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Achieving Effective Risk-Factor Modification in Men

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Achieving Effective Risk-Factor Modification in Men Risk Factor Modification v2_Layout 1 20/05/2011 15:05 Page 1 TALKING POINTS 13 Achieving effective risk-factor modification in men MICHAEL KIRBY AND ROGER KIRBY Urological complaints in men provide healthcare professionals with an opportunity to modify risk factors, thus not only averting the progression of prostate cancer and benign prostatic hyperplasia, but also reducing the hazards of cardiovascular events in men presenting with erectile dysfunction. he concept of ‘risk’ is not well will translate into Tappreciated by most men. In the premature business world, risk, when adroitly judged, morbidity and can lead to significant rewards. By mortality. contrast, most men tend to be somewhat risk averse, not only financially, but also Risk prediction more importantly in terms of approaching has become a hot their health. Attitudes between the sexes topic, not only in vary, as does their willingness to seek cardiovascular medical help and advice. Women tend to disease, but also in localised prostate Figure 1. Helping seek help earlier and are much more likely cancer, benign prostatic hyperplasia (BPH) patients counter obesity to confide in friends and relatives. and erectile dysfunction (ED), and there are by encouraging lifestyle modification major opportunities to advise corrective (patient handout available from When men eventually do present to us treatment and/or lifestyle modification www.trendsinurology.com) in the surgery or clinic, we need to take accordingly. the opportunity to think about their future risk and modify those things that PROSTATE CANCER are modifiable. A subgroup of patients presenting with localised prostate cancer can certainly be From middle age onwards we all carry stratified as high risk. Traditionally, this a complex portfolio of risk factors, category has been based on the presenting including our family history, which are prostate-specific antigen (PSA) level and modified by our environment and the Gleason score, but recently D’Amico lifestyle. For some of us, these factors et al.1 identified the rate and extent of This article is modified from: Kirby R, Kirby M. Achieving effective risk-factor Michael Kirby, Visiting Professor, University of Hertfordshire and The Prostate modification in urological patients. Centre; Roger Kirby, Director, The Prostate Centre, London BJU Int 2008;101:793–4. TRENDS IN UROLOGY & MEN’S HEALTH MAY/JUNE 2011 www.trendsinurology.com Risk Factor Modification v2_Layout 1 20/05/2011 15:05 Page 2 TALKING POINTS 14 PSA rise (PSA kinetics or velocity) before anticipated to impair flow through the signal-transduction pathway shared diagnosis as another important variable. vessel at an earlier stage than in the latter. by growth factors such as vascular Patients identified as high risk in this Jackson et al.4 argued that men presenting endothelial growth factors or fibroblast respect should clearly be given priority with ED should be regarded as vascular growth factors. Statins might influence for potentially curative therapy, such as patients until proved otherwise, and re-endothelialisation by their effects on radical prostatectomy, after the risks investigated, with any significant mobilising, differentiating and improving and benefits have been clearly explained abnormalities treated. Advice about lipids the survival of endothelial progenitor to them, as their prognosis with no and blood-pressure-lowering therapy cells.8 It has been proposed that these intervention is poor. should obviously be offered, together mechanisms might all contribute to the with advice about lifestyle modification improved NO bioavailability. BENIGN PROSTATIC HYPERPLASIA regarding diet and exercise (Figure 1). Although the risks associated with BPH are Regular moderate to intense physical A recent meta-analysis revealed that a not life-threatening, progression of this exercise is well known to reduce the 1mmol/l reduction in LDL cholesterol disorder can certainly diminish the quality risk of cardiovascular disease and is translated into an 18 per cent reduction in of life. Moreover, if acute urinary retention beneficial for secondary prevention. In heart attack or stroke.9 Intriguingly, there is (AUR) develops, severe distress can result, addition to this, there is good evidence also emerging evidence that statins might which has been shown to persist for many that increasing physical activity can not only reduce PSA levels but also offer months after the actual event.2 The risk reduce the risk of certain types of cancer, some chemopreventative protection factors for BPH progression and AUR have osteoporosis, type 2 diabetes, depression, against prostate cancer.10 In addition, it been identified as: obesity and hypertension.5 If diabetes might be expected that statins would be • severe lower urinary tract symptoms mellitus is identified, there should be beneficial in ED; preliminary data on the • a prostate volume >30ml active intervention. beneficial effect of statins on patients with • an elevated PSA level (which in the ED were reported recently.11 absence of prostate cancer can serve as a CHOLESTEROL LOWERING surrogate for prostate volume). It has become understood that exercise LIFESTYLE MODIFICATION and weight reduction alone will yield An increased waist circumference The 5-alpha-reductase inhibitors beneficial effects on lipid profiles and and/or body mass index is significantly finasteride and dutasteride have both blood pressure, and improve ED.6 associated with increased cardiovascular been shown to reduce the risk of AUR However, if total and low-density risk, as well as all the other deleterious by more than half when matched against lipoprotein (LDL) cholesterol are components of the metabolic syndrome, placebo. Finasteride in combination significantly elevated, there is now including diabetes mellitus. Exhortation with the alpha-blocker doxazosin was abundant evidence that lowering these by clinicians to adopt a more sensible diet more effective in the Medical Therapy with a statin will result in a significant and to increase the amount of regular of Prostatic Symptoms study than reduction in cardiovascular risk. vigorous exercise is therefore in order. either agent alone in preventing This should help our patients get to a progression, which was defined as an Statins have various pleiotropic effects, with better PLACE (see Figure 1). The beneficial increase in symptom score of more vasculoprotective and cardioprotective effect of a high intake of fruit and than four points, the need for surgery, activity, which might be attributable, at vegetables has been reinforced by a or the development of complications least in part, to inhibition of vascular recently published meta-analysis.12 such as AUR. smooth muscle cell proliferation and the way they accelerate re-endothelialisation.7 CONCLUSIONS CARDIOVASCULAR DISEASE AND Their beneficial effects on endothelial The conclusions to be drawn from these ERECTILE DYSFUNCTION cells and on endothelial cell function data seem clear. Primary care physicians Evidence is also steadily accruing that ED appear to be related to improved nitric and urologists, when assessing their might be a harbinger of coronary artery oxide (NO) bioavailability. patients with cardiovascular risk, prostate disease and therefore risk of subsequent cancer, BPH or ED, should be thinking myocardial infarction.3 Certainly, the two Statins induce stability of endothelial not only about the ‘here and now’, but conditions share similar risk factors. As the NO synthase mRNA in endothelial cells, also the future prospects for the given mean diameter of the penile artery is only and promote endothelial NO synthase individual, providing them with the a small fraction of that of the coronary activity through a PI3K/Akt-dependent information to make personal choices vessels, atheroma in the former might be pathway, which is the common and get control. www.trendsinurology.com TRENDS IN UROLOGY & MEN’S HEALTH MAY/JUNE 2011 Risk Factor Modification v2_Layout 1 20/05/2011 15:05 Page 3 TALKING POINTS 15 Risk-factor modification, including impact on patients’ quality of life? BJU Int reendothelialisation. Circulation 2002; smoking cessation advice, is now a routine 2005;95:72–6. 105:3017–24. component of cardiovascular and diabetes 3 Kirby M, Jackson G, Simonsen U. 9 Cholesterol Trialists’ (CTT) Collaborators. management, and a similar approach could Endothelial dysfunction links erectile Efficacy and safety of cholesterol lowering be adopted in men with urological dysfunction to heart disease. Int J Clin treatment: prospective meta-analysis of complaints to avert the progression of Pract 2004;59:225–9. data from 90 056 participants in 14 prostate cancer and BPH, and also to 4 Jackson G, Rosen RC, Kloner RA, et al. The randomised trials of statins. Lancet reduce the hazards of cardiovascular second Princeton consensus on sexual 2005;366:1267–78. events in men presenting with ED. dysfunction and cardiac risk: new 10 Shannon J, Tewoderos S, Garzotto M, Significant risk reduction in all these guidelines for sexual medicine. J Sex Med et al. Statins and prostate cancer risk: disorders can be achieved with timely 2006;3:28–36. a case-control study. Am J Epidemiol lifestyle modification, pharmacotherapy 5 Alford L. What men should know about 2005;162:318–25. and surgical intervention.13 the impact of physical activity on their 11 Saltzman EA, Guay AT, Jacobson J. health. Int J Clin Pract 2010;64:1731–4. Improvement in erectile dysfunction in Declaration of interests: none 6 Eposito K, Giugliano F, Martedi E, et al. men with organic erectile dysfunction High proportions of erectile dysfunction by correlation of elevated cholesterol REFERENCES in men with the metabolic syndrome. levels: a clinical observation. J Urol 2004; 1 D’Amico AV, Hui-Chen M, Renshaw AA, Diabetes Care 2005;28:1201–3. 172:255–8. et al. Identifying men diagnosed with 7 Corsini A, Pazzucconi F, Pfister P, et al. 12 He FJ, Nawson CA, MacGregor GA. Fruit clinically localised prostate cancer who Inhibitor of proliferation of arterial and vegetable consumption and stroke: are at high risk for death from prostate smooth muscle cells by fluvastatin. meta-analysis of cohort studies. Lancet cancer. J Urol 2006;176:511–15.
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