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Prehypertension: Is It Relevant for Nephrologists?

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Prehypertension: Is It Relevant for Nephrologists? Special Feature Prehypertension: Is It Relevant for Nephrologists? Norman M. Kaplan Department of Internal Medicine, Division of Hypertension, University of Texas Southwestern Medical School, Dallas, Texas Prehypertension has been proposed as the diagnosis for the presence of blood pressures >120/80 mmHg but <140/90 mmHg. It covers more than 60 million people in the United States and nephrologists will increasingly be involved with them. This review describes its relevance to nephrologists. Clin J Am Soc Nephrol 4: 1381–1383, 2009. doi: 10.2215/CJN.02340409 ephrologists will rarely deal with patients who have experienced a two-fold increase in death from cardiovascular prehypertension (i.e., BP below hypertension [140/90 diseases. mmHg] but above ideal [120/80 mmHg]), which In addition to these mortality data, a number of studies of NϾ includes 60 million people in the United States (1). Because smaller populations have shown an increase in nonfatal target there are hardly enough nephrologists to care for the increasing organ damage (3). For the sake of brevity, emphasis is placed number of patients with chronic kidney disease, why should on those that relate to the kidneys: they be concerned about patients who do not yet have hyper- • Left ventricular hypertrophy (4) tension? • Coronary calcification (5) The reasons include the following: First, multiple data show • Reduced coronary flow reserve (6) that people with prehypertension often have subclinical target • Progression of coronary atherosclerosis (7) organ damage, including nephropathy. Second, the families of • Increases in ischemic coronary disease and stroke (8) patients with chronic kidney disease (CKD) harbor an in- • Poor cognitive function (9) creased prevalence of nephropathy, and they need early recog- • Retinal vascular changes (10) nition. Third, if recognized, then it may be possible to reverse • Elevated serum uric acid (11) the usual progression into overt hypertension and thereby pre- vent patients from developing hypertension-related organ Albuminuria in levels even below the level that defines mi- damage. croalbuminuria is predictive of both hypertension (12) and cardiovascular morbidity and mortality, independent of renal Evidence of Subclinical Target Organ function, hypertension, or diabetes (13). Patients with prehy- Damage pertension have an increased prevalence of microalbuminuria During the past 10 yrs, a large body of evidence has shown (14). In this study of almost 2700 patients, those with prehy- the risks of prehypertensive levels of BP. Perhaps the most pertension had a prevalence of microalbuminuria of 4.9%, com- convincing are the data from the Prospective Studies Collabo- pared with a prevalence of 2.8% in those with normal BP. ration, which followed almost 1 million people with no previ- Similar associations have been reported from other populations ous vascular disease prospectively for a total of 12.7 million (15). Of additional interest, serum uric acid, believed by some to person-years in 61 observational studies (2) and examined the be a major determinant of hypertension and atherosclerosis, is relationship between levels of BP and subsequent mortality. associated with microalbuminuria in individuals with prehy- The data show a continuous increase in mortality from both pertension (16). stroke and ischemic heart disease from 115/75 mmHg, the lowest level with a large enough group that could be followed. Predictors of Prehypertension In those with a 20-mmHg higher systolic BP or a 10-mmHg Because prehypertension is one step toward hypertension, higher diastolic BP, mortality rates doubled; therefore, patients the same factors are involved in the development of both. with BP of 135/85, well within the range of prehypertension, Obesity is foremost, with male gender and black race also involved (17). In addition, these factors are associated with more prehypertension: Diabetes, impaired glucose tolerance, Received April 8, 2009. Accepted May 26, 2009. the metabolic syndrome, dyslipidemia, and smoking (18). Perhaps the main reason that nephrologists should consider Published online ahead of print. Publication date available at www.cjasn.org. prehypertension is their opportunity to identify many of those Correspondence: Dr. Norman M. Kaplan, Department of Internal Medicine, who are most likely to develop it: The families of their patients Division of Hypertension, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390-8586. Phone: 214-648-2103; Fax: 214- with CKD or ESRD. As shown in the Kidney Evaluation and 648-3063; E-mail: [email protected] Awareness Program in Sheffield (KEAPS) trial, relatives of Copyright © 2009 by the American Society of Nephrology ISSN: 1555-9041/408–1381 1382 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 4: 1381–1383, 2009 patients with CKD were six times more likely to have mi- 9. Knecht S, Wersching H, Lohmann H, Bruchmann M, Dun- croalbuminuria than nonrelatives (19). With the association of ing T, Dziewas R, Berger K, Ringelstein EB: High-normal prehypertension with microalbuminuria, it is likely that many blood pressure is associated with poor cognitive perfor- individuals with prehypertension would be identified with mance. Hypertension 51: 663–668, 2008 screening. That a relative has CKD should motivate those iden- 10. Nguyen TT, Wang JJ, Wong TY: Retinal vascular changes in pre-diabetes and prehypertension: New findings and tified to change lifestyle or take medication to prevent devel- their research and clinical implications. Diabetes Care 30: oping CKD. 2708–2715, 2007 11. Syamala S, Li J, Shankar A: Association between serum Value of Therapy uric acid and prehypertension among US adults. J Hyper- Both lifestyle changes (20) and drug therapy (21–23) have tens 25: 1583–1589, 2007 been shown at least temporarily to slow the progression of 12. Forman JP, Fisher ND, Schopick EL, Curhan GC: Higher prehypertension into hypertension. The trials, up until now, levels of albuminuria within the normal range predict in- have likely been too late to stop the progress, because, at least cident hypertension. J Am Soc Nephrol 19: 1983–1988, 2008 in the spontaneously hypertensive rat (24), antihypertensive 13. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, therapy must be given much earlier in the lifespan to prevent Clausen P, Scharling H, Appleyard M, Jensen JS: Very low the future development of hypertension. levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 110: Conclusions 32–35, 2004 Nephrologists have the closest relationship to hypertension 14. Kim BJ, Lee HJ, Sung KC, Kim BS, Kang JH, Lee MH, Park JR: than any other specialists. To be even more effective in the early Comparison of microalbuminuria in 2 blood pressure catego- recognition and, hopefully, the prevention of overt hyperten- ries of prehypertensive subjects. Circ J 71: 1283–1287, 2007 sion, they need to keep prehypertension in mind. 15. Hsu CC, Brancati FL, Astor BC, Kao WH, Steffes MW, Folsom AR, Coresh J: Blood pressure, atherosclerosis, and Disclosures albuminuria in 10,113 participants in the atherosclerosis None. risk in communities study. J Hypertens 27: 397–409, 2009 16. Lee JE, Kim YG, Choi YH, Huh W, Kim DJ, Oh HY: Serum uric acid is associated with microalbuminuria in prehyper- References tension. Hypertension 47: 962–967, 2006 1. Elliott WJ, Black HR: Prehypertension. Nat Clin Pract Car- 17. Toprak A, Wang H, Chen W, Paul T, Ruan L, Srinivasan S, diovasc Med 4: 538–548, 2007 Berenson G: Prehypertension and black-white contrasts in 2. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, cardiovascular risk in young adults: Bogalusa Heart Study. Prospective Studies Collaboration: Age-specific relevance J Hypertens 27: 243–250, 2009 of usual blood pressure to vascular mortality: A meta- 18. Bo S, Gambino R, Gentile L, Pagano G, Rosato R, Saracco analysis of individual data for one million adults in 61 GM, Cassader M, Durazzo M, Cavallo-Perin P: High-nor- prospective studies [published erratum appears in Lancet mal blood pressure is associated with a cluster of cardio- 361: 1060, 2003]. Lancet 360: 1903–1913, 2002 vascular and metabolic risk factors: A population-based 3. Carrington M: Prehypertension causes a mounting prob- study. J Hypertens 27: 102–108, 2009 lem of harmful cardiovascular disease risk in young adults. 19. Bello AK, Peters J, Wight J, de Zeeuw D, El Nahas M, J Hypertens 27: 214–215, 2009 European Kidney Institute: A population-based screening 4. Kokkinos P, Pittaras A, Narayan P, Faselis C, Singh S, for microalbuminuria among relatives of CKD patients: Manolis A: Exercise capacity and blood pressure associa- The Kidney Evaluation and Awareness Program in Shef- tions with left ventricular mass in prehypertensive indi- field (KEAPS). Am J Kidney Dis 52: 434–443, 2008 viduals. Hypertension 49: 55–61, 2007 20. Bavikati VV, Sperling LS, Salmon RD, Faircloth GC, Gor- 5. Pletcher MJ, Bibbins-Domingo K, Lewis CE, Wei GS, Sid- don TL, Franklin BA, Gordon NF: Effect of comprehensive ney S, Carr JJ, Vittinghoff E, McCulloch CE, Hulley SB: therapeutic lifestyle changes on prehypertension. Am J Car- Prehypertension during young adulthood and coronary diol 102: 1677–1680, 2008 calcium later in life. Ann Intern Med 149: 91–99, 2008 21. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, 6. Erdogan D, Yildirim I,
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