Abstract
Several studies have indicated that the use of antihypertensive medications may influence the incidence of bladder/kidney cancer, with some scholars refuting any such association. Hence, a systematic review is needed to verify this linkage. we comprehensively searched PubMed, Embase, Web of Science, and the Cochrane Library for original studies reporting a relationship between antihypertensive medications and risk of bladder/kidney cancer. We included 31 articles comprising 3,352,264 participants. We found a significant association between the risk of kidney cancer and any antihypertensive medications use (relative risk (RR) = 1.45, 95% CI 1.20-1.75), as well as angiotensin-converting enzyme inhibitors (RR = 1.24, 95% CI 1.04-1.48), angiotensin II receptor blockers (ARB) (RR = 1.29, 95% CI:1.22-1.37), beta-blockers (RR = 1.36, 95% CI 1.11-1.66), calcium-channel blockers (RR = 1.65, 95% CI 1.54-1.78) and diuretics (RR = 1.34, 95% CI 1.19-1.51). In case of bladder cancer, a statistical significance was observed with the use of ARB (RR = 1.07, 95% CI 1.03-1.11) but not with the other antihypertensive medications. There was a linear association between the duration of antihypertensive medications and the risk of kidney cancer (P = 0.061 for a non-linear trend) and the pooled RR for the per year increase in antihypertensive medications duration of use was 1.02 (95% CI: 1.01-1.02). Our results indicate that there is a significant association between each class of antihypertensive medications and the risk of kidney cancer, and this trend presented as a positive linear association. Furthermore, the use of ARB has been linked to the risk of bladder cancer.
Highlights
Hypertension is a highly prevalent chronic disease worldwide in the elderly, necessitating the long-term use of various antihypertensive medications to prevent cardiovascular morbidity and mortality
We found a significant association between the risk of kidney cancer and any antihypertensive medications use (relative risk (RR) = 1.45, 95% confidence intervals (CI) 1.20-1.75), as well as angiotensin-converting enzyme inhibitors (RR = 1.24, 95% CI 1.04-1.48), angiotensin II receptor blockers (ARB) (RR = 1.29, 95% CI:1.22-1.37), beta-blockers (RR = 1.36, 95% CI 1.11-1.66), calcium-channel blockers (RR = 1.65, 95% CI 1.54-1.78) and diuretics (RR = 1.34, 95% CI 1.19-1.51)
31 articles www.aging-us.com met the inclusion criteria and were included in this meta-analysis [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47]. This selection consisted of 18 articles designed as case-control studies and 13 articles designed as cohort studies, with approximately 3,352,264 participants. These articles were regarded as independent studies since the role of antihypertensive medications in the risk of bladder/kidney cancer was assessed according to the different antihypertensive medications classes (ACEI, ARB, BB, calcium-channel blockers (CCB), diuretics or any antihypertensive medications), cancer sites, and gender
Summary
Hypertension is a highly prevalent chronic disease worldwide in the elderly, necessitating the long-term use of various antihypertensive medications to prevent cardiovascular morbidity and mortality. Several studies have demonstrated the potential risks of antihypertensive medications including orthostatic hypotension, falls, cognitive decline, dementia, fractures, diabetes, and cancer [1]. Preclinical experimental studies have indicated that antihypertensive medications, such as angiotensinconverting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), calcium-channel blockers (CCB) and beta-blockers (BB), can facilitate or interfere with tumor cell proliferation, migration, and apoptosis, as well as angiogenesis [2,3,4]. It was observed that angiotensin II type I receptor (Ang II AT1R) was highly expressed in bladder cancer cells of high-stage and/or high-grade tumors and Ang II AT1R www.aging-us.com signaling could induce the expression of the vascular endothelial growth factor (VEGF) [5]. ACEIs and ARBs have demonstrated anti-angiogenetic effects, reducing VEGF expression in bladder malignancies [4]. The thiazide diuretic treatment in rats could result in degenerative changes including cell apoptosis and tumor cell markers in the distal tubule [7]
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