Cynthia J. Girman

The prevalence of Prostatism: A Population-Based Survey of Urinary Symptoms

To establish the age-specific prevalence of urinary symptoms among a community-based cohort of men, a randomly selected sample of men were screened and invited to participate in a longitudinal survey of urinary symptoms. The population of Olmsted County, Minnesota, as enumerated by the Rochester Epidemiology Project, formed the sampling base for this study. Men between 40 and 79 years old with no history of prostate or other urological surgery, and who also were free of conditions associated with neurogenic bladder were invited to participate. A previously validated questionnaire was completed by the subject. Urine flow measures, current medications and family histories of urinary disease were also obtained. Nonresponse corrected scores for a composite of obstructive symptoms showed moderate to severe symptomatology among 13% of the men 40 to 49 years old and 28% of those older than 70 years. Prostatism is a highly prevalent symptom complex among unselected men in the community. The specific urinary symptoms of nocturia, weak stream, restarting, urgency and sensation of incomplete emptying are strongly age-related and, therefore, may be predictive of a prostatic disease process.

Natural History of Prostatism: Risk Factors for Acute Urinary Retention

PURPOSE We determined the occurrence of and risk factors for acute urinary retention in the community setting. MATERIALS AND METHODS A cohort of 2,115 men 40 to 79 years old was randomly selected from an enumeration of the Olmsted County, Minnesota population (55% response rate). Participants completed a previously validated baseline questionnaire that assessed symptom severity, and voided into a portable urometer to measure peak urinary flow rates. A 25% random subsample underwent transrectal sonographic imaging of the prostate to determine prostate volume. Followup was performed through a retrospective review of community medical records to determine the occurrence of acute urinary retention in the subsequent 4 years. RESULTS During the 8,344 person-years of followup 57 men had a first episode of acute urinary retention (incidence 6.8/1,000 person-years, 95% confidence interval [CI] 5.2, 8.9). Among men with no to mild symptoms (American Urological Association symptom index score 7 or less) the incidence of acute urinary retention increased from 2.6/1,000 person-years among men 40 to 49 years old to 9.3/1,000 person-years among men 70 to 79 years old. By contrast, rates increased from 3.0/1,000 person-years for men 40 to 49 years old to 34.7/1,000 person-years among men 70 to 79 years old among men with moderate to severe symptoms (American Urological Association symptom index score greater than 7). Men with depressed peak urinary flow rate (less than 12 ml. per second) were at 4 times the risk of acute urinary retention compared with men with urinary flow rates greater than 12 ml. per second (95% CI 2.3, 6.6). Men with an enlarged prostate (greater than 30 ml.) experienced a 3-fold increase in risk (95% CI 1.0, 9.0, p = 0.04). CONCLUSIONS Lower urinary tract symptoms, depressed peak urinary flow rates, enlarged prostates and older age are associated with an increased risk of acute urinary retention in community dwelling men. These findings may help to identify men at increased risk of acute urinary retention in whom closer evaluation may be warranted.

Metabolic Syndrome and 10-Year Cardiovascular Disease Risk in the Hoorn Study

Background—Different definitions of the metabolic syndrome have been proposed. Their value in a clinical setting to assess cardiovascular disease (CVD) risk is still unclear. We compared the definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP), World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), and American College of Endocrinology (ACE) with respect to the prevalence of the metabolic syndrome and the association with 10-year risk of fatal and nonfatal CVD. Methods and Results—The Hoorn Study is a population-based cohort study. The present study population comprised 615 men and 749 women aged 50 to 75 years and without diabetes or a history of CVD at baseline in 1989 to 1990. The prevalence of the metabolic syndrome at baseline ranged from 17% to 32%. The NCEP definition was associated with about a 2-fold increase in age-adjusted risk of fatal CVD in men and nonfatal CVD in women. For the WHO, EGIR, and ACE definitions, these hazard ratios were slightly lower. Risk increased with the number of risk factors. Elevated insulin levels were more prevalent in subjects with multiple risk factors, but metabolic syndrome definitions including elevated insulin level were not more strongly associated with risk. Conclusions—The metabolic syndrome, however defined, is associated with an approximate 2-fold increased risk of incident cardiovascular morbidity and mortality in a European population. In clinical practice, a more informative assessment can be obtained by taking into account the number of individual risk factors.

Non–High-Density Lipoprotein Cholesterol and Apolipoprotein B in the Prediction of Coronary Heart Disease in Men

BACKGROUND Apolipoprotein B (apoB) plasma levels reflect the concentration of proatherogenic lipoproteins very low-density lipoprotein and low-density lipoprotein (LDL), whereas non-high-density lipoprotein cholesterol (non-HDL-C) levels reflect the concentration of cholesterol transported by these particles. METHODS AND RESULTS The aim of our study was to compare apoB, non-HDL-C, LDL cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD) in a nested case-control study among 18 225 participants in the Health Professionals Follow-up Study. Among men who were free of diagnosed cardiovascular disease at the time of blood collection, 266 had nonfatal myocardial infarction or fatal CHD during 6 years of follow-up. Through the use of risk set sampling, control subjects were selected at a 2:1 ratio and matched with regard to age, date of blood collection, and smoking status. After adjustment for matching factors, the relative risk of CHD in the highest quintile compared with the lowest quintile was 2.76 (95% confidence interval [CI], 1.66 to 4.58) for non-HDL-C, 3.01 (95% CI, 1.81 to 5.00) for apoB, 1.81 (95% CI, 1.12 to 2.93) for LDL-C, 0.31 (95% CI, 0.18 to 0.52) for HDL-C, 2.41 (95% CI, 1.43 to 4.07) for triglycerides (all P trend <0.001), and 1.42 (95% CI, 0.86 to 2.32, P trend =0.19) for lipoprotein(a). When non-HDL-C and LDL-C were mutually adjusted, only non-HDL-C was predictive of CHD. When non-HDL-C and apoB were mutually adjusted, only apoB was predictive; the relative risk was 4.18 (95% CI, 1.30 to 13.49; P trend =0.02) for apoB compared with 0.70 (95% CI, 0.21 to 2.27; P trend =0.72) for non-HDL-C. Triglycerides added significant information to non-HDL-C but not to apoB for CHD risk prediction. CONCLUSIONS Although non-HDL-C and apoB were both strong predictors of CHD in this male cohort, more so than LDL-C, the findings support the concept that the plasma concentration of atherogenic lipoprotein particles measured by apoB is more predictive in development of CHD than the cholesterol carried by these particles, measured by non-HDL-C.

Insulin-like Growth Factor I, Insulin-like Growth Factor Binding Protein 3, and Urologic Measures of Benign Prostatic Hyperplasia

Laboratory studies suggest that insulin-like growth factor I (IGF-I) promotes prostatic growth. The authors evaluated the association between benign prostatic hyperplasia and IGF-I and its binding protein IGFBP-3 in community-dwelling men to determine whether this laboratory finding is manifest at the population level. Participants (n = 471) were Olmsted County, Minnesota, Caucasian males aged 40-79 years in 1990. Urologic measures were assessed from the International Prostate Symptom Score, peak urinary flow rates, prostate volume, and serum prostate-specific antigen (PSA), and serum IGF-I and IGFBP-3 levels were measured. After adjustment for age, the relative odds (odds ratios) of an abnormal urologic measure in men with high versus low serum IGF-I levels were 0.98 (95% confidence interval (CI): 0.66, 1.45) for a symptom score of >7, 1.14 (95% CI: 0.72, 1.80) for a peak urinary flow rate of <12 ml/second, 1.11 (95% CI: 0.72, 1.72) for a prostate volume of >30 ml, and 0.71 (95% CI: 0.46, 1.09) for a PSA level of >1.4 ng/ml. A low IGFBP-3 level was associated with an enlarged prostate (odds ratio = 1.72, 95% CI: 1.05, 2.82), after simultaneous adjustment for IGF-I and age, but not with other urologic measures. These data do not provide evidence for an association between benign prostatic hyperplasia and serum IGF-I.

Health-related quality of life associated with lower urinary tract symptoms in four countries

OBJECTIVES To describe health-related quality of life (HRQL) associated with lower urinary tract symptoms (LUTS) assessed by validated questionnaires in four countries. METHODS More than 6000 men, recruited by using community- or population-based sampling in four countries, completed questionnaires soliciting information about urinary symptom frequency, bother, degree of interference with daily activities, and other measures of HRQL. RESULTS In all countries, disease-specific HRQL worsened with increasing age. Adjusting for age, most disease-specific HRQL measures were significantly worse with increasing symptom severity. The correlation between symptoms and HRQL was strongest in countries with higher prevalence of symptoms, such as Japan or the United States, and less pronounced in countries with lower prevalence (France, Scotland), possibly reflecting the lower variability in scores. CONCLUSIONS HRQL measures are worse in older men, and increased urinary symptom severity is associated with worse disease-specific HRQL in all countries, despite potential cross-cultural differences in disease prevalence, medication use, perceptions, or willingness to report symptoms or worse HRQL. This cross-cultural consistency suggests that an assessment of symptom bother or interference with daily activities may be useful in patient evaluation.

Natural history of benign prostatic hyperplasia.

Studies in varied settings have provided estimates of the prevalence of surrogate markers of benign prostatic hyperplasia (BPH). In population-based studies, the prevalence of moderate-to-severe lower urinary tract symptoms and depressed peak urinary flow rates increases across successively older age groups. Prostatic volume follows a similar pattern. Unlike clinic-based studies in which correlations are almost nonexistent, the population-based studies demonstrate a modest correlation among lower urinary tract symptoms, peak urinary flow rates, and prostatic volume. These cross-sectional observations extend to serum prostate-specific antigen levels and postvoid residual urine volumes. Data collected during the longitudinal follow-up study of men participating in the Olmsted County Study of Urinary Symptoms and Health Status Among Men provide a more detailed description of the natural history of changes in these surrogate markers of BPH. They also provide insights into their relation with each other and with long-term outcomes of BPH, such as acute urinary retention and treatment of BPH. These data demonstrate the progressive nature of BPH and are useful for the design and interpretation of clinical trials. Furthermore, they suggest that observational studies of etiology and prognosis should take advantage of the spectrum of disease reflected by the full range of values of these quantitative traits, rather than an arbitrary dichotomized outcome.

NATURAL HISTORY OF PROSTATISM: RELATIONSHIP AMONG SYMPTOMS, PROSTATE VOLUME AND PEAK URINARY FLOW RATE

We describe relationships among symptoms, prostate volume and peak urinary flow rate in an age stratified, community based random sample of white men 40 to 79 years old with no prior prostate surgery, prostate cancer or other conditions known to interfere with voiding. Symptoms were assessed with an instrument comparable to the American Urological Association symptom index. Prostate volume was estimated by transrectal ultrasonography and peak urinary flow rate was measured by a portable device. Subject age was significantly associated with symptom score but accounted for only 3% of its variation, while prostate volume and peak urinary flow rate explained only an additional 10% of the symptom variability. The odds (95% confidence interval) of moderate to severe symptoms increased with age from 1.9 (1.1 to 3.1), 2.9 (1.7 to 5.0) and 3.4 (1.8 to 6.1) for men 50 to 59, 60 to 69 and 70 to 79 years old, respectively, relative to men 40 to 49 years old. Adjusting for age, the odds of moderate to severe symptoms were 3.5 times greater for men with prostatic enlargement (more than 50 ml.) than for men with smaller prostates, while the odds were similarly increased (2.4-fold) for men not achieving a peak urinary flow rate of 10 ml. per second. Estimated odds changed little when other cutoff points were considered for peak urinary flow rate (15 ml. per second) or prostate volume (40 ml.). These results, based on randomly selected white men, suggest a somewhat stronger, albeit modest, relationship among symptoms, prostate size and urinary flow rate than previously reported in clinic based studies. The strength of these relationships is comparable to that found with other diseases.

Natural history of prostatism: longitudinal changes in voiding symptoms in community dwelling men.

PURPOSE We report the results of 3 contacts during 42 months of The Olmsted County Study of Urinary Symptoms and Health Status Among Men, a longitudinal cohort study of men 40 to 79 years old that was initiated in 1990 to describe changes in lower urinary tract symptom severity. MATERIALS AND METHODS At baseline and followup, men completed questionnaires that elicited urinary symptom severity with questions nearly identical to those of the American Urological Association symptom index: RESULTS Overall, there was an average increase in American Urological Association symptom index of approximately 0.18 (95% confidence interval 0.13 to 0.24) points per year of followup. The average annual symptom score slope and variability in slope increased with patient age at baseline from a mean of 0.05 +/- 1.06 (standard deviation) per year among men in the forties to 0.44 +/- 1.35 per year for men in the sixties, and decreased to 0.14 +/- 1.42 per year for men in the seventies. The age-related changes in symptom severity mirror previous estimates of prostatic growth from autopsy prevalence studies. CONCLUSIONS These results demonstrate a slow but measurable progression in urinary symptom severity among community dwelling men for 42 months of followup.

Measures of Insulin Resistance Add Incremental Value to the Clinical Diagnosis of Metabolic Syndrome in Association With Coronary Atherosclerosis

Background—Whether measures of insulin resistance provide incremental information regarding atherosclerotic cardiovascular disease beyond current National Cholesterol Education Program (NCEP) Adult Treatment Panel III metabolic syndrome (MetSyn) criteria or inflammatory markers is uncertain. Methods and Results—We examined the association of insulin resistance and MetSyn with coronary artery calcification (CAC) in 840 asymptomatic nondiabetic subjects. Both NCEP and World Health Organization–defined MetSyn were associated (ordinal regression odds ratio [OR] and 95% confidence intervals for NCEP-defined MetSyn) with CAC after controlling for age, non-MetSyn risk factors, and plasma CRP levels (OR, 1.93 [1.43 to 2.60], P<0.001) and after further controlling for homeostasis model assessment index (HOMA) (OR, 1.56 [1.14 to 2.15], P=0.006). Conversely, HOMA was significantly associated with CAC after adjusting for age, non-MetSyn risk factors, and CRP levels (OR, 1.62 [1.31 to 2.01], P<0.001) and after further adjusting for NCEP-defined MetSyn (OR, 1.45 [1.16 to 1.82], P=0.007). Addition of HOMA to the NCEP MetSyn significantly improved the association with CAC, but addition of CRP data to MetSyn or HOMA did not. Conclusions—Both MetSyn and HOMA index were associated with coronary atherosclerosis independent of established risk factors, including CRP. These findings support the use of biomarkers of insulin resistance in addition to NCEP MetSyn criteria in assessing cardiovascular disease risk.