PubMed | Google ScholarSee all References In comparison, a study of 132 patients evaluated by penile duplex ultrasonography after intracorporeal papaverine injection found that hypertension alone was not an independent risk factor for vasculogenic ED.34x34Shabsigh, R, Fishman, IJ, Schum, C, and Dunn, JK. Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology. 1991; 38: 227–231
27. Haahr MK, Jensen CH, Toyserkani NM, et al. Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial. EBioMedicine 2016;5:204-10. 10.1016/j.ebiom.2016.01.024 [PMC free article] [PubMed] [CrossRef]

Treatment of ED which was previously confined to invasive procedures, cavernosal injections or to rather ineffective oral medications was revolutionized in 1999 with the introduction of the orally administered PDE5 inhibitor sildenafil. Phosphodiesterase type 5 inhibitors are the first-line therapy for ED of organic aetiology unless there is a specific contraindication to their use. This class of agents is widely used because of its effectiveness and safety.38 Interactions with cardiovascular drugs have been minimal with the exception of nitrates and other nitric oxide (NO) donors (such as nicorandil), where co-administration may result in severe vasodilation and hypotension. However, nitrates are often overused in clinical practice; therefore, the option of their discontinuation should be considered. A strong body of clinical data shows that all three agents (sildenafil, tadalafil, and vardenafil) do not increase the risk of non-fatal myocardial infarction, stroke, or cardiovascular deaths. These drugs do not exacerbate ischaemia or worsen exercise tolerance in patients with known CAD who achieve levels of exercise comparable or greater than that achieved during sexual intercourse.38,39 Phosphodiesterase type 5 is expressed throughout the human body, including the pulmonary and systemic vasculature and hypertrophied myocardium. While currently their only additional indication, beyond ED, is idiopathic pulmonary hypertension (for sildenafil and tadalafil), they show potential to be of benefit in several other conditions, such as CAD and systolic heart failure.39 Mechanisms of benefit of PDE5 inhibitors include pulmonary and systemic vasodilation, increased myocardial contractility, reduced large artery stiffness and wave reflections, improved endothelial function, and reduced apoptosis, fibrosis and hypertrophy through mechanisms involving NO, cyclic guanosine monophosphate, protein kinase G and Rho kinase.39 A very important issue is whether treatment of ED per se (and not of its risk factors and comorbidities) will have an impact on cardiovascular risk. While this applies to all therapeutic modalities of ED, it is particularly pertinent for PDE5 inhibitors, since they represent the mainstay of ED therapy. Data are limited to date. Gazzaruso et al.21 showed a trend of PDE5 inhibitors to reduce cardiovascular morbidity and mortality in diabetic patients with silent CAD and ED, while Frantzen et al.40 showed that 2 years after the introduction of sildenafil, the relative risk of the incidence of CVD among men with ED compared with healthy men significantly decreased from 1.7 to 1.1.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (53) | Google ScholarSee all References Early work in this field, performed by Masters and Johnson in 1966, involved evaluation of young patients in a laboratory setting and found that heart rates and systolic blood pressure levels during sexual activity approached levels seen during maximal exercise.84x84Stein, RA. Cardiovascular response to sexual activity. Am J Cardiol. 2000; 86: 27F–29F
Crossref | PubMed | Scopus (165) | Google ScholarSee all References Typically, the response to sexual activity is no more than an increase in heart rate to 130 beats/min and an increase in systolic blood pressure level to 170 mm Hg.51x51DeBusk, R, Drory, Y, Goldstein, I et al. Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel. Am J Cardiol. 2000; 86: 62F–68F

Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Sildenafil has a 4000-fold increased selectivity for PDE-5 over PDE-3, has negligible effects on heart rate, and has only a modest effect on blood pressure level in healthy persons, with an average systolic pressure decrease of 10 mm Hg with a single dose of 100 mg.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
Abstract | Full Text | Full Text PDF | PubMed | Scopus (66) | Google ScholarSee all References Although some case studies have reported a relationship between calcium channel blockers and ED, most studies suggest that this effect is minimal and that any relationship is likely secondary to a decrease in blood pressure with consequent reflex sympathetic activation.42x42Weiss, RJ. Effects of antihypertensive agents on sexual function. Am Fam Physician. 1991; 44: 2075–2082
PubMed | Google ScholarSee all References Unlike sildenafil, vardenafil has been associated with a slight prolongation of the QT interval and thus should not be used by patients with a congenital QT prolongation or by any patient currently taking antiarrhythmic medications.67x67Vardenafil (levitra) for erectile dysfunction. Med Lett Drugs Ther. 2003; 45: 77–78
Abstract | PubMed | Scopus (136) | Google ScholarSee all References Another study evaluated 32 hypertensive men with ED and 78 normotensive men with ED with regard to age, body mass index, hormonal profile, penile arterial flow, risk factors for arterial disease, psychiatric disease, and neurologic disease measured by pudendal nerve conduction studies.30x30Jaffe, A, Chen, Y, Kisch, ES, Fischel, B, Alon, M, and Stern, N. Erectile dysfunction in hypertensive subjects: assessment of potential determinants. Hypertension. 1996; 28: 859–862
In a prospective human phase 1 open-label and single-arm study reported by Haahr et al. (27), 17 men with refractory post radical prostatectomy ED were given a single intracavernosal injection of autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. The procedures were well-tolerated and over a 6-month follow-up period, 8 of 17 men showed improvement of their erectile function.
Abstract | PubMed | Scopus (136) | Google ScholarSee all References In a prospective review of 3250 men aged 26 to 83 years without ED at their first examination, total cholesterol and high-density lipoprotein (HDL) cholesterol levels were found to be strongly predictive of onset of ED after controlling for age, diabetes mellitus, stress level, cardiovascular disease, and prostate disease.25x25Wei, M, Macera, CA, Davis, DR, Hornung, CA, Nankin, HR, and Blair, SN. Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol. 1994; 140: 930–937
Abstract | Full Text | Full Text PDF | PubMed | Scopus (53) | Google ScholarSee all References Early work in this field, performed by Masters and Johnson in 1966, involved evaluation of young patients in a laboratory setting and found that heart rates and systolic blood pressure levels during sexual activity approached levels seen during maximal exercise.84x84Stein, RA. Cardiovascular response to sexual activity. Am J Cardiol. 2000; 86: 27F–29F

A component of the increased risk conferred by ED could be testosterone deficiency.24 Low testosterone leads to increased levels of total and LDL cholesterol, as well as to increased production of pro-inflammatory markers and mediators.25 Endothelial dysfunction and increased arterial wall thickness, stiffening, and calcification also ensue. On this basis it has been hypothesized that chronically lowered testosterone may increase CVD risk. Indeed, androgen deficiency has emerged as a predictor of CV events, as well as of all-cause and CV mortality, both in the general population and in patients with CV risk factors, with hypertension, with established CVD, and with ED.26 Viewed from the opposite angle, higher serum testosterone showed a protective role for CV events in elderly men.27 A 2010 meta-analysis limited to studies in middle-aged men found no association between total testosterone (TT) levels and CVD risk.28 However, a more recent meta-analysis involving a larger number of studies identified significant associations between androgen deficiency and increased risk of CVD and CVD mortality.29 It should be stressed, however, that the nature of these studies cannot prove causality. The possibility that low testosterone may be an epiphenomenon, marking poor general health rather than modulating CVD risk per se has to be explored.
If you have been diagnosed with heart disease or have already had a heart attack and are experiencing erectile dysfunction, it is critical that you discuss erectile dysfunction medication with your physician before considering taking it. Popular erectile dysfunction medications such as Viagra (sildenafil), Cialis (tadalafil) and Levitra (vardenafil) can interact with a range of cardiovascular disease medications. Interactions are possible with blood pressure medications; blood thinners such as Coumadin (warfarin), nitrates for the treatment of chest pain, and antiarrhythmia medication for the treatment of irregular heart rhythms.

The research is based on a Swedish national database of health records that includes all hospitals in Sweden. Researchers analyzed the records of men age 80 years or younger who were hospitalized for a first heart attack between 2007 and 2013. Tracking the men for an average of 3.3 years following this first heart attack, they compared outcomes among those who subsequently filled a prescription for a PDE5 inhibitor or alprostadil to those who did not. Overall just over 7 percent of men were prescribed an erectile dysfunction drug, 92 percent of whom were prescribed a PDE5 inhibitor and 8 percent of whom were prescribed alprostadil.


The recommended dosage of sildenafil is 50 mg/day, usually taken 1 hour before sexual activity. This dose may be increased to 100 mg or decreased to 25 mg based on side effects.6 PDE5 inhibitors also have a beneficial effect in the treatment of heart failure with reduced ejection fraction as well as pre- and post-capillary pulmonary hypertension. The use of PDE5 inhibitors in the treatment of right heart failure and left ventricular failure associated with combined pre- and post-capillary pulmonary hypertension has been well studied.71,72
Gutiérrez-González, Enrique; Castelló, Adela; Fernández-Navarro, Pablo; Castaño-Vinyals, Gemma; Llorca, Javier; Salas-Trejo, Dolores; Salcedo-Bellido, Inmaculada; Aragonés, Nuria; Fernández-Tardón, Guillermo; Alguacil, Juan; Gracia-Lavedan, Esther; García-Esquinas, Esther; Gómez-Acebo, Inés; Amiano, Pilar; Romaguera, Dora; Kogevinas, Manolis; Pollán, Marina; Pérez-Gómez, Beatriz. “Dietary Zinc and Risk of Prostate Cancer in Spain: MCC-Spain Study.” Nutrients. Jan 2019, 11(1).
In most men, ED is recognised as sharing vascular aetiology with IHD.17 ED and IHD share common risk factors, such as hypertension, hyperlipidaemia, diabetes, obesity, lack of physical exercise, cigarette smoking, poor diet, excess alcohol consumption and psychological stress, including depression.30 Endothelial dysfunction has been implicated as a common mechanism between CAD and ED and it has an important role in the development of atherosclerosis.31
Before a man concludes that oral drugs don’t work for him, he should have his testosterone levels checked to rule out hormone deficiency as the cause of (or as a contributor to) his sexual dysfunction. Other symptoms of low testosterone include a low sex drive and infertility. Checking testosterone levels requires a blood test. If a man’s levels of testosterone are decreased or at the lower end of normal, his doctor may prescribe supplemental testosterone therapy, either as testosterone injections or testosterone gel, which is applied daily to the skin. In some cases, testosterone therapy alone can resolve sexual dysfunction, or it can be combined with the use of oral erectile dysfunction drugs.
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