Cardiovascular disease (CVD) is the leading cause of death globally, with an estimated 17.5 million deaths in 2012.  CVDs primarily affect the heart tissues and are precipitated by non-modifiable as well as modifiable risk factors. Recently, emerging risk factors such as low testosterone levels have been suggested to contribute to the development of CVD. [467-468] These studies have emphasized that people with lower testosterone levels are at increased risk of developing CVD and dying from this condition. [469-471]
For instance, a study by Malkin et al. involving over 900 men found that both total and bioavailable testosterone were significantly lower in men with coronary artery disease compared to those without heart disease.  The same study demonstrated a prevalence of low testosterone levels of 24% in men with coronary artery disease.
In the Rotterdam study, Hak et al. evaluated the association between total and bioavailable testosterone and aortic atherosclerosis (narrowing of the heart’s muscular pumping chamber) in 504 non-smoking men aged 55 years and above.  Researchers found that men with the highest testosterone levels had a risk reduction of 60–80% of severe aortic atherosclerosis compared to those with lower testosterone levels.
Another prospective study conducted by Muller et al. involving elderly men (mean age 77 years) showed that lower level of free testosterone is related to progression of intima–media thickness of the common carotid artery over 4 years.  This means that lower testosterone levels are strongly linked with narrowing of the arterial walls of the heart, which ultimately leads to poor blood circulation.
Promising new research suggests that men with low testosterone levels who are on testosterone replacement therapy (TRT) could have a lower risk of heart attack. To support this, Sharma et al. reported that normalization of testosterone levels through gels, patches, or injections is associated with reduced incidence of myocardial infarction (MI) and mortality among 83,010 male veterans who do not have pre-existing cardiovascular disease.  The study also found that men who were treated with testosterone but did not attain normal levels of the hormone did not achieve the same benefits as those whose testosterone levels did reach normal. This major study has the largest group of respondents and has the longest follow-up for testosterone replacement therapy ever conducted.
Testosterone plays a major role in the haemostatic/fibrinolytic system (system closely linked to control of inflammation). Androgens such as testosterone have anti-thrombotic action, which means that they have the ability to reduce the formation of blood clots.  This action can prevent the occurrence of heart attack since blood clots are the major cause of impaired blood circulation especially in the coronary artery, which supplies blood to the heart muscle. Webb et al. even reported that short-term administration of testosterone in the coronary artery induces dilation and increases coronary blood flow among 13 men with established coronary artery disease. 
In a meta-analysis of six short-term studies (mean, 23 weeks), Corona et al. reported that all of the studies enrolled patients with coronary heart disease who were treated with different formulations and doses of testosterone replacement therapy or placebo.  The results of these clinical trials showed that testosterone treatment was positively associated with a significant increase in treadmill test duration (168 seconds) and improvement in results of electrocardiogram (measures the electrical activity of the heart).
Similarly, the available studies of patients with heart failure (HF) who received testosterone replacement therapy have shown significant improvements in exercise capacity after 12 to 52 weeks of treatment.  The meta-analysis included four clinical trials with subjects suffering from heart failure. Researchers observed that combined results of the trials showed a significant increase in exercise capacity of almost 54 meters using the six-minute walk test after receiving testosterone replacement therapy.
A new multi-year study conducted by a team of researchers from the Intermountain Medical Center Heart Institute in Salt Lake City found that testosterone replacement therapy helped older men with abnormally low testosterone levels and pre-existing coronary artery disease reduce their risks of heart attacks, death and strokes.  The study also showed that patients who did not receive testosterone therapy were 80% more likely to suffer from an adverse event, suggesting that testosterone may help increase the lifespan of patients with heart disease.
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