Relationship Between Benign Prostatic Hyperplasia and History of Coronary Artery Disease

Relationship Between Benign Prostatic Hyperplasia and History of Coronary Artery Disease in Elderly Men

Kenneth M. Weisman, M.D., The Department of Surgery, Taylor Hospital, Ridley Park, Pennsylvania; Ghassem E. Larijani, Pharm.D. and Michael E. Goldberg, M.D., The Department of Anesthesiology, University of Medicine and Dentistry of New Jersey and Cooper Hospital/UMC, Camden, New Jersey; Mark R. Goldstein, M.D., The Department of Medicine, Crozer-Chester Medical Center, Upland, Pennsylvania.

Abstract

Study Objective: To assess the relationship between the occurrence of benign prostatic hyperplasia (BPH), an androgen-dependent disease, and coronary artery disease (defined as history of coronary artery bypass grafting, coronary angioplasty, myocardial infarction) in elderly men.
Design: Retrospective chart review.
Setting: Urology practice.
Patients: Seven hundred two elderly men aged 65-80 years.
Intervention: The men's charts were reviewed for data pertaining to coronary artery disease, risk factors for coronary artery disease, and serum prostate-specific antigen (PSA) levels. Men who had medical conditions, pharmacologic interventions, or surgical procedures that could alter PSA, and those taking lipid-lowering agents were not included.
Measurements and Main Results: PSA levels correlate positively with prostatic volume of BPH. In men with levels under 1.0 µg/L (no BPH) and over 1.0 µg/L (BPH present), the frequency of coronary artery disease was 9% and 29%, respectively (p<0.03). No significant differences were noted between groups in other accepted risk factors for coronary artery disease including age, smoking, diabetes mellitus, or hypertension.
Conclusion: Smooth muscle proliferation is an important and possibly androgen-dependent step in the development of atherosclerosis and BPH. Prospective studies are required to assess the effect of antiandrogens on atherosclerosis.

Introduction

It is well documented that the frequency of coronary artery disease (CAD) is influenced by gender as well as hormone status, with pre-menopausal women having a lower cardiac risk than men and postmenopausal women.[1] A large amount of observational data suggests that estrogen is protective when given postmenopausally, although a randomized study concluded that long-term benefits are offset by thromboembolic events in the short term.[2, 3] Although CAD is rare among premenopausal women, polycystic ovary syndrome, a disorder of hormone imbalance with relatively higher androgen levels, appears to increase the risk of atherosclerosis in younger women.[4] Little, however, has been written about hormone status of men and the frequency of atherosclerosis; although, for example, male pattern baldness (MPB) is an androgen-dependent condition that is a recognized risk factor for myocardial infarction.[5-7] In this retrospective study we evaluated the relationship between benign prostatic hyperplasia (BPH), another androgen-dependent disease, and CAD in men.

Benign prostatic hyperplasia is a condition in elderly men of periurethral hypertrophy of prostatic tissue that often results in voiding symptoms.[8] It appears to be androgen dependent since it does not develop in men who are castrated before puberty or progress as rapidly in men taking antiandrogens.[9-12] Similar to CAD, BPH is associated with high waist:hip ratio.[8,13,14] Histologic changes include proliferation of stromal and epithelial cells.[12] An abnormal stromal-epithelial interaction was implicated in the pathogenesis of BPH in that stroma (smooth muscle and connective tissue) develops the capacity to induce epithelial proliferation.[15]

The disorder can be difficult to quantify.[8] Symptoms of bladder outlet obstruction often do not correlate with volume of BPH. In the absence of other prostatic pathology serum prostate-specific antigen (PSA) levels correlate positively with prostatic volume of BPH, as determined by transrectal ultrasound, in a log linear fashion.[16,17] Since serum PSA is an objective measurement and easily obtained, we used it as a BPH surrogate. This technique allowed us to assess large numbers of men quickly in an objective yet noninvasive fashion.

Methods

Patients

Charts of 702 men seen in a urology practice over 2 years (1996-1998) were reviewed and data on age, smoking habits, presence of diabetes, and drug history were extracted. History of coronary angioplasty, myocardial infarction, stroke, transient ischemic attack, parental history of myocardial infarction, transurethral resection of the prostate (TURP), prostate biopsy, and serum PSA values were obtained. Patients were considered to have CAD if they had a history of myocardial infarction, coronary artery bypass grafting (CABG), or coronary angioplasty. Only men aged 65-80 years were included.

In the absence of other prostatic pathologies, PSA levels correlate with volume of BPH.[16,17] In elderly men they are influenced by the volume of BPH, prostatic carcinoma, prostatic inflammation, or prostatic trauma. To ensure that PSA levels reflected only the volume of BPH, patients were excluded if they had any condition, had undergone any procedure, or had been exposed to any drug known to change the value. Thus in the remaining patients, PSA level would correlate with volume of BPH. Urinary infection, prostatitis, various transurethral procedures (cystoscopy), Foley catheters, and prostatic biopsy are all known to increase serum PSA.[18] Therefore, no patient with these diagnoses or individuals who had undergone these procedures within 6 months of data collection were included. Since prostatic carcinoma also increases the value, men with levels of 4.0-10.0 µg/L were included only if prostatic biopsies were negative. Also excluded were men with prostatic carcinoma and those with PSA above 10 µg/L who were thought to be at risk for prostatic carcinoma despite negative biopsies.[18] A history of finasteride therapy resulted in exclusion since this drug can independently reduce PSA levels, as well as independently inhibit or shrink BPH.[9-12] No patient who had undergone TURP was included since this procedure reduces the amount of BPH and therefore reduces serum PSA.[19] Men who had taken drugs to lower serum lipids were eliminated since these agents can independently alter cardiac risk.[20, 21]

Serum PSA was measured by microparticle enzyme immunoassay (Abbott Laboratories, Abbott Park, IL). Patients were categorized into two groups based on PSA levels: 1.0 µg/L or less (no BPH present, group 1) and greater than 1.0 µg/L but less than 10.0 µg/L (BPH present, group 2).

Data Analysis

Data were analyzed by x2 statistics and unpaired Student's t test. A p value less than 0.05 was considered significant. Data are presented as mean ± SD.

Results

Of the 702 charts reviewed, 140 met inclusion and exclusion criteria, 32 in group 1 (no BPH present) and 108 in group 2 (BPH present). The groups did not differ significantly in frequency of accepted risk factors for atherosclerosis, including age, hypertension, diabetes mellitus, smoking, and parental history of myocardial infarction (Table 1). Patients in group 1 had significantly lower frequency of self-reported myocardial infarction and CABG compared with those in group 2 (9% vs 29%, p<0.03).

Discussion

Estrogen provides protection against CAD in women both before and after menopause, although one trial questioned the utility of oral estrogen for secondary prevention of CAD in postmenopausal women due to early thrombo-embolic events.[1-3] The protective long-term effect of estrogen is attributed mostly to its direct effects on target vascular tissues rather than to changes in serum lipids.[22] Male gender is a risk factor for atherosclerotic disease. Several reports considered the effects of androgens on serum lipids.[23,24] A complete explanation for the increased risk in men remains to be found, especially since many cardiac events occur in individuals with little or no increase in serum lipids[25]; however, we believe that the effects of androgen on target vascular tissues in men should be considered a possible explanation.

Our data demonstrated a relationship between the failure of men to develop BPH and failure to develop CAD. Elderly men who did not develop BPH to any extent, as evidenced by PSA values of 1.0 µg/L or below, had a significantly lower frequency of CAD than those with BPH with higher levels. Since BPH is androgen dependent, this suggests that atherosclerosis may be as well, at least in part. Vascular smooth muscle cell proliferation is an important step in the development of atherosclerosis,[22,26] and is likely to be androgen dependent.[27,28] We speculate that in subjects in group 1, smooth muscle proliferation was perhaps less responsive to androgen, so they had neither BPH nor atherosclerosis.

In conclusion, patients with no BPH had a lower frequency of CAD than those with BPH. Prospective studies are necessary to reexamine the relationship between the disorders. As antiandrogens can inhibit the development of both BPH and MPB,[7,10,11] prospective studies are also required to evaluate their effects, if any, on the development of atherosclerosis.