The incidence of cancer deaths among hypertensive patients in a large Chinese population: A cohort study

Wong, Martin C. S.; Tam, Wilson W.S.; Lao, Xiang Qian; Wang, Haoxiang; Kwan, Mei Po; Cheung, Clement S.K.; Tong, Ellen L.H.; Cheung, Ngai Tseung; Griffiths, Siân; Coats, Andrew J.S.

doi:10.1016/j.ijcard.2014.10.028

Cited by 17 publications

(12 citation statements)

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“…49 CCBs also have been associated with decreased survival in certain cancers when compared with β-blockers. 50 Deaths were also increased with CCBs use in patients with breast cancer; in contrast, CCBs use was associated with improved survival in lung cancer patients. 25 To resolve this discrepancy in lung cancer and breast cancer outcomes, this study demonstrates the potential mechanisms of CCB association with improved survival in lung cancer patients.…”

Section: Discussionmentioning

confidence: 98%

<p>Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells via Autophagy and Apoptosis</p>

Wong¹,

Chiu

et al. 2020

CMAR

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Hypertension and cancer are frequently found comorbidity occurring in same individual. This study was intended to evaluate the anticancer effects of commonly used antihypertensive medications and chemotherapy on chemoresistant lung cancer cells. Methods: Calcium channel blockers (CCBs), including Verapamil, Diltiazem, and Nifedipine, either alone or combined with docetaxel (DOC) or vincristine (VCR) were used to treat A549 lung adenocarcinoma chemoresistant sublines. Cell viability was determined by MTT assay, and colony formation assay was used to demonstrate the long-term effect of CCBs on proliferation of the sublines. Apoptosis was evaluated by Annexin V assay and autophagy intensity was quantitated from acidic vesicular organelle formation. Pan-caspase inhibitor, shATG5 interference and chloroquine were applied to study the roles of Verapamil on apoptosis and autophagy, with related proteins verified by Western blot analysis. Results: Results show that 10 μM of Verapamil and Diltiazem, but not Nifedipine, differentially induce autophagy in DOC-resistant or VCR-resistant A549 cells, respectively. When CCBs are combined with DOC or VCR to treat the sublines, 10 μM of Verapamil induces autophagy more significantly than Diltiazem and Nifedipine, respectively, in DOC-resistant (54.91±0.76, 18.03±0.69, 7.05±0.30) or VCR-resistant A549 (32.41±1.04, 21.51±0.63, 7.14 ±0.24) cells. Inhibition of apoptosis by pan-caspase inhibitor partly reduced cell death indicates association of caspase-dependent cell death but with persistence of autophagy. Inhibition of autophagy by interfering ATG5 expression reduced c-PARP level and apoptotic cells suggest a pro-death role of autophagy. Chloroquine treatment enhanced autophagosome accumulation and cell death but with reduced c-PARP level suggests that mechanism of caspase-independent cell death also contributes to Verapamil/chemotherapy-induced anticancer effects. Conclusion: Verapamil combined with DOC or VCR induces chemoresistant lung cancer cells to death through autophagy burst and apoptosis more strongly than Diltiazem and Nifedipine. Administering Verapamil or Diltiazem individually with chemotherapy, but not Nifedipine, can be considered in lung cancer patients with hypertension.

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Section: Discussionmentioning

confidence: 98%

<p>Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells via Autophagy and Apoptosis</p>

Wong¹,

Chiu

et al. 2020

CMAR

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“…Three studies were also excluded as their reported data were not restricted to prediagnosis or postdiagnosis (Ganz et al, 2011;Engineer et al, 2013;Grytli et al, 2013). We further excluded four studies (Fletcher et al, 1993;Shah et al, 2011;Springate et al, 2015;Wong et al, 2015) that compared the effect of β blockers with that of other antihypertensive medications. Finally, 20 cohort studies (Hole et al, 1993;Powe et al, 2010;Barron et al, 2011;Lemeshow et al, 2011;Melhem-Bertrandt et al, 2011;Diaz et al, 2012;Yusuf et al, 2012;Aydiner et al, 2013;Botteri et al, 2013;Holmes et al, 2013aHolmes et al, , 2013bJohannesdottir et al, 2013;Livingstone et al, 2013;Wang et al, 2013;Assayag et al, 2014;Cata et al, 2014;Chae et al, 2014;De Giorgi et al, 2014;Grytli et al, 2014;Jansen et al, 2014) and four case-control studies Hicks et al, 2013;McCourt et al, 2014) involving 76 538 participants were selected for metaanalysis.…”

Section: Resultsmentioning

confidence: 99%

β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies

Zhong

Yu²,

Zhang³

et al. 2016

European Journal of Cancer Prevention

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A number of epidemiologic studies have attempted to link the use of β blockers to mortality in cancer patients, but their findings have been inconclusive. A meta-analysis was carried out to derive a more precise estimation. Relevant studies were identified by searching PubMed and EMBASE to May 2015. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. Twenty cohort studies and four case-control studies involving 76 538 participants were included. The overall results showed that patients who used β blockers after diagnosis had an HR of 0.89 (95% CI 0.81-0.98) for all-cause mortality compared with nonusers. Those who used β blockers after diagnosis (vs. nonusers) had an HR of 0.89 (95% CI 0.79-0.99) for cancer-specific mortality. Prediagnostic use of β blockers showed no beneficial effect on all-cause mortality or cancer-specific mortality. Stratifying by cancer type, only breast cancer patients who used β blockers after diagnosis had a prolonged overall survival. A linear but nonsignificant trend was found between postdiagnostic β-blocker use and mortality of cancer patients. In conclusion, the average effect of β-blocker use after diagnosis but not before diagnosis is beneficial for the survival of cancer patients.

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“…However, Jan et al found that CCBs enhanced apoptosis of prostate cancer cells and might have a protective effect on prostate cancer (5). Some studies showed that CCB usage significantly increased cancer mortality (18,19), while other studies did not find this relationship (14). To obtain further data on the possible influence of CCBs usage on cancer outcomes, we conducted an observational study with 2415 patients who underwent esophagectomy from 2009 to 2013 with data in the Sun Yet-Sen University Cancer Center Database.…”

Section: Introductionmentioning

confidence: 99%

The impact of preoperative use of calcium channel blockers on outcomes of patients undergoing esophagectomy: a propensity score-matched cohort study

Lin¹,

Zhang²,

Wu³

et al. 2020

Preprint

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BACKGROUND In this study, we compared the effects of using preoperative CCBs on perioperative outcomes, cancer recurrence and overall survival in patients undergoing esophagectomy. METHODS A retrospective cohort study was performed on patients who underwent esophagectomy at the Sun Yat-Sen University Cancer Center (n=2415, 2009-2013). Univariate and multivariate logistic regression analyses were performed to assess the perioperative outcomes, while recurrence-free survival and overall survival were assessed using Kaplan-Meier survival estimates and compared using a multivariate Cox proportional hazards regression, adjusted with propensity scores. RESULTS There were 162 patients in the CCB group and 1110 patients in the non-CCB group and the total incidence of perioperative complications was 45.7% in the CCB group and 42.5% in the non-CCB group. The differences in total perioperative complications and other perioperative outcomes were not significantly different between the two groups (P>0.05). The mortality rate was not significantly different between the two groups after matching (38.1% vs 31.6%, P=0.233). The difference in recurrence rate between the two groups was not statistically significant after matching (43.2% vs 32.9%, P = 0.061). Overall survival was shorter in patients with preoperative CCB use than in patients without CCB use (hazards ratio: 1.517, 95% confidence intervals (CI): 1.036-2.220, P=0.030). The multivariate Cox proportional hazards regression adjusted with propensity scores found that a history of smoking cigarettes, clinical stage III at diagnosis, preoperative CCB use, preoperative diuretics use, operation type and postoperative chemotherapy affected the overall survival of patients after esophagectomy. Recurrence-free survival was similar between the CCB and non-CCB groups (HR: 1.425, 95%CI: 0.989-2.053, P=0.054). A history of chronic lung disease, hypertension, and preoperative use of beta-blockers affected the recurrence-free survival of patients after esophagectomy. CONCLUSION Preoperative CCBs use was associated with shorter overall survival but did not affect recurrence-free survival or the postoperative complications for patients undergoing esophagectomy.

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The incidence of cancer deaths among hypertensive patients in a large Chinese population: A cohort study

Cited by 17 publications

References 50 publications

<p>Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells via Autophagy and Apoptosis</p>

<p>Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells via Autophagy and Apoptosis</p>

β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies

The impact of preoperative use of calcium channel blockers on outcomes of patients undergoing esophagectomy: a propensity score-matched cohort study

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