Nocturnal high blood pressure and left ventricular hypertrophy in patients with chronic kidney disease
- Giong Rieng District Medical Center, Kien Giang, Viet Nam
- University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam
- Nhan Dan Gia Dinh Hospital, Ho Chi Minh City, Viet Nam
Abstract
Background: Patients diagnosed with chronic kidney disease (CKD) have a heightened risk of developing masked uncontrolled hypertension (MUCH), leading to hypertension-induced organ damage. This study aimed to estimate the prevalence and characteristics of MUCH and to investigate risk factors of left ventricular hypertrophy (LVH) in those with CKD.
Methods: A retrospective study was conducted on data from 178 patients diagnosed with CKD and having controlled office blood pressure at Nhan Dan Gia Dinh Hospital between October 2018 and June 2019. These participants underwent 24-hour ambulatory blood pressure monitoring (ABPM) using the SunTech Oscar 2 device. Subsequently, echocardiography was performed to assess for the presence of LVH.
Results: The prevalence of MUCH was 48.9%. Notably, all patients with MUCH demonstrated elevated nighttime blood pressure. LVH was more prevalent in the MUCH group when compared to those with controlled hypertension (55.2% and 38.5%, respectively). MUCH and CKD staging 4-5 were independent risk factors of LVH with ORs 1.97 (95% CI, 1.03-3.85) and 2.58 (95% CI, 1.16-5.94), respectively.
Conclusions: We recommend routinely using ABPM to detect MUCH in CKD patients even with controlled office hypertension. Screening for LVH is necessary in those with MUCH.
Introduction
Ambulatory blood pressure monitoring (ABPM) provides valuable data on mean 24-hour, daytime, and nocturnal blood pressure (BP). Patients with masked uncontrolled hypertension (MUCH) exhibit controlled office BP but elevated out-of-office BP. Similar to sustained hypertension, MUCH increases the risk of cardiovascular events and mortality compared to controlled BP1, 2. Notably, MUCH in CKD patients contributes to the progression of left ventricular hypertrophy (LVH) and end-stage renal disease (ESRD), but there are few related studies on the Vietnamese CKD population3, 4, 5. Therefore, this study aimed to estimate the prevalence and characteristics of MUCH and to examine the risk factors associated with left ventricular hypertrophy (LVH) in individuals with chronic kidney disease (CKD).
Method
Study design and participants
We revisited data from 196 patients with CKD and controlled office BP undergoing 24-hour ABPM at Nhan Dan Gia Dinh Hospital from October 2018 to June 2019 with the following study criteria as follows:
We excluded 4 patients since they stopped engaging in the study and 14 patients who had inadequate ABPM recordings, thus yielding 178 subjects completing the investigation. The recruitment flow is illustrated in Figure 1.
Recruitment flow.
Abbreviations: CKD: chronic kidney disease, ABPM: ambulatory blood pressure monitoring
Data collection
Office BP readings were taken from the Yamasu sphygmomanometer, Japan, by trained nurses at clinics. Three sitting readings were recorded in a row, and office BP was calculated as the average of the last two measurements. Ambulatory blood pressure in 24 hours was measured by the American SunTech Oscar 2 device. The size of the cuff was selected according to the patient's arm circumference. AccuWinPro version 3.0 software was used to process the results. The daytime and nighttime measuring intervals were set to be every 30 minutes and 60 minutes, respectively. BP readings were not displayed on the meter screen. Patients with acceptable BP measurements greater than 70% of total measurements were considered to have adequate ABPM assessments. Controlled office BP was defined as having systolic BP < 140 mmHg and diastolic BP < 90 mmHg at clinics. We classified patients into 2 groups based on MUCH and controlled hypertension (CH). MUCH was defined as having controlled office BP and 24-hour ambulatory BP ≥ 130/80 mmHg and/or daytime BP ≥ 135/85 mmHg and/or nighttime BP ≥ 120/70 mmHg. Otherwise, patients were in the CH group7. Left ventricular mass (LVM) was assessed by echocardiography. The procedure was performed by a certified cardiologist using an American Philips Affiniti 50G ultrasound machine. LVM (g) was calculated by the equation 0.832 x [(IVSd + LVEDd + PWTd)³ – LVEDd³] + 0.6 (g) in which LVEDd: LV end-diastolic dimension (mm), IVSd: interventricular septal thickness at end-diastole (mm), PWTd: posterior wall thickness at end-diastole (mm). LVM index was expressed as LVMI = LVM/Body surface area (g/m²) in which body surface area = 0.007184 x W⁰.⁴²⁵ x H⁰.⁷²⁵ (m²) (W = Weight, H = Height). LVH was defined as LVMI ≥ 115 g/m² in men and LVMI ≥ 95 g/m² in women8. Serum creatinine and other laboratory tests were measured at Nhan Dan Gia Dinh Hospital. Quality control for laboratory testing complied with the regulations of the Vietnamese Ministry of Health. Grading of CKD was based on eGFR6.
Statistical analyses
Continuous variables with normal distribution were displayed as the means ± standard deviation (SD). Continuous variables with skewed distributions were presented as the medians (M25–M75). Shapiro–Wilk test of normality was used to determine the normal distribution of data. Categorical variables were presented by percentage (%) and compared using the Chi-squared test or Fisher’s exact test when appropriate. For continuous variables, we compared the average values of the two groups by Student’s t-test. In the case of a non-normal distribution, a Mann–Whitney non-parametric test was utilized. Univariate and multivariate logistic regression analyses were conducted to ascertain risk factors of LVH. Multivariate logistic regression analysis was done using confounders that were significant in the univariate model. Univariate and multivariate logistic regression analyses examined 1-SD changes in continuous variables. The presence of dichotomous variables was coded as 1 and the absence as 0. All probabilities were expressed as 2-tailed, with statistical significance inferred at P < 0.05. All confidence intervals were computed at the 95% level. Statistical analysis was done using STATA 20.0 (StataCorp, College Station, TX, USA).
Results
A total of 178 patients with CKD and controlled office BP completed the study. After assessing 24-hour ABPM, 87 patients had MUCH (48.9%) and 91 patients were in the CH group.
Baseline characteristics
Compared with patients with CH, those having MUCH had longer hypertension duration at baseline. There was no significant difference in CKD stages between the two groups. Notably, LVH was more prevalent in the MUCH group. All laboratory results did not have a statistically significant difference in the two groups (
Baseline characteristics according to BP groups
|
|
All (N = 178) |
MUCH (N = 87) |
CH (N = 91) |
P-value |
|
Age (year) |
68.2 ± 8.8 |
67.5 ± 9.2 |
68.8 ± 8.4 |
0.558 |
|
Male |
92 (51.7) |
41 (47.1) |
51 (56.0) |
0.294 |
|
BMI (kg/m2) |
24.4 ± 3.0 |
24 ± 3.2 |
24.7 ± 2.8 |
0.079 |
|
Current smoker |
24 (13.5) |
14 (16.1) |
10 (11.0) |
0.627 |
|
CKD staging | ||||
|
G3a G3b G4 G5 |
53 (29.8) 85 (47.8) 33 (18.5) 7 (3.9) |
23 (26.4) 42 (48.3) 18 (20.7) 4 (4.6) |
30 (33.0) 43 (47.3) 15 (16.5) 3 (3.3) |
0.738 |
|
Diabetes mellitus |
114 (64.0) |
55 (63.2) |
59 (64.8) |
0.876 |
|
Dyslipidemia |
162 (91.0) |
78 (89.7) |
84 (92.3) |
0.606 |
|
Stroke |
13 (7.3) |
6 (6.9) |
7 (7.7) |
0.999 |
|
Heart failure |
9 (5.1) |
5 (5.7) |
4 (4.4) |
0.743 |
|
Ischemic heart disease |
16 (9.0) |
7 (7.9) |
9 (4.4) |
0.704 |
|
HTN duration (year) |
9.5 ± 7.2 |
10.4 ± 7.1 |
8.5 ± 7.2 |
0.015 |
|
CKD duration (year) |
2.9 ± 2.9 |
3.1 ± 3.2 |
2.7 ± 2.4 |
0.953 |
|
Serum creatinine (mmol/L) |
138.4 (121.8-167.3) |
139.9 (129.1-172.6) |
134.6 (120.7-162.1) |
0.168 |
|
eGFR (ml/min/1.73 m2) |
37.4 ± 11.4 |
36.1 ± 12.1 |
38.7 ± 10.6 |
0.113 |
|
Cholesterol (mg/dL) |
170.0 ± 28.8 |
174.8 ± 59.3 |
165.3 ± 53.1 |
0.184 |
|
Triglyceride (mg/dL) |
171.7 (127.4-243.7) |
166.1 (128.7-252.2) |
172.2 (127.0-230.9) |
0.795 |
|
HDL-cholesterol (mg/dL) |
43.2 (37.3-48.2) |
43.6 (37.9-50.9) |
42.4 (36.9-47.1) |
0.280 |
|
LDL-cholesterol (mg/dL) |
82.8 (57.2-117.6) |
86.5 (59.2-116.4) |
80.7 (54.7-117.0) |
0.478 |
|
LVEF (%) |
68.9 ± 7.3 |
68.4 ± 8.4 |
69.3 ± 6.1 |
0.710 |
|
LVMI (g/m2) |
106.5 ± 28.8 |
110.4 ± 29.3 |
102.6 ± 27.8 |
0.095 |
|
LVH |
83 (46.6) |
48 (55.2) |
35 (38.5) |
0.025 |
|
ACE inhibitors |
30 (16.8) |
12 (13.8) |
18 (19.8) |
0.286 |
|
ARBs |
97 (54.5) |
49 (56.3) |
48 (52.8) |
0.632 |
|
Thiazides |
22 (12.3) |
9 (10.4) |
13 (14.3) |
0.425 |
|
Loop diuretics |
39 (21.9) |
20 (23.0) |
19 (20.9) |
0.734 |
|
CCBs |
122 (68.6) |
61 (70.1) |
61 (67.0) |
0.658 |
|
Beta blockers |
88 (49.4) |
43 (49.4) |
45 (49.5) |
0.997 |
Characteristics of MUCH in CKD patients
The difference between office and ambulatory BP in the two groups was statistically significant, with the BP values being higher in the MUCH group (
Blood pressure characteristics according to BP groups
|
Blood pressure (mmHg) |
All (n = 178) |
MUCH (n = 87) |
CH (n = 91) |
P-value |
|
Office SBP |
128.6 ± 6.2 |
130.4 ± 5.9 |
126.8 ± 6 |
< 0.001 |
|
Office DBP |
73.9 ± 7.0 |
75.6 ± 6.7 |
72.3 ± 7.0 |
0.002 |
|
24-hour |
118.7 ± 12.0 |
128.1 ± 8.1 |
109.6 ± 7.3 |
< 0.001 |
|
24-hour DBP |
66.7 ± 7.9 |
70.6 ± 7.9 |
63.0 ± 5.8 |
< 0.001 |
|
SBP day |
120.1 ± 11.5 |
128.3 ± 8.5 |
112.2 ± 8.0 |
< 0.001 |
|
DBP day |
67.8 ± 8.0 |
71.1 ± 8.2 |
64.7 ± 6.5 |
< 0.001 |
|
SBP night |
116.0 ± 14.7 |
128.0 ± 9.3 |
104.5 ± 8.3 |
< 0.001 |
|
DBP night |
64.9 ± 9.0 |
70.3 ± 8.6 |
59.8 ± 5.9 |
< 0.001 |
Univariate and multivariate logistic regression analyses
As shown in univariate analysis, CKD stage 4-5 and MUCH were associated with LVH (OR = 2.64, 95% CI: 1.29 – 5.61, P = 0.009 and OR = 1.97, 95% CI: 1.09 – 3.60, P = 0.026, respectively) (Table 3). Both factors remained statistically significant when included in multivariate analysis. Patients with CKD stage 4-5 had a higher risk of LVH (OR = 2.58; 95% CI: 1.16 – 5.94, P = 0.036) while MUCH patients were at increased risk of LVH two times higher (OR = 1.97; 95% CI: 1.03 – 3.85, P = 0.026) (
Univariate and multivariate regression analyses for factors associated with LVH in patients with CKD
|
Univariate |
Multivariate | |||||
|
OR |
CI 95% |
P-value |
OR |
CI 95% |
P-value | |
|
Age |
1.16 |
0.48 – 2.86 |
0.746 |
-- |
-- |
-- |
|
Male |
0.58 |
0.32 – 1.06 |
0.077 |
-- |
-- |
-- |
|
Current smoker |
1.34 |
0.72 – 2.51 |
0.359 |
-- |
-- |
-- |
|
Diabetes mellitus |
1.32 |
0.72 – 2.47 |
0.374 |
-- |
-- |
-- |
|
HTN duration ≥ 10 years |
1.16 |
0.64 – 2.11 |
0.622 |
-- |
-- |
-- |
|
RAAS inhibitors |
0.70 |
-1.00 – 0.29 |
0.286 |
-- |
-- |
-- |
|
Other HTN drugs |
1.88 |
-0.33 – 1.589 |
0.199 |
-- |
-- |
-- |
|
CKD staging 4-5 |
2.64 |
1.29 – 5.61 |
0.009 |
2.58 |
1.16 – 5.94 |
0.036 |
|
MUCH |
1.97 |
1.09 – 3.60 |
0.026 |
1.97 |
1.03 – 3.85 |
0.026 |
Discussion
We used daytime and/or nighttime and/or 24-hour BP values to define MUCH and confirmed the rate was 48.9%. Other studies demonstrated that the prevalence of MUCH in CKD patients ranges from 45.0 to 70.0% depending on diagnostic criteria3, 5, 9. All patients participating in this study had elevated nocturnal BP while only 11.8% had high daytime BP. This finding suggested that the routine use of office BP measurement and even home BP monitoring had a limited role in detecting MUCH in patients with CKD. Though 24-hour ABPM does not provide day-to-day BP variations, this is a favorable approach in clinical settings for BP evaluation.
The precise mechanism by which CKD elevates nocturnal BP involves complex processes, including volume-dependent hypertension exacerbated by serum sodium dysregulation, comorbidities like diabetes mellitus, and autonomic nervous dysfunction10, 11, 12. The dysfunction of endothelial cells lowers nitric oxide production causing suppression of the sympathetic nervous system13. Nocturnal hypertension is common in individuals with CKD due to disruptions in the body's circadian rhythm as well. Fukuda et al. suggested that decreased renal function reduces sodium excretion during the day and nighttime BP then rises to increase sodium clearance14.
Our results are similar to the AASKD report, in which participants with masked hypertension had higher LVH proportions than those with normal BP and white-coat hypertension3. In the CRIC study, masked hypertension was associated with increased LVMI and pulse wave velocity compared to those with truly controlled BP4. LVH in individuals with CKD results from increased volume and pressure loads. Factors such as activation of the RAAS, inhibition of nitric oxide synthesis, intravascular volume expansion, secondary anemia, and arteriovenous fistulas contribute to myocardial cell elongation and the development of eccentric or asymmetric LVH, potentially progressing to LV fibrosis15. Clinical evidence underscores the association between LVH, myocardial fibrosis, and heightened mortality risk, along with increased cardiovascular events in CKD and ESRD, as evidenced by elevated rates of sudden cardiac death15. Regression of left ventricular mass could serve as a valuable surrogate marker for assessing the benefits of RAAS inhibition aimed at reducing mortality risk in hypertensive patients16. Similar results were observed in the CKD population with the roles of proper hemoglobin targets and hemodialysis regimens in addition to RAAS inhibition17.
A remarkable insight of our study is the use of 24-hour ambulatory BP for diagnosing out-of-office hypertension and assessing the BP patterns of patients with CKD. The prevalence of MUCH in the CKD population was considerable. Moreover, our findings support that CKD patients with MUCH have a higher risk of left ventricular hypertrophy than those with CH. Further studies are needed to define this relationship clearly and whether targeting MUCH patients can reduce the adverse outcomes.
There are several limitations of our study. First, due to limited resources, we did not assess sleep quality and other essential factors, including lifestyle choices and socioeconomic status, which have been proven to affect nocturnal BP, CKD, and LVH and their relationships18. Second, the study did not include those with structural CKD stages 1 and 2. Third, the retrospective design might introduce selection and information biases, as data were obtained from medical records. Fourth, while a sample size of 178 patients is adequate, a larger cohort that includes regional variations in patient demographics could yield more robust data. Fifth, the accuracy measurements may be influenced by equipment limitations regarding ABPM devices and variations in operator technique during the heart ultrasound. Future research should overcome these limitations by incorporating multicenter designs, recruiting larger and more diverse populations, and conducting longitudinal follow-ups to validate these findings.
Conclusions
We recommend routinely using ABPM, which is sustainable in developing countries like Vietnam, to detect MUCH, especially nocturnal high blood pressure in CKD patients even with controlled office hypertension. Screening for LVH is necessary in those with MUCH.
Abbreviations
ABPM: Ambulatory Blood Pressure Monitoring, ACE: Angiotensin-Converting Enzyme, ARB: Angiotensin Receptor Blocker, BMI: Body Mass Index, BP: Blood Pressure, CCB: Calcium Channel Blocker, CH: Controlled Hypertension, CI: Confidence Interval, CKD: Chronic Kidney Disease, CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration, CRIC: Chronic Renal Insufficiency Cohort Study, DBP: Diastolic Blood Pressure, eGFR: Estimated Glomerular Filtration Rate, ESRD: End-Stage Renal Disease, HDL: High-Density Lipoprotein, HTN: Hypertension, LDL: Low-Density Lipoprotein, LVH: Left Ventricular Hypertrophy, LVEF: Left Ventricular Ejection Fraction, LVM: Left Ventricular Mass, LVMI: Left Ventricular Mass Index, MUCH: Masked Uncontrolled Hypertension, OR: Odds Ratio, RAAS: Renin-Angiotensin-Aldosterone System, SBP: Systolic Blood Pressure, SD: Standard Deviation
Acknowledgments
None.
Author’s contributions
All authors equally contributed to this work, read and approved the final manuscript.
Funding
None.
Availability of data and materials
Data and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate
The study was approved by the ethics committee of the University of Medicine and Pharmacy at Ho Chi Minh City (No. 373/IRD/UMP, October 25, 2018) and written informed consent was obtained from all patients prior to enrollment. The investigation conformed to the principles outlined in the 1975 Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.