Coronary Artery Disease Abstracts 1 – Hormone

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Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors
            (Akishita et al., 2010) Download
OBJECTIVE: Recent epidemiological studies have found that testosterone deficiency is associated with higher mortality largely due to cardiovascular (CV) disease in community-dwelling older men. We investigated whether a low plasma testosterone level could predict cardiovascular events in middle-aged Japanese men with coronary risk factors. METHODS: One hundred and seventy-one male outpatients (30-69 years old, mean+/-SD=48+/-13 years) who had any coronary risk factor (hypertension, diabetes, dyslipidemia, smoking, and obesity) without a previous history of CV disease were followed up. At baseline, the subjects underwent examination of coronary risk factors, measurement of flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular endothelial function and assays of plasma total testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol and cortisol. RESULTS: During the mean follow-up period of 77 months, a total of 20 CV events occurred. Kaplan-Meier survival analysis by tertile of plasma hormone levels revealed that the subjects with the lowest testosterone tertile were more likely to develop CV events than those with the highest tertile (P<0.01 by log-rank test). Cox proportional hazards models showed that the subjects with the lowest tertile of plasma testosterone (<14.2 nmol/L) had an approximately 4-fold higher CV event risk compared to those with the higher testosterone tertiles after adjustment for coronary risk factors including medication and FMD (unadjusted hazard ratio, 3.61; 95% CI, 1.47-8.86: multivariate-adjusted hazard ratio, 4.61; 95% CI, 1.02-21.04). Multivariate analysis did not show any significant association of DHEA-S, estradiol or cortisol with CV events. CONCLUSIONS: A low plasma testosterone level is associated with CV events in middle-aged Japanese men, independent of coronary risk factors and endothelial function. This is the first report to show the relationship between endogenous testosterone and CV events in Asian population.


Prospective association of serum androgens and sex hormone-binding globulin with subclinical cardiovascular disease in young adult women: the "Coronary Artery Risk Development in Young Adults" women's study
            (Calderon-Margalit et al., 2010) Download
CONTEXT: The role of endogenous androgens and SHBG in the development of cardiovascular disease in young adult women is unclear. OBJECTIVE: Our objective was to study the prospective association of serum androgens and SHBG with subclinical coronary and carotid disease among young to middle-aged women. DESIGN AND SETTING: This was an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort study with 20 yr of follow-up. PARTICIPANTS: Participants included 1629 women with measurements of serum testosterone and SHBG from yr 2, 10, or 16 and subclinical disease assessment at yr 20 (ages 37-52 yr). MAIN OUTCOME MEASURES: Coronary artery calcified plaques (CAC) and carotid artery intima-media thickness (IMT) were assessed at yr 20. The IMT measure incorporated the common carotid arteries, bifurcations, and internal carotid arteries. RESULTS: SHBG (mean of yr 2, 10, and 16) was inversely associated with the presence of CAC (multivariable adjusted odds ratio for women with SHBG levels above the median = 0.59; 95% confidence interval = 0.40-0.87; P = 0.008). SHBG was also inversely associated with the highest quartile of carotid-IMT (odds ratio for women with SHBG levels in the highest quartile = 0.56; 95% confidence interval = 0.37-0.84; P for linear trend across quartiles = 0.005). No associations were observed for total or free testosterone with either CAC or IMT. CONCLUSION: SHBG levels were inversely associated with subclinical cardiovascular disease in young to middle-aged women. The extent to which low SHBG is a risk marker or has its own independent effects on atherosclerosis is yet to be determined.

Thyroid hormone and coronary artery disease: from clinical correlations to prognostic implications
            (Coceani et al., 2009) Download
BACKGROUND: Overt thyroid dysfunction, hypothyroidism in particular, may lead to coronary artery disease (CAD). Whether more subtle anomalies of thyroid hormone metabolism influence the progression of CAD remains a matter of speculation. HYPOTHESIS: The occurrence of CAD and long-term prognosis in patients without a history of either primary thyroid disease, myocardial infarction, or chronic heart failure is related to serum levels of biologically active free triiodothyronine (fT3). METHODS: The cohort consisted of 1047 clinically and biochemically euthyroid patients (median age 65.6 y and 69% male) who underwent coronary angiography in our institute for suspected CAD. RESULTS: Lower fT3 levels were predictive of both single-vessel (p = 0.012) and multivessel (p = 0.009) CAD. Through a multivariate logistic regression analysis, fT3 was still linked to the presence of CAD (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.34-0.68, p < 0.001). After a mean follow-up of 31 months, the survival rate was 95% and total mortality (log-rank 6.75, p = 0.009), as well as cardiac mortality (log-rank 8.26, p = 0.004), was greater among patients with low T3 (fT3 < 2.10 pg/mL) syndrome. At subsequent multivariate Cox regression analysis, the association between low T3 syndrome and survival was maintained (total mortality HR: 1.80, 95% CI: 1.05-3.10, p = 0.034; cardiac mortality HR: 2.58, 95% CI: 1.13-5.93, p = 0.025). CONCLUSIONS: In this selected population, fT3 levels were inversely correlated to the presence of CAD and low T3 syndrome conferred an adverse prognosis, even after adjusting for traditional coronary risk factors.

Effects of chronic testosterone administration on myocardial ischemia, lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease
            (Cornoldi et al., 2010) Download
BACKGROUND: The evidence of antiatherogenic and vasodilatatory effects of testosterone (T) suggest a possible role of the lack of this hormone in the development and pathophysiology of coronary artery disease (CAD). Aim of the present study was to evaluate the effects of oral administration of testosterone undecanoate during a period of three months on serum lipid levels and on the occurrence of anginal attacks and daily ischemic episodes in patients with CAD. METHODS AND RESULTS: Eighty seven (87) diabetic male subjects (mean age: 74+/-7 years) with proven CAD were randomized to a 12 week treatment with either T undecanoate (40 mg administered three daily) or placebo (P) in a double blind protocol. Weekly episodes of angina attacks, number of ischemic episodes daily and total ischemic burden on ambulatory ECG Holter were evaluated at baseline and at the end of the study. Serum total cholesterol and triglyceride concentrations were also measured at the same time points. Compared to P, T significantly reduced the number of anginal attacks/weeks of 34% (p<0.05); the silent ischemic episodes of 26% (p<0.05), and the total ischemic burden of 21% (p<0.05) on ambulatory ECG monitoring. After 12 weeks total cholesterol, plasma triglycerides and HOMA index were significantly reduced in the T group compared to P group. CONCLUSIONS: Three months administration of T has beneficial effect on serum cholesterol and triglyceride levels in patients with CAD and reduces the number of anginal attacks, and ischemic episodes. These effect may be related to the metabolic and vasoactive properties of the hormone. Further studies are needed in order to assess the long term relevance of these effects.


Nonlinear association between serum testosterone levels and coronary artery disease in Iranian men
            (Fallah et al., 2009) Download
Previous studies have shown controversial results about the role of androgens in coronary artery disease (CAD). We performed this study to examine and compare the relationship between androgenic hormones and CAD using conventional linear statistical techniques as well as novel non-linear approaches. The study was conducted on 502 consecutive men who were referred for selective coronary angiography at Tehran Heart Center due to different indications. We studied the relationship between androgenic hormones and CAD by using the generalized linear models, generalized additive models, and neural networks. Free testosterone (fT), total testosterone (tT) and dehydroepiandrosterone sulfate levels in patients with significant CAD versus normal individuals were 6.69 +/- 3.20 pg/ml, 16.60 +/- 6.66 nm/l, and 113.38 +/- 72.9 microg/dl versus 7.12 +/- 3.58 pg/ml, 15.82 +/- 7.26 nm/l, and 109.03 +/- 68.19 microg/dl, respectively (P > 0.05). The Generalized linear models was unable to show any significant relationship between androgenic hormones and CAD, while generalized additive model and neural networks supported the significant effect of androgenic hormones on CAD. This finding suggests a nonlinear association of tT levels with CAD: lower levels have a preventive effect on CAD, whereas higher values increase the risk of CAD. Emphasizing the non-linearity of the variables may provide new insight into the possible explanation of the effect of androgenic hormones on CAD.

Sex hormone ratio changes in men and postmenopausal women with coronary artery disease
            (He et al., 2007) Download
OBJECTIVE: The goal of this study was to investigate the potential role of sex hormones in coronary atherosclerosis in both men and postmenopausal women. DESIGN: A total of 258 male and 236 female postmenopausal participants with angiographically defined stable coronary artery disease (CAD) were enrolled. We measured the levels of estradiol (E2), progesterone (P), testosterone (T), follicle-stimulating hormone, and luteinizing hormone in the participants and in 156 male and 132 female disease-free and age-matched controls using commercially available radioimmunoassay kits. RESULTS: In the male study participants and control subjects, the levels of E2 and P differed slightly in opposing directions; however, these differences were not significantly different, nor were there significant differences in T. However, the ratio of E2 to P in participants was significantly (P < 0.01) lower (even after adjustments for age and body mass index) than in the control subjects (mean +/- SEM: 70.2 +/- 56.4 vs 90.7 +/- 59.5, respectively). In the postmenopausal women, a slight decrease in E2 and increases in P and T in participants were not significantly different from levels in the control group. However, the E2 to P and E2 to T ratios were significantly (P < 0.01) lower (before and after adjustments for age and body mass index adjustments) in the participants relative to the control subjects (38.7 +/- 28.4 vs 49.6 +/- 36.3 and 46.5 +/- 37.6 vs 60.6 +/- 40.8, respectively). Correlation analyses demonstrated that the sex hormone ratio changes in both men and postmenopausal women were related with atherogenic blood lipoprotein changes. In both the male and female groups, levels of follicle-stimulating hormone and luteinizing hormone did not differ significantly between the participants and controls, and correlation analyses revealed no association between these hormones and the ratio of E2 to P in males and the ratios of E2 to P and E2 to T in females (r < 0.2, P > 0.05). Multiple regression analyses demonstrated that age and the presence of CAD were significantly and independently associated with the E2-to-P ratio in men and the E2-to-P and E2-to-T ratios in women and that E2-to-P ratio and low-density lipoprotein cholesterol level were significant independent predictors of CAD in males; E2-to-P and E2-to-T ratios and low-density lipoprotein cholesterol level were significant predictors of CAD in women. CONCLUSIONS: In both men and postmenopausal women with angiographic CAD, there were significant differences (relative to age-matched control subjects) in sex hormone ratios, suggesting an abnormality that could influence coronary health. A lower E2-to-P ratio may be associated with the male disposition to coronary atherosclerosis, whereas lower E2-to-P and E2-to-T ratios may be associated with the same condition in females.

Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus
            (Jackson et al., 2010) Download
* A significant proportion of men with erectile dysfunction (ED) exhibit early signs of coronary artery disease (CAD), and this group may develop more severe CAD than men without ED (Level 1, Grade A). * The time interval among the onset of ED symptoms and the occurrence of CAD symptoms and cardiovascular events is estimated at 2-3 years and 3-5 years respectively; this interval allows for risk factor reduction (Level 2, Grade B). * ED is associated with increased all-cause mortality primarily due to increased cardiovascular mortality (Level 1, Grade A). * All men with ED should undergo a thorough medical assessment, including testosterone, fasting lipids, fasting glucose and blood pressure measurement. Following assessment, patients should be stratified according to the risk of future cardiovascular events. Those at high risk of cardiovascular disease should be evaluated by stress testing with selective use of computed tomography (CT) or coronary angiography (Level 1, Grade A). * Improvement in cardiovascular risk factors such as weight loss and increased physical activity has been reported to improve erectile function (Level 1, Grade A). * In men with ED, hypertension, diabetes and hyperlipidaemia should be treated aggressively, bearing in mind the potential side effects (Level 1, Grade A). * Management of ED is secondary to stabilising cardiovascular function, and controlling cardiovascular symptoms and exercise tolerance should be established prior to initiation of ED therapy (Level 1, Grade A). * Clinical evidence supports the use of phosphodiesterase 5 (PDE5) inhibitors as first-line therapy in men with CAD and comorbid ED and those with diabetes and ED (Level 1, Grade A). * Total testosterone and selectively free testosterone levels should be measured in all men with ED in accordance with contemporary guidelines and particularly in those who fail to respond to PDE5 inhibitors or have a chronic illness associated with low testosterone (Level 1, Grade A). * Testosterone replacement therapy may lead to symptomatic improvement (improved wellbeing) and enhance the effectiveness of PDE5 inhibitors (Level 1, Grade A). * Review of cardiovascular status and response to ED therapy should be performed at regular intervals (Level 1, Grade A).

Cardiovascular disease and androgens: a review
            (Kaushik et al., 2010) Download
Globally, cardiovascular disease is the single largest cause of mortality. The differences in pattern of cardiovascular disease between the two genders have not been explained properly. The spotlight has largely been focused on estrogens but no conclusive evidence has proven its role in reducing the incidence of cardiovascular disease. Consequently, androgens have attracted significant interest in explaining the gender difference in cardiovascular disease. More studies in last two decades have increased our knowledge about the effects of androgens on cardiovascular disease progression. Evidence for age related fall in testosterone levels in males and increasing cardiovascular events with age had lead to the postulation of idea of 'andropause or male menopause'. Unfortunately, for the last few decades the androgens have been highlighted as agents of abuse among athletes all over the world. There have been multiple reports of their association with sudden cardiac death and adverse cardiovascular outcomes when abused. Contrastingly, there has been an increasing prescription use of testosterone supplementation in various conditions related to androgen deficiency state and for many other off-label indications. Human observational studies have mostly concluded that men with lower testosterone levels tend to have higher incidence of coronary artery disease. Emerging evidence supports that lower androgen levels predict poor cardiovascular risk profile. Role with supplementation of testosterone for cardiovascular disease is being studied in both primary and secondary prevention stages and its safety being evaluated. This is an appropriate time to review the role of androgens specifically from a cardiovascular standpoint.


Extremes of endogenous testosterone are associated with increased risk of incident coronary events in older women
            (Laughlin et al., 2010) Download
Context: Few studies have examined whether endogenous testosterone is associated with the development of coronary heart disease (CHD) in women. Objective: This study tested the association of total testosterone (total T) and bioavailable T (BioT) levels with risk of incident coronary events among older community-dwelling women. Design, Setting, and Participants: This was a prospective, population-based study of 639 postmenopausal women, aged 50-91 (mean, 73.8) yr who had serum testosterone measurements at baseline (1984-87) and who were followed for incident CHD events through 2004. Main Outcome Measures: A total of 134 incident CHD events occurred during follow-up [45 nonfatal myocardial infarctions, 79 fatal myocardial infarctions, and 10 coronary revascularizations]. Results: The median follow-up was 12.3 yr. Age-adjusted CHD risk estimates were similar for the four highest total T quintiles relative to the lowest, suggesting a low threshold. In age-adjusted analyses, the lowest total T quintile (</=80 pg/ml) was associated with a 1.62-fold increased risk of incident CHD [95% confidence interval (CI), 1.10-2.39] compared to higher levels. BioT showed a U-shaped association with incident CHD. Age-adjusted risk for the lowest and highest BioT quintiles relative to the third were 1.79 (95% CI, 1.03-3.16) and 1.96 (95% CI, 1.13-3.41), respectively. Additional adjustment for lifestyle, adiposity, estradiol, and ovarian status, or for CHD risk factor covariates, had minimal influence on results. Conclusions: An optimal range of testosterone may exist for cardiovascular health in women, with increased risk of CHD events at low levels of testosterone overall and at high levels of the bioavailable fraction of testosterone.

Testosterone as a modulator of vascular behavior
            (Littleton-Kearney and Hurn, 2004) Download
Male sex is an acknowledged risk factor for many forms of cardiovascular disease, and vascular disease prevalence patterns appear to be different in men versus women. The vascular properties of the principal mammalian androgen, testosterone, are complex and linked to dose, duration of exposure, presence of underlying vascular disease, and, possibly, biological sex. Data from isolated vessels and animal models suggest that pharmacological doses of testosterone, or its potent intracellular metabolite dihydrotestosterone, produce vasodilation. Testosterone's major effect on vascular beds at physiologic concentrations remains unclear, with documentation of both vasodilatory and vasoconstrictive actions. Results of various studies suggest that testosterone can alter vascular tone through both endothelium-dependent and endothelium-independent mechanisms in a variety of vascular beds and vessel types. Testosterone's endothelium-dependent effects are likely mediated at least in part through nitric oxide (NO) elaboration, whereas mechanisms of endothelium-independent effects involve 1 or more types of smooth muscle ion conductance channels. Data from clinical studies indicate that, in men, androgen replacement may provide beneficial effects when coronary artery disease is present. Conversely, in women, testosterone may augment existing hypertension, increase risk for cardiovascular events, or promote atherogenesis. However, it should be emphasized that most of these observations are anecdotal or come from small-scale clinical studies, and limited information is available in women. New research is required to understand the potential efficacy of androgen therapy, or lack thereof. This review focuses on current understanding of testosterone's physiological effects on vascular behavior and of testosterone's putative role in vascular health and disease.

Postmenopausal hormones and coronary artery disease: potential benefits and risks
            (Lobo, 2007) Download
Various secondary prevention trials, including the Women's Health Initiative (WHI0, assessing the effects of hormone therapy (HT) on coronary artery disease (CAD) showed no benefit, and a trend towards early harm. However, in the WHI trial, there was a significant trend for decreasing CAD with time. The observational arms of WHI for both estrogen and estrogen/progestin suggested results which were similar to the cardioprotective effects reported in earlier observational studies. Women in these observational trials initiated hormones at a younger age and were generally healthier than women in the randomized trials. Hypotheses have been generated to explain the phenomenon of early harm, based on the induction of plaque instability in the older woman with existent significant atherosclerosis. A report of over 7000 early postmenopausal women initiating prospective trials on hormonal use did not find any evidence suggesting early harm. In the estrogen-only arm of the WHI trial, an analysis of the 50-59-year-old age group showed a near statistical decrease in coronary events: 63 (0.36-1.08), and a statistically significant reduction in a global coronary score, 0.66 (0.45-0.96). In a pooled analysis of 23 randomized clinical trials of hormonal therapy, those women within 10 years of menopause had a significant reduction in coronary events, 0.68 (0.48-0.96). Recent publications from WHI have shown a significant trend for reduced CAD and total mortality in younger women, as well as a reduced coronary calcium score when estrogen alone was given. In that neither aspirin nor statins have been shown to afford a statistical primary benefit for reducing CAD, the benefit of estrogen remains an attractive yet unproven possibility for younger women. In conclusion, while it is clear that HT has no place in the treatment of older women with CAD, emerging evidence strongly suggests a possible coronary benefit in younger healthy women.

Assessment of estrogen status as a marker of prognosis in women with symptoms of suspected coronary artery disease presenting for stress testing
            (Morise, 2006) Download
Estrogen status (ES) has previously been shown to be a marker of angiographic outcome in women. In light of this finding, a reevaluation of ES as a marker of prognosis was undertaken. Two thousand one hundred forty-three women who underwent stress testing for symptoms of suspected coronary disease were studied. ES was defined according to menopausal, ovarian, and hormone replacement therapy status. The end points of interest were all-cause mortality, cardiac death, and nonfatal myocardial infarction. Survival analysis was performed using the Kaplan-Meier method and Cox regression analysis with censoring at revascularization. Compared with 1,362 ES-positive women, the 781 ES-negative women had a higher frequency of unfavorable end points (all-cause death: ES positive 31 [2.3%] vs ES negative 94 [12%], p < 0.0001, cardiac death: ES positive 11 [0.8%] vs ES negative 38 [4.9%], p < 0.0001, and nonfatal myocardial infarction: ES positive 11 [0.8%] vs ES negative 17 [2.2%], p = 0.007). The Kaplan-Meier curve analysis indicated that ES was a marker of cardiac risk (p < 0.0001) in all women, as well as in postmenopausal women. Multivariate Cox regression analysis revealed that ES was an independent marker of risk (p < 0.001) when considered with other standard risk factors. Using logistic regression and area under the curve analyses, ES had incremental value compared with standard risk factors. In conclusion, ES appears to be an easily discernible independent marker of risk that provides incremental prognostic information compared with standard clinical variables in women with symptoms of suspected coronary disease presenting for stress testing.

Androgens up-regulate atherosclerosis-related genes in macrophages from males but not females: molecular insights into gender differences in atherosclerosis
            (Ng et al., 2003) Download
OBJECTIVES: This study investigated the effects of androgens on gene expression in male- and female-donor macrophages. BACKGROUND: Men have more severe coronary disease than women. Androgen exposure increases foam cell formation in male but not female macrophages, and male macrophages express >4-fold more androgen receptor messenger ribonucleic acid than female macrophages. Therefore, androgen exposure may have gender-specific and potentially pro-atherogenic effects in macrophages. METHODS: Utilizing complementary deoxyribonucleic acid arrays, we studied the effects of a pure androgen (dihydrotestosterone, 40 nmol/l) on human monocyte-derived macrophages from healthy male and female donors (n = 4 hybridizations; 2 men, 2 women). Differential expression of atherosclerosis-related genes was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in five male and five female donors. Functional corroboration of foam cell formation-related findings was undertaken by experiments using (125)I-acetylated low-density lipoprotein (AcLDL). RESULTS: In male macrophages, androgen treatment produced differential up-regulation of 27 genes concentrated in five functional classes: 1) lipoprotein processing; 2) cell-surface adhesion; 3) extracellular signaling; 4) coagulation and fibrinolysis; and 5) transport protein genes. By contrast, none of 588 genes were up-regulated in female macrophages. By RT-PCR, we confirmed the gender-specific up-regulation of six of these atherosclerosis-related genes: acyl coenzyme A:cholesterol acyl transferase I, lysosomal acid lipase (LAL), caveolin-2, CD40, vascular endothelial growth factor-165 receptor, and tissue factor pathway inhibitor. Functionally, androgen-treated male macrophages showed increased rates of lysosomal AcLDL degradation, by 45% to 75% after 15 to 20 h of (125)I-AcLDL incubation (p = 0.001), consistent with increased LAL activity. CONCLUSIONS: Androgens increase expression of atherosclerosis-related genes in male but not female macrophages, with functional consequences. These findings may contribute to the male predisposition to atherosclerosis.

Baldness and coronary artery disease: the dermatologic point of view of a controversial issue
            (Rebora, 2001) Download
OBJECTIVE: Several articles, most of them written by nondermatologists, have stressed that bald men have a higher risk for coronary artery disease than men who are not bald. This study was performed to evaluate the validity of such conclusions from a dermatologic point of view. DESIGN: A review of the 24 articles in literature from 1954 to 1999 as provided by MEDLINE and a previous review. RESULTS: Five articles contained simple comments; 1 was a review of the previous literature; and 3 dealt only with the lipid profile. The remaining 15 articles dealt with coronary artery disease and baldness, and 9 of these concluded that there is a relationship between the 2 conditions, especially in younger subjects with severe early-onset androgenetic alopecia. CONCLUSIONS: Baldness did not coincide with androgenetic alopecia in some of the articles examined, which makes it difficult to settle the issue. Subjects who develop baldness before their 30s may have a higher risk for coronary artery disease than other men, and they may be individuals with early-onset androgenetic alopecia who also present with particularly elevated dihydrotestosterone-testosterone ratios. The baldness theory should be included as a secondary hypothesis in large epidemiological studies of coronary artery disease. Such studies should include dermatologic expertise for accurate, cost-effective evaluation of baldness.

 

Low testosterone levels are associated with coronary artery disease in male patients with angina
            (Rosano et al., 2007) Download
Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58+/-4 years, range 43-72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8+/-6.5 and 13.5+/-5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0+/-1.5 vs 6.6+/-1.9 IU/l and 7.9+/-2.1 vs 4.4+/-1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84+/-0.45 vs 1.19+/-0.74 nmol/l, P<0.01 and 10.7+/-1.4 vs 13.3+/-3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=-0.52, P<0.01). In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.

Testosterone and coronary artery disease
            (Schwarcz and Frishman, 2010) Download
Cardiovascular disease remains the leading cause of death in most of the developed world despite advances in both prevention and treatment. At the same time, the incidence rates of cardiovascular disease differ greatly between the genders, with men more likely than women to manifest ischemic heart disease. This observation has prompted new research initiatives to explain the discrepancy in heart disease prevalence and incidence between the sexes. Whether androgens affect cardiovascular disease adversely remains a contentious issue, with some data pointing to a deleterious effect of androgens on lipid profiles, and other studies revealing androgens' possible benefits on cardiovascular function. This review will examine the relationship between the endogenous production of androgen as well as the exogenous replacement of testosterone in men and the possible links to cardiovascular disease. The role of testosterone in male cardiovascular health is not completely understood, and additional studies are needed to explain its effect on atherosclerosis and its complications.

The association between androgen levels and premature coronary artery disease in men
            (Turhan et al., 2007) Download
OBJECTIVE: The relationship between androgens and the risk of development of coronary artery disease has not been clarified well. This study was planned to determine the relationship between serum androgen levels and premature development of coronary artery disease in men. METHODS: Sixty-nine men below 45 years of age with documented coronary artery disease (mean age 41.0+/-4.7) constituted the study group. Control group consisted of 56 men with similar age and normal coronary angiograms (mean age 41.3+/-3.8). Total and free testosterone, estradiol, and fasting plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol, and triglyceride levels were measured, and compared between the two groups. RESULTS: Mean age, body mass index, and the frequency of hypertension were similar between the two groups; however, diabetes mellitus, smoking, hyperlipidemia, and family history of coronary artery disease were more frequent in the coronary artery disease group. Total and free testosterone levels of the patients with coronary artery disease were significantly lower than those of controls, whereas estradiol levels did not differ. Multivariate logistic regression analysis revealed that free testosterone levels (P=0.014; odds ratio=0.90; 95% confidence interval=0.87-0.99), hyperlipidemia (P<0.001; odds ratio=8.2; 95% confidence interval=3.17-21.0), and smoking (P=0.026; odds ratio=3.12; 95% confidence interval=1.15-8.48) were independent predictors of premature coronary artery disease. Moreover, using receiver operating characteristic analysis, patients with free testosterone levels below the cut-off value of 17.3 pg/ml had an adjusted 3.3-fold risk of developing premature coronary artery disease compared to those with free testosterone levels above the cut-off level (odds ratio=3.3; 95% confidence interval=1.57-6.87). CONCLUSION: A low level of free testosterone may be related to the development of premature coronary artery disease.


Testosterone and coronary artery disease in men
            (Webb and Collins, 2010) Download
Coronary artery disease (CAD) is the leading cardiovascular cause of death, and in men, endogenous testosterone concentrations are inversely related to the extent and severity of CAD. Testosterone is known to affect a number of risk factors for CAD and has effects on vascular tone, vasoreactivity and blood flow of blood vessels beyond the reproductive system, indicating that testosterone may be involved in the pathogenesis of CAD. In this review we will present and discuss the actions of endogenous testosterone and testosterone treatment on risk factors for CAD, on the blood vessel wall and blood flow, and on atheroma development and progression, and discuss the potential for testosterone use in men with CAD.

Prevention of coronary artery disease in men: Male hormone, female hormone, or both?
            (Yang et al., 2010) Download
Sex hormones play an important role in coronary artery disease. Although both male and female hormones have been well-documented to be able to influence vascular biology, the preventive use of sex hormones in CAD is not established. Recent progress suggests a necessity of rethinking of the use of sex hormones for CAD in both sexes. We hypothesize that a long-term and appropriate low-dose combination of male hormone and female hormone could be an effective preventive strategy for men with a high risk of but not developed CAD. This hypothesis is supported by the fact that estrogen has favorable profiles on several key CAD-associated risk factors regardless of sexes. Testosterone supplementation has been linked to a reduced risk of CAD specifically in men. In animal models the reduced risk of CAD in males administrated with testosterone is due to the conversion of testosterone into estrogen; and sex hormone ratio changes rather than each individual sex hormone were found to be the predictor of CAD in a human study, suggesting the importance of a proper ratio of estrogen:testosterone in the development of CAD. In addition, the controversy surrounding the use of hormone replacement therapy in women in turn indicates a potential beneficial effect of sex hormones in men in the prevention of CAD because of the fundamental difference between sexes. Therefore, the combined use of estrogen and testosterone for CAD in men deserves a full investigation and could provide useful information in understanding of the preventive and/or therapeutic application of sex hormones in both sexes.

 


References

Akishita, M., et al. (2010), ‘Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors’, Atherosclerosis, 210 (1), 232-36. PubMed: 19963216
Calderon-Margalit, R., et al. (2010), ‘Prospective association of serum androgens and sex hormone-binding globulin with subclinical cardiovascular disease in young adult women: the “Coronary Artery Risk Development in Young Adults” women’s study’, J Clin Endocrinol Metab, 95 (9), 4424-31. PubMed: 20554712
Coceani, M., et al. (2009), ‘Thyroid hormone and coronary artery disease: from clinical correlations to prognostic implications’, Clin Cardiol, 32 (7), 380-85. PubMed: 19609889
Cornoldi, A., et al. (2010), ‘Effects of chronic testosterone administration on myocardial ischemia, lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease’, Int J Cardiol, 142 (1), 50-55. PubMed: 19361872
Fallah, N., et al. (2009), ‘Nonlinear association between serum testosterone levels and coronary artery disease in Iranian men’, Eur J Epidemiol, 24 (6), 297-306. PubMed: 19357974
He, H., et al. (2007), ‘Sex hormone ratio changes in men and postmenopausal women with coronary artery disease’, Menopause, 14 (3 Pt 1), 385-90. PubMed: 17108845
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Kaushik, M., S. P. Sontineni, and C. Hunter (2010), ‘Cardiovascular disease and androgens: a review’, Int J Cardiol, 142 (1), 8-14. PubMed: 19923015
Laughlin, G. A., V. Goodell, and E. Barrett-Connor (2010), ‘Extremes of endogenous testosterone are associated with increased risk of incident coronary events in older women’, J Clin Endocrinol Metab, 95 (2), 740-47. PubMed: 19934360
Littleton-Kearney, M. and P. D. Hurn (2004), ‘Testosterone as a modulator of vascular behavior’, Biol Res Nurs, 5 (4), 276-85. PubMed: 15068657
Lobo, R. A. (2007), ‘Postmenopausal hormones and coronary artery disease: potential benefits and risks’, Climacteric, 10 Suppl 2 21-26. PubMed: 17882668
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