People with diabetes, a condition characterised by high blood sugar levels, are more likely to develop heart disease, which also leads to death. Men with diabetes are also more likely to develop erectile dysfunction (ED) commonly known as impotence, which is well known to cause heart disease. The relationship between ED and heart disease is so strong that it has been proposed that both diseases are different manifestations of the same disease. Given that people with diabetes have a higher risk of heart disease than those without diabetes, it would be reasonable to say that people with ED are more likely to develop heart disease and die when they have diabetes than when they do not have diabetes. However, recent evidence seems to suggest that the relationship between ED and heart disease is similar in people with and without diabetes. No study has actually directly compared the relationship in people with and without diabetes, so it is difficult to know. Using available information, we will study if people with ED are more likely to develop heart disease and die when they have diabetes than when they do not have diabetes. The findings from this study could provide more information on whether people who have ED with no diabetes should be treated as if they had both ED and diabetes. There are medications that can reduce the chances of developing heart disease irrespective of whether one has diabetes or not.
It is uncertain if ED confers an excess risk of cardiovascular disease (CVD) and mortality in patients with T2D compared with no T2D. Using CPRD data linked to Hospital Episode Statistics Admitted Patient Care (HES APC) and Office for National Statistics (ONS) mortality data, the study will investigate if the presence of ED confers an excess risk of adverse cardiovascular outcomes in patients with T2D compared with those without T2D. A retrospective cohort study design will be used for the analysis. Cox regression analysis will be used to model the associations of ED (exposure defined using medical codes or medication history (Avanafil, Sildenafil, Tadalafil, Vardenafil) to 3-point major adverse cardiovascular events (MACE) defined as nonfatal stroke, nonfatal myocardial infarction and cardiovascular death.
Adjustment for key confounders such as age, sex, ethnicity, smoking, body mass index, comorbidities (such as depression and hypertension), and medications (Anti-hypertensives such as: ACE inhibitors, angiotensin-2 receptor blockers (ARBs), calcium channel blockers, diuretics, beta-blockers; Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) and other categories of antidepressants; Diabetic drugs such as: Metformin, Sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists) and the inclusion of an interaction term to explore whether the effect of ED is modified by T2D status.
Using interaction analyses, we will also assess for evidence of effect modification by important characteristics such as age, body mass index, and ethnicity. There is potentially significant public health benefit. ED at the population level is understudied, and how T2D interacts with ED, which leads to the development of cardiovascular disease, has not been elucidated. Therefore, our study may provide a significant opportunity for creating public health interventions to identify and intervene earlier for preventative treatment for patients with ED.
Primary (cardiovascular) outcomes: 3-point MACE (major adverse cardiovascular events) defined as nonfatal stroke, nonfatal myocardial infarction and cardiovascular death.
Secondary outcomes: other cardiovascular endpoints and all-cause death.
Mohammad Ali - Chief Investigator - University of Leicester
- Corresponding Applicant -
Clare Gillies - Collaborator - University of Leicester
Francesco Zaccardi - Collaborator - University of Leicester
Kamlesh Khunti - Collaborator - University of Leicester
Setor Kunutsor - Collaborator - University of Leicester
Sharmin Shabnam - Collaborator - University of Leicester
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation