Gender-based cardiometabolic risk evaluation in minority and non-minority men grading the evidence of non-traditional determinants of cardiovascular risk.

Evaluation of cardiometabolic risk has become vital in primary prevention of adverse vascular events (coronary artery disease, heart attack, stroke or congestive heart failure), particularly in younger middle-aged men (40-60 years old). To discern the prevalence of events in these men, clinicians often stratify cardiovascular risk and treat according to traditional Framingham risk criteria. Yet it is evident that the traditional Framingham risk assigned to intermediate- and low-risk men will miss several of these individuals deemed at high 'cardiometabolic risk', also known as residual cardiovascular risk. This review will elaborate the definition of cardiometabolic risk and apply the use of surrogate markers for cardiovascular risk stratification in men in addition to the traditional Framingham-based markers. It will utilise both gender non-specific and gender-specific determinants of cardiometabolic risk. Lastly, it will examine minority men's health and racial differences in these determinants of cardiovascular risk. This analysis includes an electronic literature search utilising PubMed, EMBASE and MEDLINE databases to clarify the level of evidence for the stepwise utility of novel biomarkers for cardiometabolic risk in the male patient. This manuscript generates discussion of the utility of markers of cardiometabolic risk stratification. The following questions are summarised: (i) Are there non-traditional tests that might define this risk better than traditional markers? (ii) Will treatment based on this risk assessment augment present risk stratification and lower cardiovascular risk? (iii) What is known regarding racial differences surrounding cardiometabolic risk assessment? Traditional risk factors including Framingham Risk Score underestimate the overall 10 year and lifetime risk for the intermediate-risk younger middle-aged men<60 years of age. This fact is especially true in the minority population. We have graded the evidence of non-gender specific and gender-specific markers of cardiometabolic risk, thereby, allowing greater clarification of risk in this population. The pragmatic use of these novel markers of cardiometabolic risk may help stratify those individuals at greater lifetime risk than that noted by the Framingham Risk Score.

Erectile dysfunction and testosterone screening with prostate specific antigen screening at age 40: are these three gender specific determinants additive for overall men's heath and do they improve traditional non-gender specific determinants to lessen cardiovascular risk and all-cause mortality?

AIMS: Assess support for a recommendation to add screening for both erectile dysfunction (ED) and hypogonadism to the initial medical evaluation of young-to-middle aged (≥ 40 years of age) men in light of recent guidelines suggesting prostate-specific antigen screening occur at that age. METHODS: A search of literature published from 1998 to 2009 was performed. Search terms included: ED combined with coronary artery disease (CAD), metabolic syndrome and hypogonadism, hypogonadism and ED, hypogonadism, ED and mortality. Articles were evaluated according to the Center of Evidence-Based Medicine. RESULTS: Both retrospective and prospective evaluations have demonstrated a strong relationship between ED, established cardiovascular risk factors, CAD and the potential occurrence of cardiovascular events. Low testosterone levels are associated with ED. Low serum total testosterone is an independent risk factor for both metabolic syndrome and type 2 diabetes and all-cause mortality. CONCLUSION: Traditionally, ED and testosterone levels have been considered mainly, if not exclusively, in the context of sexual health. The results briefly summarised herein and other recent reviews suggest that ED and hypogonadism are signals of future all-cause mortality and overall health status and thus move these evaluations into the broader arena of public health. Screening for ED and hypogonadism provide 'gender-specific determinants' to assess general metabolic and cardiovascular health risks in men. It is the opinion of the authors that this screening be performed in addition to the well-established non-gender-specific screening tests of lipids, blood pressure, obesity and serum glucose.

Biology and natural history of prostate cancer and the role of chemoprevention.

Androgens not only play an important role in the development and function of the prostate but they are also intimately involved in the development and progression of prostate cancer (PCa). Within the prostate, testosterone is converted to the more potent androgen dihydrotestosterone (DHT) via the action of 5α-reductase enzymes. DHT is the primary prostatic androgen and promotes the growth and survival of normal, hyperplastic and malignant prostate tissues. Throughout the different stages of PCa [prostatic intraepithelial neoplasia (PIN), localised, recurrent, and metastatic] there is an increase in expression of 5α-reductase enzymes, particularly in localised high-grade carcinoma. Specifically inhibiting 5α-reductase may reduce the production of DHT in the prostate while maintaining other endogenous hormone levels. Clinical studies have shown significant PCa risk reduction by blocking this pathway with 5α-reductase inhibitors (5ARIs). However, this comes at a risk, albeit low, with sexual side effects, gynaecomastia and cardiac failure. In addition, one study has shown a slight, but significant, risk of high-grade PCa. The currently available evidence does not support the routine use of 5α-reductase inhibitors to prevent PCa in the general population. It could, however, be considered as an individual option for high-risk or concerned patients with appropriate education from the prescribing provider.

STEP: simplified treatment of the enlarged prostate.

We propose a simple and practical approach to the identification, evaluation and treatment of lower urinary tract symptoms (LUTS) resulting from an enlarging and obstructive prostate. The proposed Simplified Treatment for Enlarged Prostate (STEP) plan is a logical guide to patient management by the primary care provider (PCP). Symptoms of enlarged prostate (EP) are common and may frequently progress into a condition with profound adverse effects on quality of life. Despite the high prevalence, EP is underdiagnosed and undertreated. This situation may result from patient- and provider-related issues. Assessment of symptoms of EP should be initiated with a discussion of LUTS. Evaluation includes a focused history, physical examination and selected laboratory tests. Certain factors put the symptomatic patient at risk for disease progression; however, not all factors can be readily evaluated in the PCP setting. The serum prostate-specific antigen (PSA) level acts both as an indicator of prostatic size and a screening tool for prostatic cancer, and thereby provides an important tool for PCPs. The STEP plan is a logical guide to patient management. Step 1, watchful waiting, is appropriate in patients with symptoms that are not bothersome. If symptoms cause bother, the initiation of an alpha-blocker (AB) in step 2, provides relatively rapid symptom improvement. Patients with bothersome symptoms and a PSA > or = 1.5 ng/ml are at risk for progression and consideration should be given to combination treatment with an AB and a 5alpha-reductase inhibitor (step 3). Patients with refractory symptoms should be referred to a urologist (step 4). Identification, evaluation and management of EP are within the domain of the primary care setting. The STEP approach provides a simple and practical framework for PCPs to manage most men with symptoms of EP.

Do baseline estrogen and testosterone affect lower urinary tract symptoms (LUTS) prior to or after pharmacologic treatment with tadalafil?

Little is known about how total testosterone and estradiol-17ß influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged ≥18 years randomized to tadalafil 5 mg once-daily or placebo who had ≥6 month history of LUTS and an International Prostate Symptom Score (IPSS)≥13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17ß, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17ß and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (ΔIPSS), ΔIPSS-V, and ΔIPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17ß was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17ß versus those with higher baseline estradiol-17ß. Lower baseline estradiol-17ß was significantly associated with modestly improved ΔIPSS-V (p = 0.04) and Δtotal IPSS (p = 0.05) but not with ΔIPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict ΔIPSS. Men with lower baseline estradiol-17ß levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17ß levels when responsiveness was measured using total IPSS and IPSS-V.

Tortuosity as an index of the age and diameter increase of coronary collateral vessels in patients after acute myocardial infarction.

A possible correlation among increase in diameter, lengthening or tortuosity and age of bypassed obstruction was investigated in coronary arterial collateral vessels. In 35 autopsy patients with a myocardial infarct of known age, as determined from clinical history and pathologic demonstration of an infarct of consistent age in the distribution of an obstructed vessel, 140 collateral vessels were identified in postmortem arteriograms and measurements made of their diameter and tortuosity. Multivariable regression analyses showed that collateral diameter and tortuosity increase with greater time after the infarction. It is suggested that identification of tortuosity in a coronary vessel may provide an indication that it functions as a collateral channel and of the degree of its dilatation and the time it has been a collateral channel. The lengthening that produces tortuosity probably arises from the same relaxation of medial tension that induces dilatation as a result of increased blood flow.

Stopwatch-assessed duration of erection: a new measure of the efficacy of erectile dysfunction treatments.

Results are reported from the first two adequate trials of the PDE-5 inhibitor vardenafil using a stopwatch to precisely measure erection duration in men with ED. Two randomized, multicenter, double-blind, placebo-controlled trials were conducted: a crossover 4-week treatment in men with ED (ENDURANCE) and a parallel group, 12-week treatment in men with ED and dyslipidemia (the dyslipidemia study). Stopwatch-assessed duration of erection leading to successful intercourse measured by Sexual Encounter Profile question-3 (SEP-3) was the primary end point in ENDURANCE and one of the secondary end points in the dyslipidemia study. Other efficacy end points included responses to SEP-2, SEP-3 and International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Adverse events were recorded. Duration of erection (least squares mean ± s.e.) leading to successful intercourse was statistically superior in men receiving vardenafil versus placebo (12.8 ± 1.0 versus 5.5 ± 1.0 min; p<0.001 in ENDURANCE and 10.0 ± 0.8 versus 3.4 ± 0.8; p<0.001 in the dyslipidemia study), with a difference of 7.4 and 6.6 min, respectively, between treatment groups. Results for SEP-2, SEP-3 and IIEF-EF domain scores were consistent across studies and with stopwatch-assessed measures for duration of erection. Vardenafil was well tolerated. Duration of erection leading to successful intercourse is an important indicator of the efficacy of ED treatment. The stopwatch approach offers an alternative, precise and reproducible measure of efficacy. We propose this approach as a potential new paradigm for assessing the efficacy of ED treatments.

Does cardiovascular risk reduction alleviate erectile dysfunction in men with type II diabetes mellitus?

Veterans (N=41) with type II diabetes were enrolled in a behavioral and pharmacologic intervention for cardiac risk reduction for 4 weeks at the Providence Veterans Affairs Medical Center during 2004-2007 and were followed up 3 months post intervention. Erectile dysfunction (ED) was assessed using the 5-item version of the International Index of Erectile Function (IIEF-5). Participants experienced significant improvements in hemoglobin A1c (HbA1c), diastolic blood pressure and total cholesterol levels over the course of the intervention. Change in systolic and diastolic blood pressure and reduction in or maintenance of HbA1c below 7.0% were significantly associated with change in IIEF-5 (P=0.01, P=0.01, P=0.04, respectively). These results suggest that improved blood pressure and glycemic control in men with diabetes may lead to an improvement in ED.

Testosterone and ageing: what have we learned since the Institute of Medicine report and what lies ahead?

A 2003 report by the Institute of Medicine (IOM) surveyed the literature on the benefits and risks of testosterone replacement therapy in older men and identified knowledge gaps and research needs. This review summarises some key studies published since the IOM report. The possible relationship of testosterone to risk of prostate cancer remains a concern; however, no new evidence has emerged to suggest that testosterone replacement therapy increases the risk. Recent studies have demonstrated that hypogonadism in men may be more prevalent than previously thought, is strongly associated with metabolic syndrome, and may be a risk factor for type 2 diabetes and cardiovascular disease. Clinical studies have shown that testosterone replacement therapy in hypogonadal men improves metabolic syndrome indicators and cardiovascular risk factors. Maintaining testosterone concentrations in the normal range has been shown to contribute to bone health, lean muscle mass, and physical and sexual function, suggesting that testosterone replacement therapy may help to prevent frailty in older men. Based on current knowledge, testosterone replacement therapy is unlikely to pose major health risks in patients without prostate cancer and may offer substantial health benefits. Larger, longer-term randomised studies are needed to fully establish the effects of testosterone replacement therapy.

Managing enlarged prostate in primary care.

Assessment and treatment of benign prostatic hyperplasia, or enlarged prostate, has evolved considerably in recent years; clear evidence has accumulated for the progression of disease over time, the association between disease progression and negative outcomes, and the potential for medical management of this condition. Commensurate with the long-term preventive role of primary care, efforts can and should be made to treat the underlying condition of enlarged prostate as well as to manage the symptoms short-term. This review outlines evaluation of men presenting with lower urinary tract symptoms, examines the challenges for medical treatment and suggests how treatment choice can address these challenges.

Vessel caliber and branch-angle of human coronary artery branch-points.

Measurements were made of parent and branch vessel diameters and of the included angles of branch-points from postmortem human coronary arteriograms to determine the usefulness of theoretical equations predicting the relationships between parent and branch vessel caliber and between arterial caliber and branch-angle. The formulas were based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Size relationships between parent vessel and its branches were determined for 42 left main and 53 other epicardial coronary artery branch-points in hearts with angiographically normal arteries. Left main coronary artery branch-points were studied in 68 hearts with various degrees of angiographically defined coronary artery disease. Measured diameters (D) of parent and branch vessels corresponded well to the theoretical formula: (DParent)3 = (DBranch1)3 + (DBranch2)3....,in angiographically normal coronary arteries. The exponent, on the average, is less with increasing grades of vascular disease for left main coronary artery branch-points. Mean area ratio, the sum of the cross-sectional area of the branches divided by the area of parent vessel, decreased with greater arteriographic disease. Area ratio varies with changes in the relative calibers of branch vessels. Fifty-seven branch-angles were determined by graphic analysis of postmortem biplane coronary arteriograms. No relationship could be found between branch-angle and vessel caliber. The included angle between branches varied from 32 degrees to 124 degrees without respect to relative or absolute vessel calibers. The results of these postmortem measurements on human coronary arteriogram suggest that coronary artery caliber may adjust to minimize energy loss at the branch-point but that branch-angle is determined by other factors. Restudy of arteriograms suggests that branch-angle may be determined by branch vessel destination.