ Heart Fail. 2008;1:43–9.CrossRefPubMed Rosenberg M, Zugck C, Nelles M, et al. Osteopontin, a new prognostic biomarker in patients with chronic heart failure. Circ Heart Fail. 2008;1:43–9.CrossRefPubMed
58.
go back to reference Devereux RB, Palmieri V, Sharpe N, et al. Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial. Circulation. 2001;104:1248–54. doi:10.1161/hc3601.095927.PubMedCrossRef Devereux RB, Palmieri V, Sharpe N, et al. Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial. Circulation. 2001;104:1248–54. doi:10.​1161/​hc3601.​095927.PubMedCrossRef
60.
go back to reference Dahlof B, Gosse P, Gueret P, et al. Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study. J Hypertens. 2005;23:2063–70.PubMed Dahlof B, Gosse P, Gueret P, et al. Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study. J Hypertens. 2005;23:2063–70.PubMed
61.
go back to reference Solomon S, Appelbaum E, Manning W, et al. Effect of the direct renin inhibitor aliskiren either alone or in combination with losartan, compared to losartan, on left ventricular mass in patients with hypertension and left ventricular hypertrophy (ALLAY) trial [late breaker presentation]. Presented at: American College of Cardiology Scientific Sessions; March 29–April 1, 2008; Chicago, IL. Solomon S, Appelbaum E, Manning W, et al. Effect of the direct renin inhibitor aliskiren either alone or in combination with losartan, compared to losartan, on left ventricular mass in patients with hypertension and left ventricular hypertrophy (ALLAY) trial [late breaker presentation]. Presented at: American College of Cardiology Scientific Sessions; March 29–April 1, 2008; Chicago, IL.
62.
go back to reference K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1–266. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1–266.
63.
64.
65.
66.
71.
go back to reference Malyszko J, Bachorzewska-Gajewska H, Malyszko JS, Pawlak K, Dobrzycki S. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in hypertensive and normotensive patients with coronary artery disease. Nephrol Carlton. 2008;13:153–6. doi:10.1111/j.1440-1797.2007.00899.x.CrossRef Malyszko J, Bachorzewska-Gajewska H, Malyszko JS, Pawlak K, Dobrzycki S. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in hypertensive and normotensive patients with coronary artery disease. Nephrol Carlton. 2008;13:153–6. doi:10.​1111/​j.​1440-1797.​2007.​00899.​x.CrossRef
72.
go back to reference Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321:1440–4. doi:10.1136/bmj.321.7274.1440.PubMedCrossRef Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321:1440–4. doi:10.​1136/​bmj.​321.​7274.​1440.PubMedCrossRef
73.
Metadata
Title
Cardiovascular and Renal Surrogate Markers in the Clinical Management of Hypertension
Author
Alan S. Maisel
Publication date
01-08-2009
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 4/2009
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-009-6177-4

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