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Objectives Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. Methods This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. Results In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). Conclusions This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed anti-hypertensives with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated the potential association between the use of ACEIs and/or ARBs and the development of lung cancer in a large population using propensity matching. Methods: This was a population-based cohort study in a large healthcare system in three regions of the US. All adult patients who entered the Mayo Clinic health system from January 1, 2000 to April 30, 2018 with at least one year of follow-up were included. Pairwise propensity score matching was performed using demographics and comorbidities. Findings: 3,253,811 patients with median age of 59 (range 18-103) years old were included. The ACEI group had a higher freedom from lung cancer versus controls at 5, 10, and 15 years [15 year: 98.47% (CI95: 98.41%-98.54%) vs. 98.26% (CI95: 98.20%-98.33%)] while ARB had similar rates versus controls at all time points. For patients diagnosed with lung cancer, median all-cause survival was significantly higher in the ACEI [34.7 months (CI 95: 32.8-36.6)] and ARB (30.9 months (CI95: 28.1-33.8)] groups than the control group (20.6 months (CI95: 20.1-21.1). Interpretation: This is the largest analysis of lung cancer risk with ACEI and ARBs using patient data from three regions of the United States. This study demonstrates a decreased risk of lung cancer with ACEI use, no difference in risk with ARBs, and no difference in the lung cancer subtypes with ACEI or ARB usage versus controls using propensity score matching. Additionally, ACEI and ARB use was found to be associated with increased survival in those diagnosed with lung cancer. This study supports the continued use of ACEIs without concern for increasing the risk of lung cancer. Funding Statement: Grant Number UL1 TR000135 from the NIH Clinical and Translational Award for the search engine and not awarded to any authors. Declaration of Interests: All authors (SH, MW, RB, YD, AL, CB, ZL, PJ, and NP) report no conflict of interest. Ethics Approval Statement: The Mayo Clinic Institutional Review Board approved this study

Summary Background and objectives Whether chronic kidney disease (CKD) should also be considered a coronary disease equivalent like diabetes is not clear. Design, setting, participants, & methods Veterans with and without diabetes and with and without CKD were prospectively recruited. A competing Cox regression model was used to describe the risk of myocardial infarction (MI) in the two groups (CKD and diabetes) over a decade of follow-up. Results The incidence rate of MI in those without CKD was 0.047/yr and in those with CKD was 0.206/yr. Multivariate adjustment revealed the incident rate ratio for MI in CKD as 3.5 and for diabetes mellitus as 2.5. The cumulative incidence for MI was influenced by CKD and diabetes. CKD was associated with a subhazard ratio for MI of 3.74; in contrast, diabetes was associated with a subhazard ratio for MI of 2.6. For the outcome of all-cause mortality, after multivariate adjustment, CKD was associated with a hazard ratio (HR) of 1.86, which was similar to the HR of 2.27 for prevalent coronary artery disease. The HR for diabetes was NS at 1.35. Conclusions CKD is associated with a risk of death similar to that of established coronary artery disease and higher than that of diabetes mellitus. CKD is associated with a risk of MI that is at least as much as that from diabetes mellitus. Among veterans, CKD appears to be a coronary disease equivalent.

Background. Patients with diabetes mellitus (DM) with chronic kidney disease (CKD) often have no proteinuria. Methods. To compare the characteristics that differ between DM 1 CKD patients with and without proteinuria, we conducted a cross-sectional study followed by surveillance over a decade for ‘hard’ cardiovascular, renal and retinal outcomes. Groups were stratified by presence (n ¼ 129) and absence (n ¼ 284) of DM. Each stratum had three groups: no CKD, CKD without proteinuria and CKD with proteinuria. Results. Compared to DM 1 CKD 1 proteinuria patients, those with DM 1 CKD but without proteinuria had similar clinical characteristics including estimated glomerular filtration rate. However, they had lower 24-h ambulatory systolic and diastolic blood pressure. Crude all-cause mortality rates per 1000 patient-years in the nondiabetic group with no CKD, CKD with no proteinuria and CKD with overt proteinuria were 29.3, 68.5 and 111.1, respectively. Respective rates in the diabetic group were 50.1, 105.7 and 136.8. Diabetes increased the risk of coronary (P ¼ 0.01) and end-stage renal disease (ESRD) events (P ¼ 0.05) even after multivariate adjustments. Proteinuria aggravated the risk of cardiovascular events, ESRD, death and time to first of these events similarly among diabetics with CKD compared to nondiabetics with CKD. Diabetic patients with CKD but no overt proteinuria were much more likely than nondiabetics to progress to overt proteinuria [adjusted hazard ratio 5.28 (95% confidence interval 1.64–17.02), P < 0.01). CKD was a risk factor for prevalent retinopathy and proteinuria was a risk factor for incident diabetic retinopathy. Conclusions. To protect sight, those with proteinuria and DM need regular retinal examinations. Since diabetic CKD patients without proteinuria are more likely to develop overt proteinuria, close follow-up and risk factor management among these patients appear to be more important than among nondiabetic patients with CKD and no proteinuria.