Renin angiotensin system inhibitors may attenuate low LDL cholesterol-related cancer risk in type 2 diabetes

Background: In type 2 diabetes (T2D), copresence of low-density lipoprotein cholesterol (LDL-C) <2.8mmol/L with triglyceride <1.7mmol/L or with albuminuria synergistically increased cancer risk. We tested whether use of renin angiotensin system inhibitors attenuated the increased cancer risk associated with these two risk subphenotypes. Methods: A prospective cohort of 4307 patients with T2D enrolled from December 1996 to January 2005 was analysed using a new user cohort design. Cox model analysis was used to obtain hazard ratios and 95% confidence intervals. The study measured additive interactions between nonuse of renin angiotensin system inhibitors and low LDL-C plus low triglyceride or albuminuria for the risk of cancer. A positive interaction suggests a specific drug effect on the low LDL-C-related cancer risk. Results: During 18769 person years of follow-up (median follow-up years: 4.44), 4.48% (n=193) of patients developed cancer. Use of renin angiotensin system inhibitors was associated with reduced cancer risk among patients with copresence of low LDL-C plus low triglyceride or low LDL-C plus albuminuria but not in patients without these subphenotypes. In multivariable analysis, renin angiotensin system inhibitor usage attenuated the hazard ratio of copresence of low LDL-C plus low triglyceride versus lack of this subphenotype for cancer from 2.08 (95% CI: 1.25-3.47) to 1.13 (0.61-2.11) with significant additive interaction (p=0.0225). Similarly, RAS inhibitor usage attenuated the hazard ratio of copresence of low LDL-C plus albuminuria versus lack of this subphenotype for cancer from 1.99 (95% CI: 1.12-3.56) to 0.82 (0.43-1.54) with significant additive interaction (p=0.0009). Conclusion: In T2D, renin angiotensin system inhibitor usage may specifically attenuate the low LDL-C-related cancer risk.