The relationship between the central arterial stiffness and the degree of nocturia in men

YUEN K1, CHAN C1, NG C1, TEOH Y1, YEE C1, CHIU K1, WONG H1, TAM H1, CHAN Y1, WONG H1, HOU S1, MAK S1, LO K1, LI K1, WONG C1, LEUNG K1, LI S1, KWOK S2, SAE LO K2

Research Type

Clinical

Abstract Category

Nocturia

Abstract 3
Best Urology
Scientific Podium Session 1
Wednesday 4th September 2019
09:30 - 09:45
Hall K
Nocturia Male Benign Prostatic Hyperplasia (BPH) Pathophysiology Gerontology
1.SH HO Urology Centre, Division of Urology, Dept of Surgery, The Chinese University of Hong Kong, 2.Prince of Wales Hospital, The Chinese University of Hong Kong
Presenter
K

Kar Kei Steffi Yuen

Links

Abstract

Hypothesis / aims of study
Common  urological conditions in men such as lower urinary tract symptoms (LUTS), erectile dysfunction (ED) and nocturia are alluded to sharing the same aetiologies (i.e. endothelial dysfunction / atherosclerosis) with the lethal vascular diseases like acute coronary syndrome (ACS), acute myocardial infarction (AMI), carotid artery stenosis, non-cardioembolic stroke and/or peripheral vascular disease (PVD).
Central artery stiffness (CAS)  is highly correlated with the degree of systemic atherosclerosis and is linked to the occurrence of the aforesaid cardiovascular (CV) events with remarkable predictive power [1][2]. For the past decade, CAS can be reasonably quantified by brachial-ankle pulse wave velocity (baPWV) measurement using oscillometric method, which is acclaimed for its non-invasive nature, ease of use by staff, reproducibility, strong prediction for the subsequent CV events and wide acceptance by the patients [1].  
We hypothesize that baPWV is also correlated with the aforementioned urological conditions in men. In view of the scarce availability of the pertinent data to date, this study is conducted to explore the relationships between baPWV and LUTS, ED, as well as nocturia in men, for whom CV events are common as they are aging.
Study design, materials and methods
This cross-sectional study enrolled consecutive men from new referrals to the general urology clinic for the problem(s) of LUTS / ED / Nocturia. At the outpatient clinic, they were informed of the purpose and the running of the study, and then invited to participate in the study. After they had given the consent, they filled out both IPSS and IIEF-5 questionnaires, underwent uroflowmetry / post-void residual estimation by the bladder scan, and then rested in supine position for 10 minutes followed by measurement of their bilateral baPWV and ankle-brachial index (ABI) with the use of the automatic device {pulse waveform analyzer, model BP-203RPE-III; Nihon Colin, Tokyo, Japan}. 
In brief,  the baPWV was measured simply by wrapping blood pressure cuffs on the 4 extremities and calculated as the ratio of the virtual arterial path length derived from the height of the men and the time difference between the commencements of systolic increases in brachial and ankle pressure waves.  The test was repeated for 3 times and the parameters were then averaged to give the final values of the measurements. Exclusion criteria included men having aortic aneurysm, marked cardiac arrhythmia, severe PVD or low body temperature(<36C).
Previous studies showed that the baPWV is correlated to age with R ~ 0.4 - 0.6 [1[[2][3]. We hypothesize that baPWV is correlated to LUTS/ED/Nocturia with R ~ 0.16 - 0.20. Sample size calculation showed that ~240 subjects (α=0.05 ; β=0.80) had to be recruited for the study. History of diabetes mellitus (DM), ischaemic heart (IHD), and hypertension (HT) was also taken into account for the analysis.  
Test for bivariate correlation coefficients among the continuous variables, parametric ANOVA test {with post-hoc tests (Tukey/Duncan)} / non-parametric Kruskall-Wallis test for comparing continuous data of multiple groups, and Chi-square / Fisher-Exact tests for categorical variables are performed, where appropriate. 
Variables are also dichotomized and analysed by multivariate logistic regression using stepwise backward LR method to determine the factor(s) rendering the men to have baPWV>1800cm/s, a cut-off value that is highly associated with later CV events [1][2]. 
Statistical analysis is performed using IBM SPSS-V.24 statistical package. Statistical significance is taken when p<0.05 and shown in RED or GREEN colour in the figure and table attached.
Results
246 men (mean age 68, range:36–88) were recruited. Descriptive characteristics of the subjects are tabulated in Table 1(a). The men are stratified into 4 groups according to their age (<70 vs >=70) and degree of nocturia (<=2 vs >2) for comparison.  
Of all the variables listed, baPWV is positively correlated with the age (R: right=0.41, left=0.37, p<0.0001) and the number of nocturia per night (R: right=0.16, left=0.17, p<0.01); whereas it is negatively correlated with the weight (R: right= -0.17, left= -0.15, p<0.01),  the height  (R: right= -0.26, left= -0.24, p<0.0001),  IIEF-5 (total score) (R: right= -0.16, left= -0.17, p< 0.01) and the voided volume (R: right= -0.19, left= -0.20, p<0.01) respectively. 
In contrast, ABI on both sides are neither correlated to any LUTS/ED/Nocturia symptoms nor to any history of DM / HT / IHD. However, left side ABI is correlated positively to some arthropometric parameters, namely body weight (R=0.152, p-0.017) and BMI (R=0.140, p=0.028), whereas right side ABI is correlated positively to the amount of voided volume (R=0.143, p=0.025). Both ABI appeared to be negatively correlated with the age (R: right= -0.119, p=0.063; left= - 0.121, p=0.058). 
Figure 1 shows that baPWV significantly increases (i.e. worsening CAS)  with nocturia in men<70yo {ANOVA, F(2,136), p=0.017}, yet they are not closely linked in the older men (>=70yo) {ANOVA, F(2,104), p=0.781}. Nonetheless,  baPWV of men(>=70yo) are higher than that of the men(<70yo) across mild to moderate degree of nocturia yet their differences are getting closer with the severity of nocturia and indistinct for the nocturia more than 4 times per night {Figure 1(a)&(b)}.  
Multivariate logistic regression analysis {Table 1(b)} shows that age (OR: 2.70, 95%CI: 1.52-4.76), DM (OR: 2.26, 95%CI: 1.06-4.83), hypertension (OR: 1.95, 95%CI 1.10-3.45) and nocturia{>2 per night} (OR: 1.75, 95%CI: 1.02-3.12) are the independent determining factors for baPWV >1800cm/s in our cohort.
Interpretation of results
The (mean ± SEM) baPWV (~1820 ± 16 cm/sec) of our cohort is significantly higher than the previously reported value of the general population of similar age structure (~1650 cm/sec) by ~10% [3] ,  implying that vasculopathy appears more extensive in men with LUTS / ED / Nocturia in our cohort, in which age, history of DM / HT and nocturia more than 2 times per night are the independent factors predicting baPWV suggestive of risky central arterial stenosis {CAS} (i.e. baPWV>1800 cm/sec).
In contrast, arthropometric parameters (weight, height, BMI, waist circumference), severe erectile dysfunction (IIEF-5 total score <=7), severe LUTS (IPSS>=20), results of uroflowmetry and ABI are not independent factors for determining risky CAS. 
Indeed, among the constellations of LUTS and ED symptoms, independent association is only seen between baPWV and nocturia, being strongest in men<70yo in our study. Of note, the findings (Figure 1) also infer that men<70yo with nocturia >=4/night may already have had CAS similar to that of the men 10 years older, suggesting that their arteries are "aging" faster than expected  and probably prognosticating them to develop CV events sooner than the men of the same age in the general population. 
These results suggest that the degree of the nocturia in men, particularly for those <70yo, may serve as an additional indicator for their vascular health, apart from the demographic data like age and history of DM / HT.
Given the design of the current study, we are not able to conclude any "cause and effect" connection between nocturia  and the vasculopathy, nor to determine any reversibility of the risky CAS in men<70yo with severe nocturia. Therefore, further longitudinal studies are much in need to answer the above questions.
Concluding message
Brachial-ankle pulse wave velocity {hence central arterial stiffness (CAS)} is correlated positively with the degree of the nocturia in men. This association is most notable when they are younger than 70 years of age. Nocturia more than 2 times per night in men is also linked to risky level of CAS predisposing to later cardiovascular events.
Figure 1 The variation of baPWV (cm/sec) in men across the different degree of nocturia stratified by age (<70yo vs >=70yo). Fig.1(a) RIGHT side; FIg 1(b) LEFT side
Figure 2 Table showing demographic characteristics of the men 1(a) and multivariate logistic regression analysis for factors determing baPWV >1800 cm/sec 1(b)
References
  1. Matsui S, Kajikawa M, Maruhashi T et al., Int J Cardiol 2018; 261: 196 - 203
  2. Maruhashi T, Soga J, Fujimura N, et al., J Am Heart Assoc. 2018 Jul 12;7(14). pii: e008588.
  3. Tomiyama H, Yamashina A, Arai T, et al., Atherosclerosis. 2003 Feb;166(2):303-9.
Disclosures
<span class="text-strong">Funding</span> Research Grant, Division of Urology, Department of Surgery, The Chinese University of Hong Kong <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> The Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (The Joint CUHK-NTEC CREC) <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes