Association of Lower Urinary Tract Symptoms and the Metabolic Syndrome: Results From the Boston Area Community Health Survey
Article Outline
Purpose
In this study we investigated the relationship between lower urinary tract symptoms as defined by the American Urological Association symptom index and the metabolic syndrome, and determined the relationship between individual symptoms comprising the American Urological Association symptom index and the metabolic syndrome.
Materials and Methods
The Boston Area Community Health Survey used a 2-stage cluster design to recruit a random sample of 2,301 men 30 to 79 years old. Analyses were conducted on 1,899 men who provided blood samples. Urological symptoms comprising the American Urological Association symptom index were included in the analysis. The metabolic syndrome was defined using a modification of the Adult Treatment Panel III guidelines. The association between lower urinary tract symptoms and the metabolic syndrome was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models.
Results
Increased odds of the metabolic syndrome were observed in men with mild to severe symptoms (American Urological Association symptom index 2 to 35) compared to those with an American Urological Association symptom index score of 0 or 1 (multivariate OR 1.68, 95% CI 1.21–2.35). A statistically significant association was observed between the metabolic syndrome and a voiding symptom score of 5 or greater (multivariate adjusted OR 1.73, 95% CI 1.06–2.80) but not for a storage symptom score of 4 or greater (multivariate adjusted OR 0.94, 95% CI 0.66–1.33). Increased odds of the metabolic syndrome were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were observed primarily in younger men (younger than 60 years) and were null in older men (60 years old or older).
Conclusions
The observed association between urological symptoms and the metabolic syndrome provides further evidence of common underlying factors between lower urinary tract symptoms and chronic conditions outside the urinary tract.
Key Words: metabolic syndrome X, urinary tract, signs and symptoms, epidemiology
Abbreviations and Acronyms: ATP III, Adult Treatment Panel III, AUASI, American Urological Association symptom index, BACH, Boston Area Community Health, BMI, body mass index, BPH, benign prostatic hyperplasia, CES-D, Center for Epidemiological Studies–Depression scale, HDL, high-density lipoprotein, LUTS, lower urinary tract symptoms, MetS, the metabolic syndrome, NHANES III, Third National Health and Nutrition Examination Survey, SES, socioeconomic status
Increasing evidence from clinical and epidemiological studies showing associations between lower urinary tract symptoms and major chronic illnesses such as heart disease and diabetes as well as related lifestyle factors, have motivated interest in the contribution of factors outside the urinary tract to urological symptoms—the so-called beyond the bladder hypothesis.1, 2, 3, 4 However, few studies have investigated the possible association of LUTS with the metabolic syndrome, a constellation of cardiovascular risk factors thought to be linked by insulin resistance.
Associations between LUTS or BPH and anthropometric measures and obesity have been reported previously,5, 6, 7, 8 although findings are inconsistent.9, 10 LUTS have also been associated with components of MetS (hypertension2, 8 and fasting blood glucose7), and associated conditions (erectile dysfunction11) and lifestyle factors (physical activity,10, 12, 13, 14 alcohol consumption,13, 14 smoking13). An enlarged prostate is diagnosed more often in patients with type 2 diabetes and has been associated with components of MetS.6, 7, 15, 16 Data from NHANES III show a relationship between markers of MetS and LUTS defined as having 3 of 4 urinary symptoms (nocturia, incomplete bladder emptying, weak stream and hesitancy).4 However, this study was restricted to men 60 years old or older and included only 4 of the 7 urological symptoms comprising the AUASI.
Using data from the Boston Area Community Health Survey we examined the relative risk of men having 3 or more components of MetS as a function of the presence and severity of LUTS. Specific objectives of this analysis were to investigate the association between LUTS as defined by the AUASI and MetS, and to determine the relationship between individual symptoms comprising the AUASI and MetS.
Methods
Overall Design
The BACH survey is a population based epidemiological survey of a broad range of urological symptoms and risk factors in a randomly selected sample. Detailed methods have been described elsewhere.17 The BACH survey used a 2-stage stratified cluster sampling design to recruit approximately equal numbers of subjects according to age, gender and race/ethnicity (black, Hispanic and white). The BACH sample was recruited from April 2002 through June 2005. Interviews were completed with 63.3% of eligible subjects, resulting in a total sample of 2,301 men and 3,202 women after written informed consent was obtained. Analyses were conducted on 1,899 men who provided blood samples. All protocols and informed consent procedures were approved by the New England Research Institutes institutional review board.
Data Collection
Data were obtained during a 2-hour in-person interview conducted by a trained (bilingual) phlebotomist/interviewer in the subject's home. A random, not necessarily fasting venous blood sample (20 ml) was obtained, and height, weight, hip and waist circumference were measured. Self-reported information on medical history, major comorbidities, lifestyle and psychosocial factors as well as on symptoms of urological conditions was also collected. Two blood pressure measurements were obtained 2 minutes apart and were averaged. Medication use in the last month was collected using a combination of drug inventory and self-report with a prompt by indication.
Lower Urinary Tract Symptoms
LUTS were assessed using the AUASI, a clinically validated measure of urological symptoms with a reliable Spanish version.18, 19 The AUASI was used as a continuous variable and categorized into 2 groups as none or mild symptoms (AUASI less than 8) vs moderate or severe symptoms (AUASI 8 or greater). As an increase in the prevalence of MetS was observed with mild LUTS (AUASI 2 to 7), the AUASI was also categorized as 0 to 1, 2 to 7 and 8 to 35. Symptoms were further categorized as voiding (incomplete emptying, weak stream, intermittency, straining) and storage (frequency, urgency, nocturia) symptoms. Voiding and storage symptom scores were dichotomized as 5 or greater vs less than 5 for voiding and 4 or greater vs less than 4 for storage.2 Individual symptoms were first categorized as none (I do not have the symptom), mild (rarely/a few times) and severe (fairly often/usually/almost always), then into 2 groups as severe vs none/mild. Nocturia, assessed as the number of times having to get up at night after falling asleep to urinate, was first categorized as 0, 1, 2 or greater, then dichotomized as 2 or greater vs 0 or 1. Bother associated with urological symptoms was assessed by a validated quality of life questionnaire for BPH.20 A bother score was obtained by summing the score from 7 questions (scores for answers to each of questions ranged from 0 [none of the time] to 4 [all of the time] on the interference of urinary symptoms with various activities).
Metabolic Syndrome Definition
The metabolic syndrome was defined according to the ATP III guidelines.21 Available BACH data permit close adherence to the ATP III guidelines with the exception that available blood samples were usually nonfasting, impacting analyses of triglycerides and fasting glucose. In this analysis MetS was defined using a previously published modification of the ATP III guidelines as the presence of 3 or more of the 5 characteristics of 1) waist circumference greater than 102 cm; 2) systolic blood pressure 130 mm Hg or greater or diastolic blood pressure 85 mm Hg or greater, or antihypertensive medication use; 3) HDL cholesterol less than 40 mg/dl or lipid medication use; 4) self-reported type 2 diabetes or increased blood sugar or diabetes medication use; 5) triglycerides greater than 150 mg/dl.22
Covariates
Physical activity was measured using the Physical Activity Scale for the Elderly and was categorized as low (less than 100), medium (100 to 250) and high (greater than 250).23 Alcohol consumption was defined as alcoholic drinks consumed per day of 0, less than 1, 1 to 2.9, or 3 or more. Never smokers were defined as having smoked less than 100 cigarettes in their lifetime and pack-years of smoking were calculated by multiplying the number of packs smoked daily by the number of years smoked. Pack-years were categorized as less than 10, 10 to 19 and 20 or more. The socioeconomic status index was calculated using a combination of education and household income.24 SES was categorized as low (lower 25% of the distribution of the SES index), middle (middle 50% of the distribution) and high (upper 25% of the distribution).
Statistical Analysis
Odds ratios and 95% CIs were estimated using logistic regression methods to investigate the magnitude of the association between LUTS and MetS, and to adjust for potential confounders. A multiple imputation technique was used to obtain plausible variables for missing data.25 The proportions of participants with missing data were 0.6% for the AUASI, 0.7% for self-reported type 2 diabetes or increased blood sugar, 0.5% for waist circumference, 1.1% for lifestyle variables (physical activity, alcohol consumption, pack-years of smoking) and 5.4% for the SES index. Overall 7.5% participants had missing data on at least 1 of these variables. Twenty-five multiple imputations were performed separately by gender and race/ethnicity using all relevant variables. Observations were weighted inversely proportional to the probability of selection so that results would be generalizable to the city of Boston. Weights were post-stratified to the Boston population according to the 2000 Census. Analyses were conducted using SAS® version 9.1 and SUDAAN® version 9.0.1.
Results
Overall prevalence of MetS was 29.0%, comparable to the rates of 29.3% and 30.6% in adults 20 years or older from NHANES III and NHANES 1999–2000, respectively (table 1).26 The overall prevalence of moderate/severe LUTS (AUASI 8 or greater) was 19.3% and age specific rates were comparable to previously reported rates.27 The prevalence of MetS and LUTS did not differ by race/ethnicity (data not shown). A trend in increasing prevalence of MetS with increasing AUASI scores was observed (see figure). The prevalence of MetS was lowest for men reporting no symptoms or 1 symptom rarely at approximately 20%, and increased with mild LUTS (AUASI 2 to 7) to approximately 40% with no further increase with moderate to severe LUTS (AUASI 8 to 35).
Table 1. Descriptive characteristics of the analysis sample of 1,899 men who provided blood samples
| Observed No. (weighted %) | |
|---|---|
| Age: | |
 30–39 | 512 (37.2) |
| 40–49 | 554 (25.8) |
| 50–59 | 436 (17.8) |
| 60–69 | 260 (12.2) |
| 70–79 | 137 (7.0) |
| Race/ethnicity: | |
| White | 710 (61.9) |
| Black | 538 (25.1) |
| Hispanic | 651 (13.0) |
| SES: | |
| Low | 785 (23.9) |
| Middle | 787 (48.9) |
| High | 327 (27.2) |
| BMI (kg/m2): | |
| Less than 25.0 | 495 (26.8) |
| 25.0–29.9 | 740 (39.5) |
| 30 or Greater | 665 (33.7) |
| Physical activity: | |
| Low (less than 100) | 534 (25.5) |
| Medium (100–250) | 900 (48.2) |
| High (greater than 250) | 465 (26.3) |
| Alcohol consumption (drinks/day): | |
| None | 637 (28.8) |
| Less than 1 | 694 (40.2) |
| 1–2.9 | 362 (24.4) |
| 3 or More | 206 (9.2) |
| Smoking pack-yrs: | |
| Never | 815 (45.6) |
| Less than 10 | 517 (26.5) |
| 10–19 | 218 (11.5) |
| 20+ | 349 (16.5) |
| LUTS medication use | 49 (1.96) |
| AUASI 8 or greater | 368 (19.3) |
| Voiding score 5 or greater⁎ | 238 (12.8) |
| Storage score 4 or greater⁎ | 553 (28.9) |
| Diabetes/increased blood sugar/diabetes medication use | 284 (11.5) |
| Hypertension | 1,004 (46.8) |
| HDL less than 40 mg/dl or lipid medication use | 777 (39.8) |
| Triglycerides greater than 150 mg/dl | 868 (42.0) |
| Waist greater than 102 cm | 623 (33.4) |
| MetS | 613 (29.0) |
Prevalence of MetS increases with increasing AUASI score in mild symptoms range (AUASI 2 to 7), and stabilizes with moderate (AUASI 8 to 19) and severe (AUASI 20 to 35) symptoms. Overall trend test p = 0.003.
Similarly the association between AUASI and MetS was observed when comparing mild and moderate/severe symptoms to those with an AUASI score of 0 or 1 (age adjusted OR 1.83, 95% CI 1.29–2.60) (table 2). This association was slightly attenuated on multivariate analyses but remained statistically significant (multivariate OR 1.68, 95% CI 1.21–2.35). A statistically significant association was observed between MetS and voiding score (multivariate OR 1.73, 95% CI 1.06–2.80) but not with a storage score of 4 or greater (multivariate OR 0.94, 95% CI 0.66–1.33). Similar results were observed using the AUASI, voiding and storage scores as continuous variables (data not shown).
Table 2. Association of the metabolic syndrome (dependent variable) and LUTS (independent variable) assessed using the AUASI, and voiding (obstructive) and storage (irritative) scores
| Age Adjusted | OR (95% CI) | Multivariate Adjusted | OR (95% CI)⁎ | |
|---|---|---|---|---|
| AUASI: | ||||
| Less than 8 | 1.00 | 1.00 | ||
| 8 or Greater | 1.28 (0.84,1.95) | 1.14 (0.73,1.78) | ||
| 0–1 | 1.00 | 1.00 | 1.00 | 1.00 |
| 2–7 | 1.83 (1.23,2.72) | 1.83 (1.29,2.60)† | 1.72 (1.10,2.52) | 1.68 (1.21,2.35)† |
| 8 or Greater | 1.85 (1.19,2.86) | 1.59 (1.02,2.48) | ||
| Voiding score:† | ||||
| Less than 5 | 1.00 | 1.00 | ||
| 5 or Greater | 1.82 (1.11,3.01) | 1.73 (1.06,2.80) | ||
| Storage score:‡ | ||||
| Less than 4 | 1.00 | 1.00 | ||
| 4 or Greater | 1.35 (0.96,1.91) | 0.94 (0.66,1.33) | ||
| Bother score: | ||||
| Continuous | 1.06 (1.01,1.12) | 1.05 (0.99,1.11) | ||
| 0 | 1.00 | 1.00 | ||
| 1–8 | 0.86 (0.55,1.36) | 0.84 (0.52,1.34) | ||
| 9 or Greater | 2.95 (1.34,6.59) | 2.39 (1.01,5.67) |
⁎Adjusted for age, race, SES, physical activity, alcohol consumption, pack-year of smoking, LUTS medications. |
†OR for AUASI categories 2 to 7 and 8 or greater combined. |
Table 3 presents the association of individual symptoms and MetS. MetS was associated with mild/severe incomplete emptying (multivariate OR 1.58, 95% CI 1.03–2.44), intermittency (multivariate OR 1.57, 95% CI 1.06–2.30) and nocturia (multivariate OR 1.69, 95% CI 1.21–2.36). Increased odds of MetS were observed for men reporting severe urgency (age adjusted OR 1.92, 95% CI 1.14–2.34). However, the magnitude of this association was attenuated and was statistically nonsignificant on multivariate analyses. No association was observed between MetS and weak stream, straining or frequency.
Table 3. Association of the metabolic syndrome with individual urological symptoms comprising the AUASI
| Age Adjusted | OR (95% CI) | Multivariate Adjusted | OR (95% CI)⁎ | |
|---|---|---|---|---|
| Incomplete emptying: | ||||
| None/mild | 1.00 | 1.00 | ||
| Severe | 1.26 (0.37,1.91) | 0.94 (0.66,1.33) | ||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.51 (0.98,2.33) | 1.49 (0.94,2.37)† | 1.69 (1.11,2.58) | 1.58 (1.03,2.44)† |
| Severe | 1.43 (0.41,4.97) | 1.18 (0.38,3.70) | ||
| Intermittency: | ||||
| None/mild | 1.00 | 1.00 | ||
| Severe | 1.63 (0.83,3.20) | 1.47 (0.73,2.97) | ||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.60 (0.98,2.60) | 1.64 (1.10,2.45)† | 1.55 (0.95,2.52) | 1.57 (1.06,2.30)† |
| Severe | 1.79 (0.92,3.49) | 1.62 (0.82,3.21) | ||
| Weak stream: | ||||
| None/mild | 1.00 | 1.00 | ||
| Severe | 0.80 (0.45,1.41) | 0.74 (0.40,1.38) | ||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.19 (0.82,1.71) | 1.07 (0.76,1.50)† | 1.15 (0.77,0.77) | 1.03 (0.70,1.51)† |
| Severe | 0.82 (0.46,1.47) | 0.76 (0.40,1.44) | ||
| Straining: | ||||
| None/mild | 1.00 | 1.00 | ||
| Severe | 1.82 (0.45,7.82) | 1.58 (0.33,7.51) | ||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.30 (0.77,2.17) | 1.42 (0.81,2.48)† | 1.20 (0.69,2.07) | 1.29 (0.72,2.31)† |
| Severe | 1.88 (0.44,3.10) | 1.60 (0.34,7.76) | ||
| Frequency: | ||||
| None/mild | 1.00 | 1.00 | ||
| Severe | 0.76 (0.48,1.21) | 0.76 (0.44,1.17) | ||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 0.93 (0.64,1.34) | 0.86 (0.61,1.20)† | 0.91 (0.60,1.38) | 0.82 (0.56,1.20)† |
| Severe | 0.74 (0.45,1.20) | 0.69 (0.40,1.17) | ||
| Urgency: | ||||
| None/mild | 1.00 | 1.00 | ||
| Severe | 1.92 (1.14,2.34) | 1.63 (0.93,2.85) | ||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.28 (0.76,2.16) | 1.45 (0.95,2.21)† | 1.24 (0.71,2.16) | 1.35 (0.86,2.13)† |
| Severe | 2.04 (1.20,3.47) | 1.72 (0.97,2.03) | ||
| Nocturia: | ||||
| 0–1 | 1.00 | 1.00 | ||
| 2 or More | 1.63 (1.13,2.34) | 1.39 (0.96,1.99) | ||
| 0 | 1.00 | 1.00 | 1.00 | 1.00 |
| 1 | 1.70 (1.14,2.53) | 1.88 (1.37,2.58)† | 1.62 (1.07,2.44) | 1.69 (1.21,2.36)† |
| 2 or More | 2.19 (1.52,3.14) | 1.82 (1.26,2.64) |
⁎Adjusted for age, race, SES, physical activity, alcohol consumption, pack-year of smoking, LUTS medications. |
†OR for mild and severe categories combined. |
Table 4 presents the association of urological symptoms and individual components of MetS. Statistically significant associations between urological symptoms and type 2 diabetes and/or increased blood sugar were observed. Associations with other components were generally weak or null except the association of nocturia with increased odds of hypertension (adjusted OR 2.00, 95% CI 1.27–3.14) and increased triglycerides (adjusted OR 1.64, 95% CI 1.07–2.51), and mild LUTS (AUASI 2 to 7) and mild incomplete emptying with waist circumference greater than 102 cm. Previous analyses of BACH data have shown that the association of urological symptoms and measures of adiposity, including BMI and waist circumference, follow a U-shaped distribution in men, with a higher prevalence of urological symptoms with low or high BMI and waist circumference.28
Table 4. Association of LUTS with components of the metabolic syndrome
| OR (95% CI)⁎ | |||||
|---|---|---|---|---|---|
| Type 2 Diabetes/Increased Blood Sugar/Diabetes Medication Use | Hypertension/Antihypertensive Medication Use | HDL Less Than 40 mg/dl/Lipid Medication Use | Triglycerides Greater Than 150 mg/dl | Waist Larger Than 102 cm | |
| AUASI: | |||||
| 0–1 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| 2–7 | 1.95 (1.22,3.12) | 1.28 (0.87,1.88) | 1.38 (0.93,2.06) | 1.39 (0.99,1.95) | 1.44 (1.01,2.07) |
| 8–35 | 2.87 (1.56,5.31) | 1.15 (0.73,1.82) | 1.25 (0.79,1.99) | 1.04 (0.65,1.66) | 1.07 (0.66,1.73) |
| Voiding score: | |||||
| Less than 5 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| 5 or Greater | 1.93 (1.17,3.18) | 0.71 (0.46,1.09) | 1.44 (0.85,2.44) | 0.82 (0.5,1.35) | 1.39 (0.86,2.25) |
| Storage score: | |||||
| Less than 4 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| 4 or Greater | 1.58 (0.95,2.64) | 1.04 (0.74,1.47) | 0.86 (0.61,1.22) | 0.8 (0.57,1.13) | 0.75 (0.53,1.05) |
| Incomplete emptying: | |||||
| None | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.81 (1.04,3.15) | 1.04 (0.70,1.53) | 1.25 (0.85,1.84) | 0.98 (0.68,1.41) | 1.70 (1.17,2.47) |
| Severe | 0.90 (0.40,2.01) | 1.28 (0.37,4.40) | 1.02 (0.39,2.68) | 0.66 (0.21,2.06) | 1.48 (0.58,3.75) |
| Intermittency: | |||||
| None | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 2.77 (1.51,5.08) | 0.96 (0.63,1.46) | 1.32 (0.85,2.07) | 1.27 (0.84,1.94) | 1.14 (0.73,1.79) |
| Severe | 2.06 (0.87,4.86) | 1.05 (0.51,2.17) | 1.30 (0.69,2.44) | 0.65 (0.35,1.21) | 1.43 (0.75,2.75) |
| Weak stream: | |||||
| None | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.72 (1.04,2.82) | 0.82 (0.55,1.23) | 1.06 (0.68,1.66) | 0.90 (0.59,1.38) | 1.03 (0.64,1.67) |
| Severe | 1.25 (0.62,2.53) | 0.53 (0.30,0.94) | 0.73 (0.36,1.47) | 0.54 (0.27,1.05) | 0.65 (0.34,1.24) |
| Straining: | |||||
| None | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.95 (0.89,4.25) | 1.18 (0.67,2.09) | 1.02 (0.61,1.68) | 0.89 (0.52,1.51) | 1.50 (0.93,2.42) |
| Severe | 1.61 (0.71,3.64) | 0.74 (0.34,1.61) | 1.66 (0.39,7.07) | 0.57 (0.17,1.97) | 1.20 (0.34,4.28) |
| Frequency: | |||||
| None | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.89 (1.19,3.01) | 0.85 (0.58,1.22) | 1.14 (0.78,1.67) | 1.00 (0.71,1.43) | 0.68 (0.45,1.01) |
| Severe | 1.73 (0.89,3.37) | 0.93 (0.59,1.45) | 0.63 (0.39,1.00) | 0.66 (0.41,1.06) | 0.67 (0.41,1.08) |
| Urgency: | |||||
| None | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.60 (0.73,3.48) | 0.82 (0.51,1.33) | 1.11 (0.69,1.78) | 1.02 (0.64,1.62) | 1.09 (0.66,1.79) |
| Severe | 2.78 (1.48,5.23) | 1.23 (0.72,2.07) | 1.00 (0.56,1.77) | 0.84 (0.49,1.44) | 1.52 (0.87,2.63) |
| Nocturia: | |||||
| 0 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| 1 | 1.67 (0.82,3.39) | 1.24 (0.86,1.79) | 1.31 (0.92,1.87) | 1.46 (1.01,2.13) | 1.33 (0.90,1.96) |
| 2 or More | 2.62 (1.4,4.92) | 2.00 (1.27,3.14) | 1.40 (0.93,2.09) | 1.64 (1.07,2.51) | 1.34 (0.90,1.98) |
⁎Multivariate, adjusted for age, race, SES, physical activity, alcohol consumption, pack-year of smoking, LUTS medications. |
Analyses were stratified by age (younger than 60, or 60 years old or older) to determine whether the association between LUTS and MetS was different in younger compared to older men (table 5). Although interaction terms between LUTS and age were statistically nonsignificant, an overall trend was seen toward stronger associations with younger men (younger than 60 years) while most of the associations observed were null among older men (60 years old or older). This effect was most notable for the overall AUASI and MetS association, as well as some individual symptoms such as incomplete emptying, intermittency and nocturia. Few differences were observed in the patterns of association between LUTS and individual components of MetS in younger compared to older men (data not shown).
Table 5. Association of the metabolic syndrome and LUTS stratified by age
| Adjusted OR (95% CI)⁎ | ||||
|---|---|---|---|---|
| Younger Than 60 Yrs (1,502) | 60 Yrs or Older (397) | |||
| AUASI: | ||||
| 0–1 | 1.00 | 1.00 | 1.00 | 1.00 |
| 2–7 | 1.92 (1.29,2.86) | 1.99 (1.39,2.86)† | 1.14 (0.55,2.38) | 1.04 (0.51,2.10)† |
| 8 or Greater | 2.21 (1.28,3.82) | 0.92 (0.40,2.13) | ||
| Voiding score: | ||||
| Less than 5 | 1.00 | 1.00 | ||
| 5 or Greater | 1.86 (0.96,3.58) | 1.73 (0.87,3.44) | ||
| Storage score: | ||||
| Less than 4 | 1.00 | 1.00 | ||
| 4 or Greater | 1.15 (0.75,1.77) | 0.87 (0.44,1.71) | ||
| Bother score: | ||||
| Continuous | 1.09 (1.01,1.12) | 1.02 (0.98,1.07) | ||
| 0 | 1.00 | 1.00 | ||
| 1–8 | 0.89 (0.50,1.61) | 0.86 (0.43,1.71) | ||
| 9 or Greater | 5.04 (1.48,17.09) | 1.56 (0.72,3.51) | ||
| Incomplete emptying: | ||||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 2.16 (1.35,3.46) | 2.01 (1.26,3.20)† | 0.98 (0.50,1.91) | 0.92 (0.49,1.71)† |
| Severe | 1.48 (0.38,5.78) | 0.68 (0.22,2.14) | ||
| Intermittency: | ||||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 2.14 (1.20,3.79) | 1.98 (1.22,3.20)† | 0.89 (0.45,1.77) | 0.98 (0.53,1.84)† |
| Severe | 1.54 (0.70,3.36) | 1.25 (0.43,3.66) | ||
| Weak stream: | ||||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.45 (0.85,2.48) | 1.28 (0.79,2.08)† | 1.22 (0.61,2.44) | 1.03 (0.54,1.95)† |
| Severe | 0.88 (0.35,2.24) | 0.73 (0.28,1.91) | ||
| Straining: | ||||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.53 (0.75,3.13) | 1.65 (0.84,3.23)† | 0.94 (0.38,2.33) | 1.02 (0.45,2.33)† |
| Severe | 2.02 (0.41,9.98) | 1.63 (0.41,6.54) | ||
| Frequency: | ||||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.01 (0.66,1.55) | 0.94 (0.63,1.41)† | 0.74 (0.38,1.42) | 0.68 (0.37,1.24)† |
| Severe | 0.81 (0.43,1.55) | 0.61 (0.26,1.45) | ||
| Urgency: | ||||
| None | 1.00 | 1.00 | 1.00 | 1.00 |
| Mild | 1.40 (0.70,2.78) | 1.52 (0.85,2.70)† | 1.27 (0.62,2.61) | 1.53 (0.85,2.77)† |
| Severe | 2.04 (0.90,4.64) | 2.14 (0.96,4.74) | ||
| Nocturia: | ||||
| 0 | 1.00 | 1.00 | 1.00 | 1.00 |
| 1 | 2.15 (1.34,3.43) | 2.24 (1.48,3.39)† | 0.68 (0.33,1.39) | 0.80 (0.43,1.50)† |
| 2 or More | 2.43 (1.46,4.03) | 0.93 (0.46,1.88) | ||
⁎Adjusted for race/ethnicity, SES, physical activity, alcohol consumption, pack-years of smoking, LUTS medications. |
†OR for AUASI categories 2 to 7 and 8 or greater combined, or mild and severe categories combined. |
Discussion
Results from the BACH survey show that LUTS, assessed by the AUASI, are associated with MetS. Compared to men with no symptoms, increased odds of MetS in men with mild symptoms were comparable to the effect observed in men with moderate to severe symptoms. This pattern is also observed for individual symptoms associated with MetS, especially intermittency, incomplete emptying and nocturia. These associations were stronger in younger (younger than 60 years) compared to older men (60 years old or older). A statistically significant association was observed between MetS and voiding symptom score but not with storage symptom score.
Data from NHANES III have demonstrated a statistically significant association between MetS and LUTS (OR 1.82, 95% CI 1.11–2.94) in men 60 years old or older with LUTS defined as a report of 3 or 4 urological symptoms.4 While results from the present study show a similar association of LUTS assessed using the AUASI and MetS, the association in our study was primarily seen in younger men (younger than 60 years). Enlargement of the prostate has been proposed as a possible link between LUTS and MetS, as cross-sectional data suggest an association between BPH and increased body size, as well as components of MetS such as low HDL and increased fasting insulin or glucose.6, 7 In contrast, data from longitudinal epidemiological studies have shown no association between anthropometric measurements, hypertension or history of diabetes with the development of clinical BPH.9, 10 In contrast, a longitudinal study of 250 patients with LUTS reported a correlation between an increase in prostate size and diabetes, hypertension, obesity, high insulin and low HDL levels.15 Although an association of LUTS and MetS was observed in the present study, the temporal sequence between LUTS and MetS cannot be established from analyses of cross-sectional data.
Possible pathophysiological mechanisms to explain the relationship of voiding rather than storage symptoms with MetS include the influence of sustained hyperglycemia on the viability of parasympathetic neurons in the pelvic ganglion. Animal studies have shown that long-term increased serum glucose induces neuronal apoptosis that favors parasympathetic neuron loss compared to sympathetic.29 Such an unbalanced loss of autonomic neurons might induce an oversupply of sympathetic tone compared to parasympathic efferent activity resulting in increased bladder neck obstruction and reduced bladder power, which combined might produce an increase in obstructive symptoms as noted. Increased glucose levels are likely to be accompanied by hyperinsulinemia which results in an increase in insulin-like growth factor, a known prostatic mitogen, and induces a reduction in proapoptotic cascades in the prostate.30 These changes should culminate in increased prostate growth and an increase in voiding symptoms, as noted in this report. The emerging role of phosphodiesterase type 5 inhibitors for the treatment of LUTS has recently revealed that the nitric oxide synthase-nitric oxide/cyclic guanosine monophosphate pathway may influence voiding symptoms via nitrinergic supply to the prostate or bladder, or by bladder perfusion induced compliance changes.31, 32 Such influences are likely to be impaired in obese men with MetS. Alternative hypotheses include pelvic atherosclerosis leading to chronic ischemia of the bladder, penis and prostate, which may result in impairment of lower urinary tract function.33, 34
Although diabetes is the most common cause of peripheral neuropathy and is linked with several aspects of voiding dysfunction, even in overt diabetes the mechanism of voiding dysfunction in males is unknown. An emerging consensus of investigators suggests that diabetic linked bladder neuropathy is principally a sensory defect resulting in a delayed desire to void due to the absence of urgency.35 With time this putative delay in desire results in a large bladder capacity, decreased detrusor contractility, impaired outflow and increased post-void residual urine. An associated motor neuropathy, hypotonic bladder, has also been described. Despite these proposed mechanisms involuntary bladder contractions and detrusor hyperreflexia are major components of voiding complaints.36, 37
These findings have important diagnostic and management implications. Patients who present with components of metabolic dysfunction should be routinely queried with respect to urological function, particularly voiding symptoms such as intermittency, incomplete emptying and nocturia, as well as the degree of associated bother. Sexual dysfunction symptoms, particularly erectile dysfunction, are similarly reported by the majority of men with MetS and should be routinely evaluated. The role of lifestyle changes such as weight loss and increased physical activity in the management of urological symptoms in patients with MetS remains to be established. In addition to management of the components of metabolic dysfunction, first line medications (eg α-blockers, phosphodiesterase type 5 inhibitors) should be recommended when indicated for the management of voiding and sexual dysfunction symptoms in these patients.
Several potential study limitations should be noted. Fasting blood samples were not obtained, thus available data permit close approximation but not perfect adherence to the ATP III guidelines for the definition of MetS.15, 16 Despite this recognized limitation our approach has scientific merit because 1) the ATP III components have always been suggested guidelines rather than an immutable clinically validated definition; 2) there is continuing debate regarding which components of MetS should be included, removed or added; and 3) it is used as a concept for the purposes of epidemiological analysis rather than for clinical purposes. The benefits of using data from a large population based sample outweigh the recognized limitations associated with the measurement of some components of MetS. The BACH study was limited geographically to the Boston area. However, comparison of sociodemographic and health related variables from the BACH survey with other large regional (BRFSS [Boston Behavioral Risk Factor Surveillance System]) and national (National Health Interview Survey, BRFSS, NHANES) surveys has shown that BACH estimates are comparable in terms of health related variables. Strengths of the BACH study include a community based random sample across a wide age range (30 to 79 years old), inclusion of large numbers of minority participants representative of black and Hispanic populations, and collection of a broad number of covariates on sociodemographic, lifestyle and health factors that can be adjusted for in the analysis.
Conclusions
The results of this study demonstrate an association between urological symptoms and MetS. Increased odds of MetS were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were stronger in younger men (younger than 60 years) compared to older men (65 years old or older). Further research is needed to understand the common pathophysiology of LUTS and MetS, especially longitudinal studies to determine a temporal sequence and investigation of this association in women as a relationship between chronic illnesses and LUTS has been reported previously in men and women.1 Additional studies are needed to explore the treatment impact and correlation of comorbid conditions and symptoms associated with the individual components of MetS.
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Study received institutional review board approval.
Supported by Pfizer, Inc.
The BACH survey is supported by DK 56842 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.
PII: S0022-5347(09)00934-3
doi:10.1016/j.juro.2009.04.025
© 2009 American Urological Association. Published by Elsevier Inc. All rights reserved.