Background: It is being increasingly recognized that compared to BP recordings in the clinic, BP recordings outside the clinic are stronger predictors of poor cardiorenal outcomes. When BP is recorded both in the clinic and outside, hypertension can be categorized depending on the location of BP recording. These categories include white coat hypertension, sustained normotension (NTN), sustained hypertension (HTN), and masked hypertension (MHTN). MHTN is defined as normal BP in the clinic but elevated BP outside the clinic. Our meta-analysis revealed that 40% of CKD patients thought to be normotensive in fact had MHTN. The largest CKD cohort studied to date included a cross-sectional analysis of 209 patients (enabled through this period of VAMR funding) who were selected because they had normal BP (<140/90 mmHg) in the clinic. We found that the prevalence of MHTN was ~40%. For the first time we demonstrated that the diagnosis of MHTN was reproducible. This has not been reported in the past even among patients without CKD. Moreover, MHTN in our cohort was associated with greater left ventricular mass index, increased arterial stiffness, greater albuminuria, and nocturnal natriuresis. Long-term goal: The overall goal of this study in Veterans with CKD is to investigate target organ damage, prognosis, and mechanisms of "masked hypertension ", defined by an average awake ambulatory pressure of 125/75 mm Hg or more and clinic BP below 130/80 mm Hg. Hypothesis: We hypothesize that NTN, MHTN and HTN is a continuum. We hypothesize that a graded relationship among NTN, MHTN and HTN will exist such that with a worse hypertension category will: 1) have greater worsening of hypertension and therefore greater end-organ damage;2) will experience greater all-cause mortality and cardiovascular and renal morbidity;3) have associations with greater target organ damage and mortality the magnitude of which will depend on how MHTN is defined;and 4) experience greater sleep disturbances, reduced day-time physical activity, increased body fat, and greater exercise-induced increased BP. Also, dietary Na intake will modulate subsequent increase in ambulatory BP and other adverse outcomes. Goals: This proposed study will enable us to determine (1) the incidence of worsening of hypertension and the occurrence of target organ damage among NTN, MHTN, and HTN, (2) Compare the incidence of cardiorenal events (hospitalized heart failure, MI, stroke, ESRD, kidney transplantation, death) among the hypertension categories (3) Compare the prognostic value of two definitions of MHTN (a CKD-specific definition, noted above and the conventional definition of MHTN) and (4) examine the mechanistic relationship of MHTN with sleep disturbances, reduced day-time activity, increasing adiposity and increments in ambulatory BP with greater sodium intake. Methods: This project will study 450 subjects with CKD with NTN, MHTN, and HTN. Participants will have their clinic BP measured on three occasions, ambulatory BP once, and home BP twice over a one month period. Target organ damage will be assessed using LV mass and pulse wave velocity by echocardiogram and 24 hour urine for albuminuria. Examinations will be repeated biannually. Sleep will be measured using portable multichannel overnight sleep monitoring. Body composition will be measured by the gold-standard measurement of air-displacement plethysmography (Bod Pod). Activity will be measured by 7-day wrist accelerometer. Greater pressor effect with physical activity will be measured on a bicycle ergometer. We will follow for ESRD and cardiovascular events. Novelty: This proposal will provide new insights on the prognostic implications and mechanisms of masked hypertension in patients with CKD. Relevance to VA: To the extent that this study increases our understanding of the differences between clinic and out of clinic BP monitoring, it will help to explain why the latter is a better indicator of prognosis. The evaluation of target organ damage, ESRD, and cardiovascular events among those with masked hypertension may unmask its malignant characteristics and improve our ability to treat this condition more effectively.

Public Health Relevance

Masked hypertension (MHTN) is defined as normal BP in the clinic but elevated BP outside the clinic. In a cross- sectional study of >200 Veterans with CKD we have found a high prevalence of MHTN (~40%). We have found that MHTN in CKD is associated with greater left ventricular mass index, increased arterial stiffness, greater albuminuria, and nocturnal natriuresis. We now propose to longitudinally investigate, among Veterans with CKD, target organ damage, prognosis, and mechanisms of MHTN. We hypothesize that normotension, MHTN and hypertension is a continuum such that a worse hypertension category will have greater end-organ damage;will experience greater all-cause mortality and cardiovascular and renal morbidity;and experience greater sleep disturbances, reduced day-time physical activity, increased body fat, and greater exercise-induced increased BP. Also, dietary Na intake will modulate subsequent increase in ambulatory BP and other adverse outcomes. The evaluation of target organ damage and hard outcomes among those with MHTN may unmask its malignant characteristics and improve our ability to treat this condition more effectively.

Agency
National Institute of Health (NIH)
Type
Non-HHS Research Projects (I01)
Project #
5I01CX000829-02
Application #
8659974
Study Section
Nephrology (NEPH)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Rlr VA Medical Center
Department
Type
DUNS #
City
Indianapolis
State
IN
Country
United States
Zip Code
46202