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Bladder overactivity and post-void residual: Which relates more to systemic atherosclerotic markers?

Published:November 18, 2019DOI:https://doi.org/10.1016/j.autneu.2019.102600

      Abstract

      Objective

      Several studies have shown relationship between the lower urinary tract dysfunction (LUTD) and atherosclerosis. However, no study is available to see which LUTD relates more to atherosclerosis, among detrusor overactivity and post-void residual. In order to answer this question, we present data of urodynamic and atherosclerosis tests.

      Methods

      We performed standard urodynamics and two atherosclerosis tests, i.e., a cardio-ankle vascular stiffness index (CAVI) test and a duplex carotid ultrasonography.

      Patients

      We have 183 patients; 109 men (mean age 66.3 years), 74 women (mean age 66.4 years); all age > 60 years.

      Results

      Detrusor overactivity is related with high CAVI value (p < 0.05) but not with carotid intima-media thickness. Post-void residuals did not show such relation.

      Conclusion

      Urodynamic LUTD, particularly detrusor overactivity that may indicate central etiology is positively related with systemic atherosclerosis as measured by CAVI. Post-void residuals that may indicate peripheral etiology did not show such relation.

      1. Introduction

      Age-related systemic atherosclerosis is a significant burden for cardiovascular, cerebrovascular and kidney diseases as well as cognitive, gait and bladder disorders (
      • Zacche M.M.
      • Giarenis I.
      • Thiagamoorthy G.
      • Robinson D.
      • Cardozo L.
      Is there an association between aspects of the metabolic syndrome and overactive bladder? A prospective cohort study in women with lower urinary tract symptoms.
      ). Among these, except for stress urinary incontinence, bladder dysfunction is comprised of overactive bladder (OAB, urinary urgency, frequency, with/without incontinence) (originating from central etiology, outlet obstruction, or both) (
      • Zacche M.M.
      • Giarenis I.
      • Thiagamoorthy G.
      • Robinson D.
      • Cardozo L.
      Is there an association between aspects of the metabolic syndrome and overactive bladder? A prospective cohort study in women with lower urinary tract symptoms.
      ) and/or large post-void residuals (PVR) (originating from outlet obstruction, underactive bladder, or both) (
      • Smith P.P.
      • Birder L.A.
      • Abrams P.
      • Wein A.J.
      • Chapple C.R.
      Detrusor underactivity and the underactive bladder: symptoms, function, cause-what do we mean? ICI-RS think tank 2014.
      ). There is an abundant literature to show relationship between the lower urinary tract dysfunctions (LUTD) associated with atherosclerosis (e.g. metabolic syndrome, chronic pelvic ischemia, etc.). However, thus far no study has been available to see which type of bladder disorder relates more to atherosclerosis. In order to answer this question, we present data of bladder autonomic and physiology tests.

      2. Methods

      This is a retrospective study during a one-year period from April 2017 to March 2018. Inclusion criteria were: 1) patients who visited Clinical Physiology Unit at our university because of their lower urinary tract symptoms by a bladder questionnaire (LUTS; OAB and/or voiding difficulty, the latter is sometimes unrecognized even by the patient), 2) patients who underwent urodynamics because of LUTS, 3) patients who had atherosclerotic risks, e.g., at least one of hypertension, dyslipidemia, obesity, smoking, etc., and 4) patients who underwent two atherosclerotic tests, i.e., a cardio-ankle vascular stiffness index (CAVI) test and a duplex carotid ultrasonography because of atherosclerotic risks.
      Exclusion criteria were: 1) men who had prostate volume > 30 ml by an ultrasound echography. We did not perform other tests such as abdominal CT/MRI, 2) patients who are taking drugs that might affect bladder function, 3) patients who have urinary tract infection, stones, etc., and 4) patients who are not suitable to perform the tests, e.g., those who had severe dementia, etc.
      Urodynamics was performed according to the International Continence Society standards. A double-lumen 8F catheter (for use with saline infusion and intra-vesical pressure measurements) was inserted into the bladder. We performed simple medium-fill (50 ml/min) electromyography (EMG)-cystometry with a urodynamic computer (Urovision; Lifetech Inc., Houston, TX, USA) and an electromyographic computer (Neuropack M2; Nihon Kohden Inc., Tokyo, Japan), simultaneously recording the detrusor pressure, which is the difference between the intra-vesical and intra-abdominal (rectal) pressures, the sphincter electromyography (EMG) via a concentric needle electrode in the external anal sphincter muscle, and the urinary flow via uroflowmeter. We did not perform urethral profilometry. A pressure-flow analysis was performed to the extent possible in the patients who were able to void. They were 73patients (41 men and 28 women). Among them, 40 men (37%) and 21 women (28%) was plotted as having underactive detrusor (Schafer's weak/very weak). None was plotted as having apparent outlet obstruction (Schafer's obstruction grade 3–6).
      A cardio-ankle vascular stiffness index (CAVI) test was performed by a VaSera CAVI instrument (Fukuda Denshi Inc., Tokyo, Japan) (
      • Yeniel A.O.
      • Ergenoglu A.M.
      • Meseri R.
      • Kismali E.
      • Ari A.
      • Kavukcu G.
      • Aydin H.H.
      • Ak H.
      • Atay S.
      • Itil I.M.
      Is overactive bladder microvasculature disease a component of systemic atheroscleorosis?.
      ). CAVI was calculated by the following formula: CAVI = a{(2ρ/ΔP) × ln(Ps/Pd)PWV2} + b, where Ps is systolic blood pressure, Pd is diastolic blood pressure, PWV is pulse wave velocity, ΔP is Ps − Pd, ρ is blood density, and a and b are constants (
      • Suzuki J.
      • Sakakibara R.
      • Tomaru T.
      • Tateno F.
      • Kishi M.
      • Ogawa E.
      • Kurosu T.
      • Shirai K.
      Stroke and cardio-ankle vascular stiffness index.
      ). The average coefficient of variation of CAVI is <5%, which is small enough for clinical usage and indicates that CAVI has good reproducibility (
      • Suzuki J.
      • Sakakibara R.
      • Tomaru T.
      • Tateno F.
      • Kishi M.
      • Ogawa E.
      • Kurosu T.
      • Shirai K.
      Stroke and cardio-ankle vascular stiffness index.
      ). A duplex carotid ultrasonography was performed with the linear-array 7.5-MHz transducers (EUB-525, Hitachi, Inc., Tokyo, Japan; SSA-260A, Toshiba, Inc., Tokyo, Japan). We then measured intima-media thickness (IMT). Statistics was analyzed by Students' t-test and Mann-Whitney's U test. Before participating in the study, informed consent was obtained in all subjects. This study was approved by the local Ethics Committee.

      3. Results

      We recruited 183 patients; 109 men (mean age 66.3 years), 74 women (mean age 66.4 years); all age > 60 years. Among these, urodynamics showed that 76 patients had detrusor overactivity; 37 patients had post-void residual volume > 100 ml by transurethral catheterization; and the remaining 70 patients had neither detrusor overactivity or post-void residual volume > 100 ml and they were served as controls.
      As a result of the detailed relation analysis between bladder autonomic and physiology tests, there was no relationship between A) IMT and CAVI, and B) urodynamic parameters including maximum and average urinary flow, first sensation, maximum bladder capacity and underactive detrusor.
      In contrast, there was a significant relationship between detrusor overactivity (total) and CAVI (p < 0.05) (Fig. 1). The same finding was noted in men (p < 0.05) while it was not noted in women. There was no relationship between detrusor overactivity and IMT. There was no relationship between large PVR > 100 ml and CAVI or IMT. There was no relationship between stratified detrusor overactivity (phasic type and terminal type; with detrusor pressure increase <30 cmH2O and >30 cmH2O; with large PVR and without large PVR; with concurrent underactive detrusor and without concurrent underactive detrusor) and CAVI or IMT (Table 1).
      Fig. 1
      Fig. 1Relationship between large PVR > 100 ml/DO and CAVI/IMT.
      PVR > 100 ml: post-void residual urine volume > 100 ml (normal < 30 ml).
      DO: detrusor overactivity.
      CAVI: cardio-ankle vascular stiffness index: a larger number indicates higher stiffness.
      IMT: intima-media thickness: a larger number indicates thicker.
      Horizontal bar indicates normal value.
      Table 1Patients and underlying diseases.
      DiseaseControlLarge PVR > 100 mlDetrusor overactivityTotal
      Parkinson's disease2022446
      Dementia with Lewy bodies (early)61613
      White matte-type cerebral infarction95519
      Progressive supranuclear palsy1135
      Spinocerebellar ataxia type 32002
      Spinocerebellar ataxia type 681211
      Diabetes45312
      Cervical spondylosis1001
      Lumbar spondylosis1124
      Alzheimer's disease (early)2125
      Rectal carcinoma, postsurgery1001
      Pure autonomic failure1135
      Urinary incontinence1012
      Neurogenic bladder dysfunction53412
      Sarcoidosis1001
      Spinocerebellar degeneration, sporadic2114
      Multiple system atrophy-cerebellar type24612
      Multiple system atrophy-parkinsonian type25512
      Peripheral neuropathy1102
      Meningitis-retention syndrome0101
      Normal pressure hydrocephalus0033
      Myelitis0011
      Unknown0459
      Total703776183

      4. Discussion

      Previously, Uzun and colleagues reported a relationship between IMT/abnormal pulse wave velocity with urinary urgency and voiding difficulty (by a questionnaire, no urodynamics) (
      • Uzun H.
      • Çiçek Y.
      • Kocaman S.A.
      • Durakoğlugil M.E.
      • Zorba O.
      Increased pulse-wave velocity and carotid intima-media thickness in patients with lower urinary tract symptoms.
      ). In contrast, Hsiao and colleagues reported no association between CAVI and urinary urgency (by a questionnaire, no urodynamics) (
      • Hsiao S.M.
      • Su T.C.
      • Chen C.H.
      • Chang T.C.
      • Lin H.H.
      Autonomic dysfunction and arterial stiffness in female overactive bladder patients and antimuscarinics related effects.
      ). To our knowledge, this is the first urodynamic study to show that detrusor overactivity positively related with atherosclerosis as measured by CAVI, while large PVR > 100 ml did not. The exact reasons for these findings remain unclear. However, it is generally thought that, among bladder dysfunction, OAB/detrusor overactivity originates from central etiology (loss of brain's inhibition on the bladder), outlet obstruction, or both (
      • Zacche M.M.
      • Giarenis I.
      • Thiagamoorthy G.
      • Robinson D.
      • Cardozo L.
      Is there an association between aspects of the metabolic syndrome and overactive bladder? A prospective cohort study in women with lower urinary tract symptoms.
      ). In contrast, large PVR mostly originates from outlet obstruction, underactive bladder (loss of bladder innervations etc.), or both (
      • Smith P.P.
      • Birder L.A.
      • Abrams P.
      • Wein A.J.
      • Chapple C.R.
      Detrusor underactivity and the underactive bladder: symptoms, function, cause-what do we mean? ICI-RS think tank 2014.
      ). The underlying etiologies of detrusor overactivity in our patients vary significantly. However, except for multiple system atrophy which commonly causes both detrusor overactivity and underactive bladder (so called DHIC), most patients with detrusor overactivity have central nervous system disorders (
      • Sakakibara R.
      • Panicker J.
      • Fowler C.J.
      • Tateno F.
      • Kishi M.
      • Tsuyusaki Y.
      • Yamanishi T.
      • Uchiyama T.
      • Yamamoto T.
      • Yano M.
      Is overactive bladder a brain disease? The pathophysiological role of cerebral white matter in the elderly.
      ;
      • Yeniel A.O.
      • Ergenoglu A.M.
      • Meseri R.
      • Kismali E.
      • Ari A.
      • Kavukcu G.
      • Aydin H.H.
      • Ak H.
      • Atay S.
      • Itil I.M.
      Is overactive bladder microvasculature disease a component of systemic atheroscleorosis?.
      ), while most patients with large PVR have peripheral nervous system disorders (
      • Smith P.P.
      • Birder L.A.
      • Abrams P.
      • Wein A.J.
      • Chapple C.R.
      Detrusor underactivity and the underactive bladder: symptoms, function, cause-what do we mean? ICI-RS think tank 2014.
      ). Whereas we could not completely exclude outlet obstruction, from the view point of the bladder disorder, atherosclerosis might have significant impact on the brain.
      Limitation of the present study obviously includes a small sample size; possible confounders such as comorbidities, previous urological surgery, medications, etc., and no stratification with age. Nevertheless, our study results facilitate further studies to clarify atherosclerotic role on the elderly bladder problem. There is a debate as to why there was a significant relationship between detrusor overactivity and CAVI in men, but not in women in the present study. One possibility is due to a small sample size. The other possibility is that, while gender did not contribute to either detrusor overactivity or CAVI significantly in the previous studies, female gender might have lessened CAVI as suggested by a recent paper (
      • Emi Y.
      • Adachi M.
      • Sasaki A.
      • Nakamura Y.
      • Nakatsuka M.
      Increased arterial stiffness in female-to-male transsexuals treated with androgen.
      ,
      • Hsiao S.M.
      • Su T.C.
      • Chen C.H.
      • Chang T.C.
      • Lin H.H.
      Autonomic dysfunction and arterial stiffness in female overactive bladder patients and antimuscarinics related effects.
      ,
      • Osman N.I.
      • Esperto F.
      • Chapple C.R.
      Detrusor underactivity and the underactive bladder: a systematic review of preclinical and clinical studies.
      ,
      • Sakakibara R.
      • Panicker J.
      • Fowler C.J.
      • Tateno F.
      • Kishi M.
      • Tsuyusaki Y.
      • Yamanishi T.
      • Uchiyama T.
      • Yamamoto T.
      • Yano M.
      Is overactive bladder a brain disease? The pathophysiological role of cerebral white matter in the elderly.
      ,
      • Smith P.P.
      • Birder L.A.
      • Abrams P.
      • Wein A.J.
      • Chapple C.R.
      Detrusor underactivity and the underactive bladder: symptoms, function, cause-what do we mean? ICI-RS think tank 2014.
      ,
      • Suzuki J.
      • Sakakibara R.
      • Tomaru T.
      • Tateno F.
      • Kishi M.
      • Ogawa E.
      • Kurosu T.
      • Shirai K.
      Stroke and cardio-ankle vascular stiffness index.
      ,
      • Uzun H.
      • Çiçek Y.
      • Kocaman S.A.
      • Durakoğlugil M.E.
      • Zorba O.
      Increased pulse-wave velocity and carotid intima-media thickness in patients with lower urinary tract symptoms.
      ,
      • Vale L.
      • Jesus F.
      • Marcelissen T.
      • Rieken M.
      • Geavlete B.
      • Rahnama’i M.S.
      • Martens F.
      • Cruz F.
      • Antunes-Lopes T.
      • EAU Young Academic Urologists Functional Urology Working Group
      Pathophysiological mechanisms in detrusor underactivity: novel experimental findings.
      ,
      • Yeniel A.O.
      • Ergenoglu A.M.
      • Meseri R.
      • Kismali E.
      • Ari A.
      • Kavukcu G.
      • Aydin H.H.
      • Ak H.
      • Atay S.
      • Itil I.M.
      Is overactive bladder microvasculature disease a component of systemic atheroscleorosis?.
      ,
      • Zacche M.M.
      • Giarenis I.
      • Thiagamoorthy G.
      • Robinson D.
      • Cardozo L.
      Is there an association between aspects of the metabolic syndrome and overactive bladder? A prospective cohort study in women with lower urinary tract symptoms.
      ). In addition, the mechanism of underactive detrusor includes 1) intrinsic detrusor muscle change by ageing, 2) secondary phenomenon by prolonged DO particularly in outlet obstruction, and 3) neural damage in the peripheral nerves (diabetes, lumbar spondylosis, etc.) and/or spinal cord (DHIC as described above) (
      • Osman N.I.
      • Esperto F.
      • Chapple C.R.
      Detrusor underactivity and the underactive bladder: a systematic review of preclinical and clinical studies.
      ;
      • Vale L.
      • Jesus F.
      • Marcelissen T.
      • Rieken M.
      • Geavlete B.
      • Rahnama’i M.S.
      • Martens F.
      • Cruz F.
      • Antunes-Lopes T.
      • EAU Young Academic Urologists Functional Urology Working Group
      Pathophysiological mechanisms in detrusor underactivity: novel experimental findings.
      ). Among these, we could not answer the mechanism of prolonged DO. This is because we excluded apparent outlet obstruction, and there was no relationship between stratified detrusor overactivity (with concurrent underactive detrusor and without concurrent underactive detrusor) and CAVI or IMT in the present study. Therefore, in order to clarify the mechanism of prolonged DO with underactive detrusor, we need further studies.
      In conclusion, bladder autonomic dysfunction, particularly urodynamic detrusor overactivity that indicates central etiology, is positively related with systemic atherosclerosis as measured by CAVI. Post-void residuals did not show such relation.

      Declaration of competing interest

      None of the authors have any conflicts of interest to declare.

      Acknowledgments

      We appreciate great collaboration with Ms. Ayami Shimizu and Osamu Takahashi in the Clinical Physiology Unit, Sakura Medical Center, Toho University, Sakura, Japan.

      Author contributions

      Ryuji Sakakibara has a role in: study concept and design, acquisition of subjects and/or data, analysis and interpretation of data, and preparation of manuscript.
      Fuyuki Tateno has a role in: acquisition of data.
      Yosuke Aiba has a role in: acquisition of data.
      Tsuyoshi Ogata has a role in: acquisition of data.

      Sponsor's role

      We had no sponsors.

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