Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia

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Kaohsiung Journal of Medical Sciences (2015) xx, 1e5

Available online at www.sciencedirect.com

ScienceDirect journal homepage: http://www.kjms-online.com

ORIGINAL ARTICLE

Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia Mehmet Murat Baykam a, Binhan Kagan Aktas a,*, Suleyman Bulut a, Cuneyt Ozden a, Tagmac Deren b, Suleyman Tagci a, Cevdet Serkan Gokkaya a, Ali Memis a a b

Urology Clinic, Numune Training and Research Hospital, Ankara, Turkey Radiology Clinic, Numune Training and Research Hospital, Ankara, Turkey

Received 2 September 2014; accepted 5 December 2014

KEYWORDS Benign prostatic hyperplasia; Cardiovascular system; Doppler ultrasonography; Metabolic X syndrome; Regional blood flows

Abstract We evaluated the relationship between prostatic resistive index (RI) and cardiovascular system (CVS) risk factors in patients with benign prostatic hyperplasia. The study included 120 patients who were attending our outpatient clinic with lower urinary tract symptoms related to benign prostatic hyperplasia. The clinical, laboratory, anthropometric data, and CVS risk factors (hypertension, diabetes mellitus, metabolic syndrome, history of CVS events, and smoking) of the patients were evaluated regarding the association between prostate RI level by regression analyses. The prostatic RI levels of the patients were measured using power Doppler imaging. In univariate regression analysis, there were statistically significant relationships between prostatic RI levels and the patients’ age, International Prostate Symptom Score, hip circumference, fasting blood glucose, prostate specific antigen, triglycerides, highdensity lipoprotein cholesterol, low-density lipoprotein cholesterol, total prostate volume, uroflowmetric maximal flow rate, and all investigated CVS risk factors (p < 0.05). The prostatic RI levels were found to be associated with fasting blood glucose and total prostate volume, and also with CVS risk factors including only metabolic syndrome and cigarette smoking in the multivariate regression analysis. Our results showed that prostatic RI level is significantly related to metabolic syndrome and smoking among the investigated CVS risk factors. Copyright ª 2015, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.

Conflicts of interest: All authors declare no conflicts of interest. * Corresponding author. Numune Egitim ve Arastirma Hastanesi, Uroloji Klinigi, Ulku Mahallesi, Talatpasa Boulevard, Number 5, Ankara 06100, Turkey. E-mail address: [email protected] (B.K. Aktas). http://dx.doi.org/10.1016/j.kjms.2014.12.008 1607-551X/Copyright ª 2015, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.

Please cite this article in press as: Baykam MM, et al., Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia, Kaohsiung Journal of Medical Sciences (2015), http://dx.doi.org/10.1016/j.kjms.2014.12.008

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Introduction Benign prostatic hyperplasia (BPH) is histologically defined as a nonmalignant, unregulated overgrowth of the prostate gland. Secondary to an enlarged prostate, BPH may be clinically associated with lower urinary tract symptoms (LUTS) [1]. LUTS in the aging man is primarily caused by BPH. Up to 90% of men in their 70s have some LUTS suggestive of BPH (LUTS/BPH), and their health-related quality of life is impaired because of these discomfiting symptoms [2]. LUTS/ BPH may less commonly progress to serious morbidities including acute urinary retention, a need for surgery, urinary incontinence, or a recurrent urinary tract infection [3]. Age and genetics play important roles in the etiologies of BPH and LUTS. And, in addition to them, unhealthy diets, a sedentary lifestyle, inflammation, and some major cardiovascular system (CVS) risk factors including hypertension (HT), noninsulin-dependent diabetes mellitus (DM), obesity, smoking, dyslipidemia, and metabolic syndrome (MetS) were reported to be novel modifiable risk factors in the development of BPH in recent studies [4e8]. Transrectal ultrasonography is one of the classical methods used in the evaluation of BPH patients. The use of transrectal probes in color and power Doppler imaging (PDI) gives detailed information about intraprostatic vascularity [9]. It has been reported that the development of LUTS/ BPH causes an increase in both vascular resistance and prostatic resistive index (RI), and prostatic RI is correlated with the symptom score and urine flow rate in LUTS/BPH patients [10,11]. In this study, with an attempt to provide etiologic information and find new preventions, we evaluated the relationship between the prostatic RI levels and CVS risk factors in patients with LUTS/BPH.

Methods Patients A total of 120 consecutive BPH patients aged 50 years or older and exhibiting LUTS at our urology outpatient clinic in a tertiary care teaching hospital between January 2013 and March 2014 were prospectively included in this study. Patients with a history of prostatic malignancy, prostatic surgery, bladder neck or urethral stricture, and previous LUTS therapy, and those with neurologic diseases affecting the lower urinary tract were not included in the study. The patients were fully informed about the study design, and informed consent was obtained from all participating patients. Initially, a detailed medical history was taken from each patient. CVS risk factors including smoking status, presence of DM, HT, or a history of CVS events (coronary heart disease or myocardial infarction) were recorded. The urologic evaluation included a digital rectal examination, International Prostatic Symptom Score (IPSS), urinalysis, maximum flow rate (Qmax) on uroflowmetry, and postvoid residual urine volume. Anthropometric measurements including weight, height, hip circumference (HC), and waist circumference (WC) were taken for each patient by the same observer (S.T.), using the same methods and instruments for all the patients, and body mass index values were

M.M. Baykam et al. calculated by dividing weight in kilograms by height in meters squared. WC and HC were measured respectively by using a nonelastic constant tension tape at the midpoint of the lowest rib and iliac crest at the end of exhalation, and around the widest portion of the buttocks with the participant standing. Their blood pressure was measured using a Braun BP6200 Exactfit 5 Automatic Blood Pressure Monitor (Kaz Inc., Braun GmbH, Kronberg, Germany). The blood samples were drawn from the overnight-fasting participants, and the serum levels of fasting blood glucose (FBG), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and prostate-specific antigen (PSA) were recorded. The criteria proposed for the clinical diagnosis of MetS were provided by the report of the National Cholesterol Education Program’s Third Adult Treatment Panel III, any three of the five following factors: abdominal obesity (WC >102 cm), HT (blood pressure >130/85 mmHg or taking antihypertensive medication), hyperglycemia (FBG >110 mg/dL), hypertriglyceridemia (serum TG >150 mg/dL), and reduced levels of HDL-C (<40 mg/dL) [12].

Measurement of prostatic RIs The prostatic RIs were measured by a radiologist (T.D.) using PDI. The ultrasound examination consisted of a transrectal ultrasonography and PDI using a GE Logiq E9 (General Electric Healthcare Systems, Chalfont St Giles, UK) with a 9-MHz endocavitary probe while the patient was lying on top of an examination table in a left lateral decubitus position. The patients were asked to empty their urinary bladder to prevent intraprostatic vasculature from the compression. The total prostate volume (Vp) and transitional zone volumes (Vtz) were calculated using the ellipsoid formula, and then recorded. The blood flow from the three capsular arteries on the largest transverse section of the prostate was measured, and then a spectral waveform analyses was performed. When the pulsatile waveforms of a given Doppler spectrum became stable, the RIs [(maximum velocity minimum velocity)/maximum velocity] were measured from each of the three blood flow samples using the onboard software, and the mean value was calculated and then recorded.

Statistical analysis All statistical analyses were performed using SPSS, version 18 (SPSS Inc., Chicago, IL, USA). The descriptive statistics were presented as mean  SD, and statistical analyses were performed using Pearson’s correlation and linear regression tests. A p value < 0.05 was considered significant. Additionally, we conducted a post hoc power analysis with the G*Power 3.0.10 software program (Heinrich-Heine University, Du ¨sseldorf, Germany) to identify the power achieved [13].

Results The mean values of patient characteristics are shown in Table 1. Of the total 120 patients, 60 (50.0%) were hypertensive, 49 (40.8%) were diabetic, 58 (48.3%) had MetS, 55

Please cite this article in press as: Baykam MM, et al., Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia, Kaohsiung Journal of Medical Sciences (2015), http://dx.doi.org/10.1016/j.kjms.2014.12.008

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Vascular risk factors and resistive index Table 1

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Mean patient characteristics.

Variables Age (y) Height (cm) Weight (kg) BMI (kg/m2) WC (cm) HC (cm) FBG (mg/dL) TG (mg/dL) LDL-C (mg/dL) HDL-C (mg/dL) IPSS PSA (ng/mL) Vp (mL) Vtz (mL) Qmax (mL/sn) PVR urine volume (mL) PRI

Mean  SD 62.1 169.6 77.3 26.9 103.5 102.5 107.3 148.4 137.1 41.8 20.5 2.8 46.8 11.3 11.4 100.7 0.74

                

8.6 5.12 11.04 3.4 12.11 6.7 25.8 39.1 27.4 8.2 6.6 4.0 33.4 10.7 5.1 96.1 0.068

BMI Z body mass index; FBG Z fasting blood glucose; HC Z hip circumference; HDL-C Z high-density lipoprotein cholesterol; IPSS Z international Prostatic Symptom Score; LDL-C Z lowdensity lipoprotein cholesterol; PRI Z prostatic resistive index; PSA Z prostate-specific antigen; PVR Z postvoid residual; Qmax Z maximum flow rate on uroflowmetry; SD Z standard deviation; TG Z triglyceride; Vp Z total prostate volume; Vtz Z transitional zone volume; WC Z waist circumference.

(45.8%) had a history of CVS events, and 92 (76.7%) were smokers. There were 46 hypertensives (76.4%), 44 diabetics (89.8%), 44 patients with a history of CVS events (80.0%), and 47 patients with MetS (81.0%) who were identified as smokers. Prostatic RI levels were positively correlated with age, IPSS, PSA, FBG, TG, LDL-C, Vp, and Vtz, and negatively correlated with HC, HDL-C, and Qmax. Prostatic RI levels were also positively correlated with CVS risk factors including HT, DM, MetS, smoking, and history of CVS events (Table 2). In the univariate regression analysis, there were statistically significant relationships between the prostatic RI levels and age, IPSS, HC, FBG, PSA, TG, HDL-C, LDL-C, Vp and Vtz, Qmax, and all investigated CVS risk factors (Tables 3 and 4). However, in the multivariate regression analysis, the prostatic RI levels were found to be related to FBG, Vp, and the CVS risk factors including only MetS and smoking (Tables 3 and 4). The power of the present study to detect a medium effect size (0.3) was calculated to be 99.3%; critical t Z 1.98; df Z 118; noncentrality parameter d Z 3.44 at a significance level of 0.05 (two-tailed test) using correlation analysis.

Discussion The availability of power and color Dopplers on transrectal probes improved the diagnosis of BPH via the detection of intraprostatic vascularity [14]. PDI, the next generation of color Doppler imaging, is based on the detection of signal amplitude, which determines the density of red blood cells,

Table 2 Correlation among PRI, patient characteristics and CVS risk factors. Variables

PRI r

Age (y) Height (cm) Weight (kg) BMI (kg/m2) WC (cm) HC (cm) FBG (mg/dL) TG (mg/dL) LDL-C (mg/dL) HDL-C (mg/dL) IPSS PSA (ng/mL) Vp (mL) Vtz (mL) Qmax (mL/sn) PVR urine volume (mL) HT DM CVS events history MetS Smoking

0.408 0.166 0.095 0.019 0.130 0.248 0.512 0.221 0.427 0.309 0.453 0.466 0.528 0.397 0.399 0.084 0.553 0.627 0.579 0.620 0.286

p

R2

0.000 0.070 0.303 0.841 0.156 0.006 0.000 0.016 0.000 0.001 0.000 0.000 0.000 0.000 0.000 0.372 0.000 0.000 0.000 0.000 0.002

0.167 0.028 0.009 0.000 0.017 0.062 0.263 0.049 0.182 0.096 0.205 0.217 0.279 0.157 0.159 0.007 0.306 0.393 0.335 0.385 0.082

BMI Z body mass index; CVS Z cardiovascular system; DM Z diabetes mellitus; FBG Z fasting blood glucose; HC Z hip circumference; HDL-C Z high-density lipoprotein cholesterol; HT Z hypertension; IPSS Z international Prostatic Symptom Score; LDL-C Z low-density lipoprotein cholesterol; MetS Z metabolic syndrome; PRI Z prostatic resistive index; PSA Z prostate-specific antigen; PVR Z postvoid residual; Qmax Z maximum flow rate on uroflowmetry; TG Z triglyceride; Vp Z total prostate volume; Vtz Z transitional zone volume; WC Z waist circumference.

the independent flow rate, and direction [15]. The development of BPH was reported to increase vascular resistance and prostatic RI [16,17]. In the present study, prostatic RI was found to correlate positively with both Vp and IPSS, and negatively with Qmax, which is similar to previous studies [18,19]. It is not clear how prostatic RI increases in BPH, but it is considered that the growing hypertrophic prostate pushes the capsule outward and results in an increase of intraprostatic pressure and prostatic RI [20]. The decreases in both intraprostatic pressure and prostatic RI following transurethral prostatectomy in the patients with LUTS/BPH corroborate with this hypothesis [21]. The two well-known etiologic factors of LUTS/BPH are aging and testicular androgens [4]. However, in some studies, a relationship between the development of LUTS/ BPH and CVS risk factors such as HT, obesity, dyslipidemia, DM, and MetS has been reported [5e8]. Several studies have suggested that CVS risk factors may cause enlargement of the prostate by causing chronic prostatic ischemia [22,23]. Using cell culture models, Berger et al. [24] detected that prostatic stromal cells increase the secretion of growth factors in response to hypoxia. However, Takada et al. [25] reported that CVS risk factors that cause arteriosclerosis are not related to prostatic RI in patients with symptomatic

Please cite this article in press as: Baykam MM, et al., Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia, Kaohsiung Journal of Medical Sciences (2015), http://dx.doi.org/10.1016/j.kjms.2014.12.008

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M.M. Baykam et al. Table 3

Results of univariate and multivariate regression analysis of PRI according to patient characteristics.

Variables

Univariate Constant

Beta

Multivariate t

p

12.582 1.830 1.034 0.201 1.428 2.786 6.483 2.456 5.123 3.535 5.520 5.719 6.758 4.696 4.651 0.897

0.000 0.070 0.303 0.841 0.156 0.006 0.000 0.016 0.000 0.001 0.000 0.000 0.000 0.000 0.000 0.372

Beta Constant

Age (y) Height (cm) Weight (kg) BMI (kg/m2) WC (cm) HC (cm) FBG (mg/dL) TG (mg/dL) LDL-C (mg/dL) HDL-C (mg/dL) IPSS PSA (ng/mL) Vp (mL) Vtz (mL) Qmax (mL/sn) PVR urine volume (mL)

0.539 1.119 0.790 0.755 0.670 1.004 0.600 0.688 0.600 0.852 0.649 0.723 0.695 0.717 0.799 0.735

0.003 0.002 0.001 0.000 0.001 0.003 0.001 0.000 0.001 0.003 0.005 0.008 0.001 0.003 0.005 0.000

t

1.461 1.035 0.001 1.238 0.004 0.527 0.004 0.440 0.012 0.475 0.001 1.133 0.002 1.813 0.001 3.491 0.000 0.768 0.000 1.837 0.000 0.298 0.001 1.563 0.002 0.731 0.001 2.231 0.001 0.616 0.001 0.665 0.000 0.503 R Z 0.727 F Z 6.936 p Z 0.000 R2 Z 0.529 Adjusted R2 Z 0.452

p 0.303 0.219 0.599 0.661 0.636 0.260 0.073 0.001 0.444 0.069 0.766 0.121 0.466 0.028 0.539 0.507 0.616

BMI Z body mass index; FBG Z fasting blood glucose; HC Z hip circumference; HDL-C Z high-density lipoprotein cholesterol; IPSS Z international prostatic symptom score; LDL-C Z low-density lipoprotein cholesterol; PRI Z prostatic resistive index; PSA Z prostate-specific antigen; PVR Z postvoid residual; Qmax Z maximum flow rate on uroflowmetry; TG Z triglyceride; Vp Z total prostate volume; Vtz Z transitional zone volume; WC Z waist circumference.

prostate growth rate were higher in patients with MetS than in the control group. A significant relationship between MetS and prostatic RI in patients with BPH may be explained by an increased Vp in patients with MetS. The significant relationship between prostatic RI, MetS, and Vp found in patients with LUTS/BPH in our study also supports this theory. One might think that HT and DM rates of the present study seem higher than those in daily urologic practice. However, our data are consistent with previously published results that belong to a population of the same age group in our country [29]. Despite their high prevalence rates, HT and DM were not found to be associated with prostatic RI in our cohort.

BPH. However, this study did not include DM and MetS among CVS risk factors causing arteriosclerosis. Chen et al. [23] found a significant relationship between prostatic RI and the number of vascular risk factors including obesity, HT, DM, hyperlipidemia, and CVS events in patients with BPH, but this time, MetS was not counted as a CVS risk factor in the study. In the present study, the prostatic RI level was found to be significantly associated with only MetS and smoking among the CVS risk factors investigated in patients with LUTS/BPH, and indeed, 81% of our patients with MetS were smokers. A significant relationship between MetS and LUTS/ BPH has also been shown in a few other studies [6,26,27]. Hammarsten et al. [28] found that Vp and the annual

Table 4

Results of univariate and multivariate regression analysis of PRI according to CVS risk factors.

Variables

Univariate

Multivariate

Constant

Beta

t

p

0.708 0.710 0.709 0.705 0.710

0.075 0.086 0.079 0.084 0.046

7.215 8.743 7.710 8.589 3.245

0.000 0.000 0.000 0.000 0.002

Beta Constant

HT DM CVS events history MetS Smoking

t

0.685 60.794 0.017 0.945 0.018 1.056 0.028 1.757 0.035 1.935 0.024 2.026 R Z 0.717 F Z 16.962 p Z 0.000 R2 Z 0.515 Adjusted R2 Z 0.484

p 0.000 0.347 0.293 0.082 0.045 0.045

CVS Z cardiovascular system; DM Z diabetes mellitus; HT Z hypertension; MetS Z metabolic syndrome.

Please cite this article in press as: Baykam MM, et al., Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia, Kaohsiung Journal of Medical Sciences (2015), http://dx.doi.org/10.1016/j.kjms.2014.12.008

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Vascular risk factors and resistive index We should mention the limitations of our study: as in all observational studies, unmeasured confounders such as other nutritional or lifestyle factors might have potentially affected our results. The relatively small sample size and the lack of a control group are also limitations to our study. Therefore, controlled future studies with a large number of patients are needed to support our findings.

Conclusion Our results showed that among CVS risk factors, MetS and smoking were related to prostatic RI in patients with LUTS/ BPH. Chronic prostatic ischemia related to CVS risk factors might, therefore, play an important role in the pathogenesis of LUTS/BPH.

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Please cite this article in press as: Baykam MM, et al., Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia, Kaohsiung Journal of Medical Sciences (2015), http://dx.doi.org/10.1016/j.kjms.2014.12.008