Cardiovascular and Renal Surrogate Markers in the Clinical Management of Hypertension
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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.
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.
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.
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.
Key wordsSurrogate markers Hypertension Heart failure Kidney impairments Left ventricle enlargement Aliskiren
This review article was sponsored by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. Novartis contributed to the identification of subject matter expert to author this manuscript and was provided the opportunity to discuss included content and review data for factual correctness and consistency.
Dr. Maisel received a modest honorarium from Novartis and editorial assistance from Complete Healthcare Communications, Inc. (CHC).
The opinions expressed in the review article are those of the author and do not necessarily represent the views of the journal, author’s institutions, CHC, or Novartis, unless otherwise specified.
Disclosure of off-label use
This review article may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. Authors have been asked to disclose any off-label (unapproved) use of products mentioned in this article. If an off-label use is mentioned, each author is responsible for identifying the drug and its off-label indication. CHC, and Novartis do not recommend the use of any agent outside of the labeled indications. Please refer to the full prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Readers have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this article is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this article should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
- 1.Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89–95. doi: 10.1067/mcp.2001.113989.
- 9.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.PubMedCrossRefGoogle Scholar
- 16.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.PubMedCrossRefGoogle Scholar
- 19.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.PubMedCrossRefGoogle Scholar
- 42.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.PubMedCrossRefGoogle Scholar
- 47.Okin PM, Devereux RB, Jern S, et al. Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: The Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study. Circulation. 2003;108:684–90. doi: 10.1161/01.CIR.0000083724.28630.C3.PubMedCrossRefGoogle Scholar
- 50.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.PubMedCrossRefGoogle Scholar
- 58.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.PubMedCrossRefGoogle Scholar
- 59.Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation. 2003;108:1831–8. doi: 10.1161/01.CIR.0000091405.00772.6E.PubMedCrossRefGoogle Scholar
- 61.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.Google Scholar
- 62.K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1–266.Google Scholar
- 69.Ibsen H, Olsen MH, Wachtell K, et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study. Hypertension. 2005;45:198–202. doi: 10.1161/01.HYP.0000154082.72286.2a.PubMedCrossRefGoogle Scholar
- 71.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.CrossRefGoogle Scholar
- 72.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.PubMedCrossRefGoogle Scholar