Estrogen levels are higher across the menstrual cycle in African-American women compared with Caucasian women.

CONTEXT: Previous studies have suggested that estrogen levels may be higher in African-American women (AAW) compared with Caucasian women (CW), but none have systematically examined estrogen secretion across the menstrual cycle or in relation to other reproductive hormones. OBJECTIVE: The objective of the study was to compare estradiol (E2), progesterone (P), gonadotropins, androstenedione (a'dione), inhibins, and SHBG levels between AAW and CW across the menstrual cycle. DESIGN, SETTING, AND SUBJECTS: Daily blood samples were collected from regularly cycling AAW (n = 27) and CW (n = 27) for a full menstrual cycle, and serial ultrasounds were performed. MAIN OUTCOME MEASURES: Comparison of E2, P, LH, FSH, SHBG, inhibin A, inhibin B, and a'dione levels. RESULTS: AAW and CW were of similar age (27.2 ± 0.6 yr, mean ± sem) and body mass index (22.7 ± 0.4 kg/m(2)). All subjects grew a single dominant follicle and had comparable cycle (25-35 d) and follicular phase (11-24 d) lengths. E2 levels were significantly higher in AAW compared with CW (P = 0.02) with the most pronounced differences in the late follicular phase (225.2 ± 14.4 vs. 191.5 ± 10.2 pg/ml; P = 0.02), midluteal phase (211.9 ± 22.2 vs.150.8 ± 9.9, P < 0.001), and late luteal phase (144.4 ± 13.2 vs. 103.5 ± 8.5, P = 0.01). Although LH, FSH, inhibins A and B, P, a'dione, and SHBG were not different between the two groups, the a'dione to E2 ratio was lower in AAW (P < 0.001). CONCLUSIONS: Estradiol is higher in AAW compared with CW across the menstrual cycle. Higher estradiol in the face of similar androstenedione and FSH levels suggests enhanced aromatase activity in AAW. Such differences may contribute to racial disparities in bone mineral density, breast cancer, and uterine leiomyomas.

Effects of combined administration of ACE inhibitor and angiotensin II receptor antagonist are prevented by a high NaCl intake.

BACKGROUND: To prevent the action of angiotensin II by blockade with either an angiotensin converting enzyme inhibitor (ACE I) or an angiotensin receptor antagonist (ARA) is difficult due to the physiological compensations. Combined therapy with both drugs may enable complete blockade, and in rats in high doses this has produced a syndrome that results in death. OBJECTIVE: To determine the effect of combined blockade using losartan (10 mg/kg per day) and perindopril (6 mg/kg per day) on blood pressure, cardiac growth, renal function and behaviour, and to determine how this is influenced by different salt intakes in normotensive Sprague Dawley rats. METHODS: Rats were fed an 0.2 or 4% NaCl diet and received the above drugs intraperitoneally. Blood pressure was measured by telemetry. Cardiac weight was measured after 10 days of therapy. Renal function was assessed by plasma creatinine and electrolytes, plasma renin and angiotensinogen concentrations were measured. RESULTS: On 0.2% NaCl intake, combined blockade lowered blood pressure progressively; at day 7, rats on 0.2% NaCl developed a syndrome of listlessness and failure to eat which led to loss of weight and death. Cardiac size was dramatically reduced. Plasma creatinine was elevated to 50% above normal. There was a polyuria. The syndrome was reversed by adding NaCl to the drinking water or prevented in rats on a 4% NaCl intake. In rats on 0.2% NaCl plasma renin rose dramatically with medication and angiotensinogen became depleted. Haematocrit in all groups of rats did not differ. CONCLUSION: Combined blockade of the renin-angiotensin system can cause death in rats on a reduced NaCl intake. This was prevented by a high salt intake. The syndrome may result from depletion of angiotensinogen and the failure to synthesize sufficient angiotensin II that may be critical for normal cardiac growth and function and critical for survival.

ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension.

The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure (SBP) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy. Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits. Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each. The study was a balanced, randomized crossover design with five periods: placebo; angiotensin converting enzyme inhibitors; beta-blocking drugs; calcium-blocking drugs; and thiazide diuretics. Blood pressure (BP) was measured 24 to 26 h after the previous dose. A questionnaire for side effects was administered at each visit. Seventy-four patients entered the study. beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods. There were 9 of 66 patients on P, 9 of 46 on beta-blockers, 4 of 65 on calcium-blocking drugs, 4 of 65 on diuretic, and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects. Decreases in SBP compared to randomized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg. Blood pressure decrease correlated with placebo BP (P < .0005, r = 0.53 to 0.70). When corrected for placebo, target SBP (<140 mm Hg) was reached in between 6% to 15% of patients on monotherapy. Sequential monotherapy achieved target in 29%. Angiotensin converting enzyme inhibitors, calcium-blocking drugs, and diuretics had no more side effects than placebo. Patients on beta-blockers had more side effects and the well-being score was reduced. Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure. beta-Blockers were relatively ineffective, were frequently contraindicated, and had more side effects. Monotherapy achieved control in only a small number of patients. In elderly people with essential hypertension, therapy should be instituted with diuretics or calcium-blocking drugs, but combination therapy will usually be required to achieve goal.

Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril.

Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population. Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure (BP). The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake, whereas the angiotensin-converting enzyme (ACE) inhibitors' effects can be blunted by a high-sodium diet. This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril. Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril. The response was assessed by ambulatory BP measurement. Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine. The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril. Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin. It is postulated that the effect is due to inhibition of prostaglandin synthesis, which causes sodium retention. In patients taking amlodipine, the fall in plasma renin ameliorates the effect of sodium retention on BP. In patients taking enalapril, plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme. Thus, the full effect of sodium retention on BP is expressed. In patients treated with indomethacin, fewer patients may respond to ACE inhibitors. However, the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs, which, if a person is treated by an ACE inhibitor causes BP to go out of control. In such patients amlodipine would appear to be a preferred choice to enalapril.

Pubovaginal sling: 4-YEAR outcome analysis and quality of life assessment.

PURPOSE: Stress urinary incontinence is a common disease with a devastating impact on patient quality of life. Needle suspension procedures, which produce disappointing long-term results for type II stress incontinence, are being replaced by pubovaginal slings which previously were reserved solely for the treatment of type III stress incontinence. We report the long-term outcomes of pubovaginal slings for the treatment of types II and III stress urinary incontinence, and assess its quality of life impact. MATERIALS AND METHODS: From January 1993 until December 1996, 247 females 10 to 84 years old (mean age 54.5) with type II (54%) or III (46%) stress urinary incontinence diagnosed by fluoroscopic urodynamics received a pubovaginal sling. Concomitant urge incontinence was present in 109 patients (44%). Quality of life was assessed with the Urogenital Distress Inventory short form. RESULTS: At a mean followup of 51 months (range 22 to 68) the continence rates were 88% overall, 91% for type II and 84% for type III. Preoperative urge incontinence resolved in 81 of 109 patients (74%), while de novo urge incontinence developed in 10 (7%). Intermittent urethral catheterization duration averaged 8.4 days, with 5 women undergoing urethrolysis for a hypersuspended urethra. Secondary procedures were required in 9 patients with type II and 5 with type III incontinence, and included transurethral collagen injections in 6 and repeat pubovaginal slings in 8. There was a 4% complication rate due to pelvic hematoma in 2 cases, incisional hernia in 2, deep venous thrombosis in 1 and pulmonary embolus in 1. Of the 247 patients 235 (95%) completed the quality of life questionnaire with 92% reporting a high degree of satisfaction with low (less than 20 of 100 points) symptom distress scores. CONCLUSIONS: Pubovaginal slings are effective and durable, and significantly improve quality of life in patients with types II and III stress urinary incontinence.

Cardiac hypertrophy depends upon sleep blood pressure: a study in rats.

OBJECTIVE: The objective of this study was to determine whether cardiac hypertrophy in hypertensive rats could be reduced and normalized by intermittent reduction of blood pressure, and to determine whether left ventricular hypertrophy was related to 24 h workload or peak blood pressure responses. METHODS: Hypertension was created by the application of a 0.20 mm clip to the left renal artery. Blood pressure response was monitored using a telemetry system (Data Science International). Blood pressure was reduced for varying periods of the day by giving different doses of captopril in the drinking water or by intra-peritoneal administration. Cardiac size was measured by weighing the ventricles and factoring by the body weight to obtain a cardiac index. RESULTS: Captopril 75 mg/kg per day and 25 mg/kg per day in the drinking water administered between 1800 and 2000 h lowered the 24 h blood pressure more than captopril 15 mg/kg per day or 5 mg/kg per day intra-peritoneally given at 0800 h. Captopril 75 mg/kg per day and captopril 15 mg/kg per day (intra-peritoneal) caused regression of cardiac hypertrophy whereas the other doses had no effect The best predictor of the cardiac hypertrophy response was the blood pressure between 0800 and 1200 h (i.e. the sleeping blood pressure). Twenty-four hour cardiac work did not correlate with the response. CONCLUSION: Cardiac hypertrophy can be reduced by intermittent treatment of elevated blood pressure. It is also caused by intermittent elevation of blood pressure. It appears that the crucial factor is when these alterations in blood pressure take place. An elevated blood pressure during the sleeping hours causes left ventricular hypertrophy, whereas a normal blood pressure during the sleeping hours allows reduction. It is suggested that acute wall stress is the signal to initiate the events that lead to cardiac hypertrophy but this only occurs if the hormonal milieu is appropriate.

Ethanol effects on cardiomyocyte contractility.

Little is known about the direct cardiac effects of socially common sub-intoxication levels of ethanol. Previous studies evaluating the responses of normal cardiomyocytes to short-term ethanol exposure have utilized ethanol concentrations equivalent to extreme intoxication or lethal levels in vivo. The purpose of the present study was to investigate the contractile responses of isolated rat ventricular cardiomyocytes during exposure to relatively low concentrations of ethanol in the range 0.05-0.5% (v/v) (8.6-86 mM) under physiological conditions (3 Hz stimulation; 36 degrees C; BSA vehicle). High-speed imaging techniques were used to study the kinetics of myocyte contraction, and shortening parameters were calculated for mechanistic evaluation. The concentration-response relationship was not linear and exhibited two plateau phases, suggesting at least two mechanisms of action of ethanol on cardiomyocyte contraction. At 0.05% (8.6 mM), ethanol treatment produced a 14.4% decrease in maximum myocyte shortening. The maximum rates of cell shortening and lengthening were similarly impaired, but there was no effect on contraction cycle timing at this low concentration. At 0.30% (51 mM), ethanol reduced maximum shortening by 40.2%, prolonged excitation-contraction coupling latency and abbreviated the contraction cycle time by 38%. The inotropic modulatory effect of ethanol was exaggerated in the absence of protein in the superfusion buffer. This is the first report which identifies ethanol at 0.05% (v/v) as a modulator of cardiac contractility. Kinetic analyses indicate that the mechanism of action involves disturbance of sarcoplasmic reticulum function, and this may contribute to arrhythmogenic vulnerability - especially in an in vivo context of heightened compensatory sympathetic drive.

Effects of aortic ligation on the renin angiotensin system in hydronephrotic mice.

A model of aortic ligation in mice with a hydronephrotic kidney (absence of macula densa) was used to determine the effects of aortic ligation on the renal renin-angiotensin system (RAS). Blood pressure increased from 83 +/- 2 to 133 +/- 8 mmHg within 7 days after aortic ligation (p < 0.01). Aortic ligation increased plasma renin (p < 0.01); renin (p < 0.05) and renin mRNA levels (p < 0.001) rose in the ischaemic kidney. In mice with a left hydronephrotic kidney without ischaemia, blood pressure did not change significantly. Plasma renin levels from the left renal vein were lower than from the contralateral vein, but renin (p < 0.01) and renin mRNA levels (p < 0.05) in the hydronephrotic kidney were higher than in the contralateral kidney. In mice with hydronephrosis that had an aortic ligature, blood pressure increased from 81 +/- 2 to 135 +/- 6 mmHg (p < 0.01). Plasma renin increased; renin and renin mRNA levels increased significantly in the ischaemic hydronephrotic kidney (p < 0.01), but not in the contralateral kidney. Thus, the presence of the macula densa is critical for renin release but not for renin gene expression. Aortic ligation results in a significant rise in blood pressure and the activity of the RAS. The mechanisms may involve a baroreceptor and/or an unknown factor.

Angiotensin blocking drugs and the heart beyond 2000.

Cardiac hypertrophy can be caused in different ways, and the effect of hypertrophy on prognosis depends on whether it is concentric or eccentric in nature. It is simplistic to ascribe hypertrophy purely to workload, and it is a complex interaction between workload, wall stress, and the local and humoral environment. In rats, acute elevation of BP occurring during the rats' sleep cycle causes cardiac hypertrophy, and reduction of BP in hypertensive rats during the sleep cycle causes reversal of left ventricular hypertrophy. This may be due to secretion of growth hormone and renin during sleep. Experimental evidence indicates that angiotensin II possibly formed and acting locally may be implicated in the genesis of cardiac hypertrophy; however, angiotensin II by itself causes relatively minor hypertrophy, but this becomes intensified if there is a high sodium intake and a high angiotensin II level. Blockade of the angiotensin system with angiotensin-converting enzyme inhibitors causes reversal of cardiac hypertrophy and similar results are achieved with AT1 receptor blocking drugs, suggesting that bradykinin may be of relatively minor importance. Clinically, the AT1 receptor blocking drugs have few side effects and appear to have similar beneficial effects to angiotensin-converting enzyme inhibitors, making them suitable to treat many people with hypertension.

Sodium, angiotensin II, blood pressure, and cardiac hypertrophy.

Blood pressure (BP) in rats was elevated intermittently by i.p. injections of angiotensin II (Ang II; 200 microg/kg), and the effect on cardiac index was determined. The BP response was assessed in selected rats by telemetry. Elevation of BP between 8:00 and 12:00 produced cardiac enlargement similar to that produced by continuous Ang II infusion, and the response correlated better with the acute BP elevation than with 24-hour cardiac work. A high-sodium diet also increased left-ventricular hypertrophy (LVH) without a major effect on BP. The addition of Ang II intensified this response. A low-sodium diet had no significant effect on BP or on cardiac size, but prevented the cardiac hypertrophy produced by Ang II without altering the BP response. These results suggest that acute BP elevation, probably working through increased wall tension, is a more potent stimulus for cardiac hypertrophy than 24-hour workload. The sodium intake of the rat plays an important role influencing the cardiac but not the BP response to Ang II. These results infer that it is important to avoid episodes of acute BP elevation.

The prevalence of obstructive sleep apnea in hypertensives.

This study was designed to measure the prevalence of obstructive sleep apnea in untreated and treated hypertensive patients by comparing them with normotensive subjects, taking into account the possible confounding variables body mass index, age, sex, and alcohol consumption. Subjects with no known sleep disorders were recruited, had full polysomnography, and had their blood pressure assessed with a 24-h ambulatory monitor. Subjects with a mean 24-h blood pressure greater than 140/90, and receiving no treatment for, or with no history of, hypertension were classified as untreated hypertensives; those receiving antihypertension medication were classified as treated hypertensives; those with a mean 24-h blood pressure less than 140/90 and no history of hypertension were classified as normotensives. Thirty-eight percent of the 34 untreated and 38% of the 34 treated hypertensives, and 4% of the 25 normotensives had apnea-hypopnea indexes greater than 5. Logistic regression analysis showed that body mass index (p = 0.001), age (p = 0.07), sex (p = 0.07), treated hypertension (p = 0.05), and untreated hypertension (p = 0.06) were associated with the presence of sleep apnea, but that alcohol consumption (p = 0.82) was not. It is concluded that there is a relationship between sleep apnea and hypertension that, although partially explained by the confounding variables body mass index, age, and sex, persists when these are allowed for.

Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: a randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events. The International Study Group.

The primary aim of this double-blind, parallel group trial was to compare incidence of newly occurring vasodilatory adverse events in elderly patients treated with recommended once-daily doses of felodipine extended release (ER) or amlodipine. A total of 535 patients over 65 years old with a sitting diastolic blood pressure of 90-115 mmHg and/or systolic blood pressure 160-220 mmHg, were recruited at 46 centres worldwide. Patients were randomised to felodipine ER 2.5 mg or amlodipine 5 mg. If blood pressure was > 160/90 mmHg after three or six weeks, felodipine ER was increased to 5 and 10 mg and amlodipine to 10 mg. After nine weeks, average doses of felodipine ER and amlodipine were 5.5 mg and 7.3 mg, respectively. Newly occurring vasodilatory adverse events were reported by 32% of felodipine ER patients and 43% of amlodipine patients (p = 0.007). Both treatments effectively reduced blood pressure 24 hours post-dose. Using a low starting dose and individual titration, felodipine ER achieves good control of blood pressure with few vasodilatory side-effects.

Comparison of serum prostate specific membrane antigen, prostate specific antigen, and free prostate specific antigen levels in radical prostatectomy patients.

BACKGROUND: Higher preoperative prostate specific antigen (PSA) levels are associated with higher pathologic stage and grade in patients undergoing radical prostatectomy (RP). In earlier studies, serum prostate specific membrane antigen (PSMA) elevations were associated with clinical progression and hormone-refractory carcinoma. The goal of this study was to evaluate the serum markers PSMA, free PSA (FPSA), free:total PSA ratio (F:TPSA), and total PSA (PSA) in men undergoing RP. METHODS: Serum was obtained from 63 patients undergoing RP for clinically localized (T1c, T2) prostate carcinoma. Serum PSA and FPSA were determined by Hybritech Tandem-E(R) and Tandem-R(R), respectively, and PSMA was determined by Western blot analysis. Serum values for these markers were compared with the pathologic stage, surgical margin status, Gleason sum, prostate size (as calculated via reconstruction and transrectal ultrasound), tumor size based on pathologic assessment of the whole mount, and World Health Organization (WHO) grade of the prostatectomy specimen. Markers were also compared against demographic information and the patients' age and race. RESULTS: There was a weak correlation between serum PSA and positive surgical margins, higher Gleason sum, and WHO grade (P < 0.05). Receiver operating characteristic curve (ROC) analysis comparing sensitivity and specificity of the markers to positive and negative margins as well as seminal vesicle invasion demonstrated PSA and FPSA predictive ability for seminal vesicle invasion. The area under the curve for PSA and FPSA in this case was 0.7318 and 0.7432, respectively. There was also a weak correlation between the FPSA level and margins, with a low ROC area under the curve of 0.6789. The FPSA cannot distinguish the more advanced stage of disease. There was no significant correlation between F:TPSA and PSMA with regard to the study variables in predicting organ confinement. High PSMA levels only correlated with higher stage and were maximal in pT4a classified disease. CONCLUSIONS: Higher PSA and FPSA levels are likely to be associated with more locally advanced disease. Total PSA was the best marker. However, the cutoff values necessary for significant accuracy between PSA and FPSA are not of clinical usefulness due to the lack of specificity and sensitivity of the markers at those cutoffs. F:TPSA and PSMA levels as currently measured are of limited value in discriminating more aggressive disease in patients with clinically localized CaP.

Second Australian National Blood Pressure Study (ANBP2). Australian Comparative Outcome Trial of ACE inhibitor- and diuretic-based treatment of hypertension in the elderly. Management Committee on behalf of the High Blood Pressure Research Council of Australia.

The Second Australian National Blood Pressure Study (ANBP2) is a comparative outcome trial being conducted in general practices throughout Australia of ACE inhibitor- and diuretic-based treatment in 6000 hypertensive patients aged 65-84 years. The study is using a prospective randomised open-label design with blinding of endpoint assessments. The primary objective is to determine whether there is any difference in total cardiovascular events (fatal and non-fatal) over a five year treatment period between the two treatment regimens. Eligible hypertensive patients (average sitting blood pressure at the 2nd and 3rd screening visits > 160 mm Hg systolic and/or > 90 mm Hg diastolic) may be either untreated or previously treated and should have no history of recent cardiovascular morbidity or serious intercurrent illness. Patients are randomised to one of the treatment arms with randomisation stratified for practice and for age. Following randomisation each patient's blood pressure is managed by his/her general practitioner according to guidelines relevant to each treatment arm. Over 700 patients have now been randomised with recruitment intended to be complete by the end of 1997.

Feasibility of conducting cardiovascular outcome research in Australian general practice: results from the ANBP2 pilot study. Australian National Blood Pressure Study.

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was > or = 160 mmHg systolic or > or = 90 mmHg diastolic if systolic BP was > or = 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82,000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP > or = 160/90 mmHg. Forty-seven per cent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.

Prospective use of free prostate-specific antigen to avoid repeat prostate biopsies in men with elevated total prostate-specific antigen.

OBJECTIVES: We prospectively evaluated whether free PSA improves the specificity of PSA and can be useful as a clinical guide to avoid repeat prostate biopsies in patients with persistent PSA elevations, normal digital rectal examinations, and previous negative prostate biopsies. METHODS: Sixty-seven men with persistent PSA elevations (median 9.5, range 4.1-24.8 ng/mL), normal digital rectal examinations and two or more prior sextant biopsies (mean 2.8) had serum collected for measurement of total and free PSA. All patients were rebiopsied to determine the receiver operating characteristics of total PSA versus percent free PSA for prostate cancer detection. RESULTS: The study biopsy identified 11 prostate cancer cases. The median percent free PSA was significantly higher at 18.0% among men without prostate cancer compared to 6.7% in men with prostate cancer (P < 0.00005). When sensitivity was plotted against 1-specificity, the area under the receiver operating characteristic curve for percent free PSA was 0.93, compared to 0.69 for free PSA density, 0.66 for PSA density, and 0.51 for PSA. In patients with elevated total PSA levels, normal digital rectal examinations and two prior negative sets of sextant prostate biopsies, a cutoff of 10% free PSA would maintain sensitivity at 91% with a corresponding specificity of 86%. CONCLUSIONS: Selective measurement of percent free PSA can significantly improve the specificity of prostate cancer screening with PSA. A low percent free PSA (< 10%) appears to be a powerful predictor of prostate cancer even after two negative prostate biopsies.

Age-specific reference ranges for serum prostate-specific antigen in black men.

BACKGROUND: The detection of prostate cancer by screening for prostate-specific antigen (PSA) in serum is improved when age-specific reference ranges are used, but these ranges have been derived from white populations. We determined the distribution of PSA and age-specific reference ranges in black men both with and without prostate cancer. METHODS: From January 1991 through May 1995, we measured serum PSA in 3475 men with no clinical evidence of prostate cancer (1802 white and 1673 black) and 1783 men with prostate cancer (1372 white and 411 black). We studied the data as a function of age and race to determine the usefulness of measuring PSA in diagnosing prostate cancer. RESULTS: Serum PSA concentrations in black men (geometric mean in controls, 1.48 ng per milliliter; in patients, 7.46) were significantly higher than those in white men (geometric mean in controls, 1.33 ng per milliliter; in patients, 6.28). The values in the controls correlated directly with age. The area under the receiver-operating-characteristic curve was 0.91 for blacks and 0.94 for whites. If traditional age-specific reference ranges were used in screening black men, with the test specificity kept at 95 percent, 41 percent of cases of prostate cancer would be missed. For the test to have 95 percent sensitivity among black men, the following normal reference ranges should be used: for men in their 40s, 0 to 2.0 ng of PSA per milliliter (test specificity, 93 percent); for men in their 50s, 0 to 4.0 ng per milliliter (specificity, 88 percent); for men in their 60s, 0 to 4.5 ng per milliliter (specificity, 81 percent); and for men in their 70s, 0 to 5.5 ng per milliliter (specificity, 78 percent). CONCLUSIONS: Serum PSA concentrations can be used to discriminate between men with prostate cancer and those without it among both blacks and whites. Over 40 percent of cases of prostate cancer in black men would not be detected by tests using traditional age-specific reference ranges, which maintain specificity at 95 percent. In this high-risk population, the alternative approach--maintaining sensitivity at 95 percent--may be used with acceptable decrements in specificity.