The impact of atherosclerosis on lower urinary tract function

Abstract

Objective: The current study was carried out to investigate the impact of atherosclerosis on lower urinary tract function in the male patients with lower urinary tract symptoms (LUTS).

Patients and methods: This prospective study evaluated 110 male patients aged 55–75 years who were presented with LUTS. All patients underwent general and local investigations. The atherosclerosis was assessed by ultrasound examination of the carotid artery. Patients then were divided into two groups: non-atherosclerosis group (Group 1) and atherosclerosis group (Group 2). The two groups were compared regarding voiding and storage parameters.

Results: Mean patient age were 67.9 ± 5.9 years. The average age and number of Group 1 was 65.7 ± 4.3, n = 51. The average age and number of Group 2 was 68.7 ± 5.3, n = 59. There were no significant differences in age, prostate volume, blood pressure, International Prostate Symptom Score, Voiding symptom score and Storage symptom score between the two groups. Blood serum triglycerides were significantly lower in Group 1 than Group 2 while HDL cholesterol were significantly higher in Group 1 than Group 2 0.97 ± 0.5 and 1.43 ± 0.2 mmol/L, versus 1.46 ± 0.7 and 1.28 ± 0.3 mmol/L, respectively. Qmax denotes significant decrease in Group 2 compared with Group 1 12.5 ± 6.3 versus 17.6 ± 6.5, respectively (p < 0.01). While in post-voiding residual urine, there was a significant increase in Group 2 compared with Group 1 82.2 ± 15.4 versus 51.4 ± 12.7, respectively (p < 0.01). Daytime voided urine denotes a significant decrease in Group 2 176 ± 48, compared with Group 1 221.2 ± 79 (p < 0.01). Daytime frequency and nocturia, were significantly higher in Group 2, compared with Group 1 8.90 ± 2.8 versus 7.16 ± 3.11, respectively, and 3.1 ± 1.2 versus 1.92 ± 1.12, respectively (p < 0.05).

Conclusion: The atherosclerosis disease play a significant role in the impairments of both voiding and storage function in male patients with LUTS irrelevant to the age.

• Atherosclerosis
• carotid intima-media thickness
• LUTS

Introduction

Lower urinary tract symptoms (LUTS) are common complaints among aging men. These symptoms are often caused by benign prostatic hyperplasia, and include nocturia, urinary frequency, urgency, decreased urine flow rates, incomplete bladder emptying and hesitancy. These symptoms are common and their prevalence increases as men age [1,2].

The storage subcategory of LUTS is synonymous with overactive bladder syndrome (OAB), defined by the International Continence Society, as urgency, with or without urge incontinence, usually accompanied by increased daytime frequency and nocturia [3]. The OAB is a serious health problem because of its high prevalence and its significantly associated burden. The EPIC study reported that the overall prevalence of OAB is 12%, with similar rates in men and women, and that the prevalence of OAB increases with age [4]. Thus, male LUTS cannot be simply characterized as a prostate specific disease.

As any organ in the body, the urinary bladder needs a sufficient blood supply to gain oxygen and nutrition to function adequately. Ischemia associated with hypoxia would expect to impair bladder function [5]. Multiple evidences have established that ischemia, hypoxia and oxidative stress caused by that arterial occlusive disease such as atherosclerosis are significant etiologic factors in obstructive bladder dysfunction [6].

Ponholzer et al. [7] recorded the association of the most important vascular risk factors (diabetes mellitus, hypertension, nicotine abuse and hyperlipidemia) and LUTS in both women and men. According to their study, in men, the International Prostate Symptom Score (IPSS) was indistinguishable from those with no or one vascular risk factor, yet considerably increased in those with two or more risk factors. This study revealed the possibility that atherosclerosis act as a significant factor in the development of male LUTS.

Lin et al. [8] reported that chronic ischemia of the bladder lead to a decrease of bladder compliance with impairment in the contractility of the entire bladder. He also, established that chronic ischemia disturbed glucose metabolism of the detrusor with a diminution in glycogen content and an increase in anaerobic metabolism, resulting in a great decrease in production of high-energy molecules [9]. Using an atherosclerosis rabbit model, a recent study [10] also verified that chronic ischemia of the urinary bladder resulted in mitochondrial injury, fibrosis, microvasculature damage and neurodegeneration.

Recently, non-invasive measurements of arterial intima-media thickness (IMT) have been commonly used for assessment of subclinical arterial alterations, and have established that this is a predictor of cardiovascular disease CVD [11]. Carotid intima-media thickness (CIMT), as assessed using B-mode ultrasound, is a subclinical marker of atherosclerosis. Moreover, measurement of atherosclerotic plaque in the carotid artery is of great value in assessing changes in atherosclerotic burden over time [12,13].

The current study was carried out to investigate the impact of atherosclerosis on the lower urinary tract function in the male patients with LUTS.

Patients and methods

This prospective study was performed for 110 male patients aged 55–73 years, who came to the outpatient clinic between January 2010 and June 2012 with symptoms and signs suggesting (LUTS).

The project was previously approved by the Institution’s Research Ethics Committee. Informed consent was obtained from all participants

All patients underwent detailed medical history and current medication. Clinical examination (general and local) was carried out including digital rectal examination (DRE), blood pressure, serum prostate-specific antigen (PSA), serum cholesterol and lipids profile.

Exclusion criteria included the patients who had diabetes mellitus, bladder disease (tumours, stones and neurogenic bladder) and urethral stricture, previous history of prostatic surgery or biopsy and prostate cancer. Also, patients with abnormal findings during DRE of prostate and patients with previous intake of medical treatment of LUTS were excluded.

Each patient underwent routine investigation including prostatic volume measurement (mL) using pelvic ultrasound, uroflowmetry and measurement of post-voiding residual urine (PVR).

In addition, a 2-day frequency volume chart (FVC) was evaluated, which reported the voiding times, volume voided and urgency episodes.

The presence of urgency episodes at least once during a 2-day FVC was diagnosed as urgency.

All the subjects were assessed using IPSS. In addition, the IPSS subscores, including voiding symptom score (the sum of intermittency score, straining score and weak stream score) and storage symptom score (the sum of urgency score, frequency score and nocturia score)

Carotid artery intima-media thickness was used to diagnose the atherosclerosis, (Figure 1). It was measured by ultrasonography using a 7.5-MHz linear array transducer, with a frequency range of 7–10 MHz. Thickness measurements were performed bilaterally at the level of the common carotid artery far wall and always in stenotic-free segments, as previously reported [12]. For each subject, three measurements on both sides were performed, i.e. the anterior, lateral and posterior projection of the near and far wall. All readings were then averaged. A carotid plaque was defined as a focal thickening ≥1.2 mm at the level of carotid artery [13].

Figure 1. Ultrasound image of carotid artery. CIMT (carotid intima-media thickness). (A) No plaque, no CIMT thickness (no atherosclerosis). (B) CIMT, carotid plaque (atherosclerosis).

Patients were classified into two groups, the non-atherosclerosis group (Group 1) (no plaque or plaque <1.2 mm). And atherosclerosis group (Group 2) (with carotid plaque ≥1.2 mm) comparisons were performed between the two groups in the different parameters obtained.

Statistical analysis

Data are presented as means ± standard deviation. Statistical analyses included unpaired t test. p Values <0.05 were considered statistically significant

Results

The enrolled patients were 110 male patients with LUTS, their mean age was 67.9 ± 5.9 years. The patients’ data were shown in Table 1. The average age and number of Group 1 was 65.7 ± 4.3, n = 51, respectively. The average age and number of Group 2 was 68.7 ± 5.3, n = 59, respectively. Average prostate volume of Group 1 and Group 2 were 30.5 ± 9.3 and 29.7 ± 10.1, respectively. Mean IPSS in Group 1 and Group 2 were 12.8 ± 8.1 and 14.5 ± 8.8, respectively. The voiding symptom score and Storage symptom score in Group 1 and Group 2 were 5.9 ± 5.5 versus 5.1 ± 5.6 and 7.9 ± 4.8 versus 8.4 ± 4.9, respectively. Systolic and diastolic blood pressure (BP) of Group 1 and Group 2 were 132 ± 18 versus 135 ± 15 mmHg and 85 ± 8.1 versus 87 ± 9.1 mmHg, respectively. Urgency and nocturia, were 42.5% and 46.2% in Group 2, respectively, versus 21.2% and 26% in Group 1, respectively, and these difference were statistically significant (p < 0.001). Blood serum Triglycerides and HDL cholesterol in Group 1 were 0.97 ± 0.5 and 1.43 ± 0.2 mmol/L, respectively, versus 1.46 ± 0.7 and 1.28 ± 0.3 mmol/L, respectively, in Group 2 and these differences were statistically significant. While serum LDL cholesterol in Group 1 was 3.18 ± 0.3 mmol/L versus 3.20 ± 0.3 mmol/L in Group 2, with no significant difference. There were no significant differences in age, prostate volume, BP, IPSS, voiding symptom score and storage symptom score between the two groups.

Table 1. Patients’ data and criteria.

Patients’ data	Non-atherosclerosis group (Group 1)	Atherosclerosis group (Group 2)	p Value
Number	51	59	NS
Age (years)	65.7 ± 4.3	68.7 ± 5.3	NS
Prostate volume (mL)	30.5 ± 9.3	29.7 ± 10.1	NS
IPSS	12.8 ± 8.1	14.5 ± 8.8	NS
Voiding symptom score	5.9 ± 5.5	5.1 ± 5.6	NS
Storage symptom score	7.9 ± 4.8	8.4 ± 4.9	NS
Urgency	(21.2%)	(42.5%)	<0.001
Nocturia	(26%)	(46.2%)	<0.001
Systolic BP (mmHg)	132 ± 18	135 ± 15	NS
Diastolic BP (mmHg)	85 ± 8.1	87 ± 9.1	NS
Triglycerides (mmol/L)	0.97 ± 0.5	1.46 ± 0.7	<0.001
HDL cholesterol (mmol/L)	1.43 ± 0.2	1.28 ± 0.3	<0.01
LDL cholesterol (mmol/L)	3.18 ± 0.3	3.20 ± 0.3	NS

The findings obtained of Qmax denote significant lower in Group 2 compared with Group 1 12.5 ± 6.3 versus 17.6 ± 6.5, respectively (p < 0.01). While in PVR, there was significant increase Group 2 compared with Group 1 82.2 ± 15.4 versus 51.4 ± 12.7, respectively (p < 0.01) (Table 2).

Table 2. Viding and storage parameters.

	Non-atherosclerosis group (Group 1)	Atherosclerosis group (Group 2)	p Value
Maximum flow rate  (Qmax)	17.6 ± 6.5	12.5 ± 6.3	<0.01
Post-voiding residual  (PVR) (mL)	51.4 ± 12.7	82.2 ± 15.4	<0.01
Total daytime voided  urine (mL)	1690 ± 531	1622 ± 503	NS
Daytime voided  urine (mL)	221.2 ± 79	176 ± 48	<0.01
Daytime frequency	7.16 ± 3.11	8.90 ± 2.8	<0.05
Nocturia	1.92 ± 1.12	3.1 ± 1.2	<0.05

There was no significant difference in Total daytime voided urine between the two groups. While daytime voided urine denote significant decrease in Group 2 176 ± 48, compared with Group 1 221.2 ± 79 (p < 0.01). According to daytime frequency and Nocturia, there were significant increase in Group 2, compared with Group 1 8.90 ± 2.8 versus 7.16 ± 3.11, respectively, and 3.1 ± 1.2 versus 1.92 ± 1.12, respectively (p < 0.05).

Discussion

As the definitions of LUTS and OAB are closely intertwined, it would be logical to expect that both men and women would be offered similar symptom. Recently, the EPIC study was conducted in (Canada, Germany, Italy, Sweden and UK) it is a population-based cross sectional survey of adults 18 years of age or older of >19 000 participants [4]. Nearly 65% recorded at least one LUTS. The prevalence of storage symptoms (men, 51.3%; women, 59.2%) was more than that for voiding (men, 25.7%; women, 19.5%) and postmicturition (men, 16.9%; women, 14.2%) symptoms combined. Generally, prevalence of OAB was 11.8% and rates were parallel in men and women, increasing with age for both sexes, signifying that male LUTS cannot be refereed absolutely to the prostate

In another analysis of the EPIC study, Irwin et al. [14] reported that men with OAB symptoms recorded more LUTS and increase severity of symptoms than the general population.

Multiple pathological conditions, such as, arterial atherosclerosis and/or diabetes lead to bladder dysfunction are mainly or partially affected by ischemia/reperfusion injury. A study using a rat atherosclerosis model reported that chronic bladder ischemia increased the levels of oxidative stress markers and proinflammatory cytokines [15].

Additionally, Ponholzer et al. [7] reported that the IPSS increased significantly in men and women with two or more risk factors, signifying the effective role of atherosclerosis in the development of LUTS in men and women.

In the current study we investigate the impact of arterial obstructive conditions on lower urinary tract function by using FVC and UFM. The ultrasound examination of carotid artery was performed to diagnose atherosclerosis. Then using this parameter to estimate the effect of atherosclerosis on both voiding and storage function. We classified the patients into two groups according to the presence of atherosclerosis or not. There were no statistical significant differences in the patients’ age, prostate volume, IPSS, Voiding symptom scores and storage symptom score between the two groups. These findings were in agreement with the finding reported by Takahashi et al. [16]. Regarding, the voiding parameters, we observed significant decrease in Qmax and significant increase in PVR in atherosclerosis patients than that in non-atherosclerosis group. Although Takahashi et al. [16] reported significant decrease in Qmax atherosclerosis patients; he could not find significant difference in PVR between the atherosclerosis patients and the control group.

Regarding, the storage parameters, we observed significant increase in daytime frequency and nocturia and significant decrease in daytime voided urine in atherosclerosis patients. And our results were in agreement with Takahashi N et al. [16], although he found no significant difference in nocturia between the two groups.

Although, we did not find any significant difference in IPSS between the two groups, our results were in disagreement with the finding of Ponholzer et al. [7]. We can explain the discrepancy between the others’ studies and the current study to the difference in the number and characteristic of the patients and inaccuracy of IPSS recording.

According to cholesterol and lipids profile, there were statistical increases in Triglycerides and decrease in HDL cholesterol in blood serum in atherosclerosis patients than that in control group; these results are supported by Kawamoto et al. [17]. The results obtained by the current study show that atherosclerosis play a significant role in the impairments of both voiding and storage function irrelevant to the age.

There are multiple explanations to clarify the possible mechanism by which arterial occlusive disease impair the lower urinary function. Presently, it is considered that bladder dysfunction following pelvic vascular disease may in Part be caused by ischemia/reperfusion injury. During bladder emptying, the increased intra-wall tension results in blood vessel compression, decreased blood flow and tissue hypoxia. This occurs in normal bladders; yet, this phenomenon of ischemia–hypoxia is significantly exaggerated in patient with atherosclerosis [10,18].

Further study reported that arterial insufficiency results in denervation in the bladder through ischemia, hypoxia and oxidative stress [19]. This denervation leads to detrusor muscle hypersensitivity to acetylcholine and further antagonists [20] signifying that, denervation supersensitivity might be the beginning for detrusor overactivity following ischemia and hypoxia as well as bladder outlet obstruction. Additionally, the efferent neuron denervation may proceed to deteriorated detrusor contraction, leading to voiding dysfunction [21].

Conclusion

The present study revealed definitive correlation between the atherosclerosis and the lower urinary tract dysfunction. Arterial occlusive disease has an impact in the impairments of both voiding and storage function through ischemia, hypoxia and oxidative stress in the bladder. Further investigations are required to understand precisely the association of atherosclerosis to the progress of lower urinary tract dysfunction.

Our recommendations are that, treatment of cardiovascular risk factors, such as hypertension and hyperlipidemia, may contribute to the prevention of LUTS.

Declaration of interest

The author reports no conflicts of interest. The author alone is responsible for the content and writing of this article.

Acknowledgment

Special thanks to all my colleagues in the radiology department, for their technical radiological assistance and support.