Effects Of Calcium Channel Blockers Research Articles

Utilizing genetics and proteomics to assess the role of antihypertensive drugs in human longevity and the underlying pathways: a Mendelian randomization study.

Antihypertensive drugs are known to lower cardiovascular mortality, but the role of different types of antihypertensive drugs in lifespan has not been clarified. Moreover, the underlying mechanisms remain unclear. To minimize confounding, we used Mendelian randomization to assess the role of different antihypertensive drug classes in longevity and examined the pathways via proteins. Genetic variants associated with systolic blood pressure (SBP) corresponding to drug target genes were used as genetic instruments. The genetic associations with lifespan were obtained from a large genome-wide association study including 1 million European participants from UK Biobank and LifeGen. For significant antihypertensive drug classes, we performed sex-specific analysis, drug-target analysis and colocalization. To examine the mediation pathways, we assessed the associations of 2291 plasma proteins with lifespan, and examined the associations of drug classes with the proteins affecting lifespan. After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs) and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78 to 3.28 per 5-mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47 to 5.33, and vasodilators: 2.92, 95% CI 1.08 to 4.77). The beneficial effects of BBs and CCBs were more obvious in men. ADRB1, CACNA2D2, CACNB3, CPT1A, CPT2, and EDNRA genes were related to extended lifespan with CPT2 further supported by colocalization evidence. 86 proteins were related to lifespan, of which 4 proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan. BBs, CCBs and vasodilators may prolong lifespan, with potential sex differences for BBs and CCBs. The role of CCBs in lifespan is partly mediated by CDH1. Prioritizing the potential protein targets can provide new insights into healthy aging.

Evaluating calcium channel blockers and bisphosphonates as otoprotective agents in cochlear implantation hearing preservation candidates

Objectives: Evaluate potential effects of calcium channel blockers (CCB) and bisphosphonates (BP) on residual hearing following cochlear implantation. Methods: Medications of 303 adult hearing preservation (HP) candidates (low frequency pure tone average [LFPTA] of 125, 250, and 500 Hz ≤80 dB HL) were reviewed. Postimplantation LFPTA of patients taking CCBs and BPs were compared to controls matched by age and preimplantation LFPTA. Results: Twenty-six HP candidates were taking a CCB (N = 14) or bisphosphonate (N = 12) at implantation. Median follow-up was 1.37 years (range 0.22–4.64y). Among subjects with initial HP, 29% (N = 2 of 7) CCB users compared to 50% (N = 2 of 4) controls subsequently lost residual hearing 3–6 months later (OR = 0.40, 95% CI = 0.04–4.32, p = 0.58). None of the four BP patients with initial HP experienced delayed loss compared to 50% (N = 2 of 4) controls with initial HP (OR = 0.00, 95% CI = 0.00–1.95, P = 0.43). Two CCB and one BP patients improved to a LFPTA <80 dB HL following initial unaided thresholds that suggested loss of residual hearing. Discussion: There were no significant differences in the odds of delayed loss of residual hearing with CCBs or BPs. Conclusion: Further investigation into potential otoprotective adjuvants for maintaining residual hearing following initial successful hearing preservation is warranted, with larger cohorts and additional CCB/BP agents.

The Effect of Calcium Channel Blockers on Vascular Remodeling and Intra-Renal Hemodynamics in Chronic Kidney Disease

The Effect of Calcium Channel Blockers on Vascular Remodeling and Intra-Renal Hemodynamics in Chronic Kidney Disease

Causal relationship between genetic proxies for calcium channel blockers and the risk of depression: a drug-target Mendelian randomization study.

Calcium channel blockers (CCBs) are widely used in the clinical management of hypertension. Depression, a common comorbidity of hypertension, is an important issue in the management of hypertension. However, the impact of CCBs on depression risk remains controversial. We aim to investigate the causal effect of CCBs on depression through drug-target Mendelian randomization (MR) analysis. To proxy CCBs, we utilized the genetic variations located in or around drug target genes that were related to systolic blood pressure (SBP). Coronary artery disease (CAD) served as the positive control outcome. Genetic summary data of SBP, CAD, and depression were obtained from genome-wide association studies (GWAS) based on European population. Inverse variance weighted (IVW) method was applied as the main analysis to estimate the causal effect. Cochran's Q test, MR-Egger intercept, MR pleiotropy residual sum and outlier (MR-PRESSO) and leave-one-out sensitivity analysis were used to test the robustness of the results. Meta-analysis was applied to further confirm whether causal relationships existed between CCBs and depression. The IVW results failed to reveal any causal relationship between genetic proxies for CCBs and depression (P > 0.05). Cochran's Q test showed no evidence of heterogeneity (P > 0.05). The MR-Egger intercept test suggested no evidence of directional pleiotropy, and the MR pleiotropy residual sum and outlier (MR-PRESSO) global test for horizontal pleiotropy was also not significant (P > 0.05). Leave-one-out analysis did not reveal any genetic variant that influenced the results. In addition, the meta-analysis further confirmed the absence of a causal relationship. The present study indicates no association of genetic proxies for CCBs with depression. Further studies are necessary to provide definitive evidence.

Effects of calcium channel blockers on perioperative ischemic events in hypertensive patients with intracranial aneurysms undergoing neurointervention

BackgroundAlthough calcium channel blockers (CCBs) are useful in stroke prevention, their specific role in preventing stroke in hypertensive patients with intracranial aneurysms undergoing endovascular stent placement remains unclear.MethodsWe retrospectively examined...

O93: Calcium channel blockers are associated with improved survival in pancreatic cancer patients undergoing neoadjuvant chemotherapy and resection

Abstract Background Repurposing existing drugs for use in oncology is more safe, efficient and cost-effective than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance and many of the hallmarks of cancer. This study aims to assess the impact of calcium channel blockers (CCB) in pancreatic cancer. Methods Retrospective population study including patients in the SEER-Medicare linked database who underwent resection with curative intent of pancreatic ductal adenocarcinoma diagnosed between 2007 and 2017. Adjusted cox regression models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, we assessed the impact of CCB separately in patients receiving chemotherapy. Results 6,223 patients were included, of whom 660 were prescribed CCB. 591 patients received neoadjuvant chemotherapy prior to resection; in this cohort CCB prescription was associated with a significant improvement in overall survival when adjusting for multiple prognostic factors (aHR=0.715, 0.514-0.996, P=0.047). This effect was not observed in patients who did not receive neoadjuvant chemotherapy (aHR=1.082, 0.982-1.191, P=0.112), or in the overall cohort (aHR=1.056, 0.963-1.158, P=0.248), suggesting a chemosensitising effect. Discussion CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy. This indicates a chemosensitising effect of CCB, which mirrors previous laboratory studies. This study defines those receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer.

The Effects of Calcium Channel Blocker Combined with Oxaliplatin on Apoptosis of Bladder Cancer Cells

Objective: This experiment explores the effect of calcium ion (Ca2+) on oxaliplatin-induced bladder cancer cell apoptosis and investigates the impact of blocking calcium channels on oxaliplatin-induced bladder cancer cell apoptosis.

Atorvastatin as an Antihypertensive Agent: A Pilot Study.

Objective Hypertension (HTN) is among the most common causes of chronic disease burden, along with dyslipidemia. It is a prominent risk factor for cardiovascular and cerebrovascular morbidity and mortality. More often than not, HTN coexists with dyslipidemia. This study aimed to see the antihypertensive effect of statins (atorvastatin), as certain animal models have shown that statins have a voltage-gated calcium channel-blocking effect. Material and methods Thiswas a randomized controlled trial done at the Ayub Hospital Complex in Abbottabad, Pakistan. After ethical approval, 120 patients with newly diagnosed hypertension belonging to either gender and aged 35 and above were enrolled in the trial. They were randomly divided into two groups, with each group comprising 60 patients. One group was administered amlodipine 5 mg per oral (PO) once a day, while the other group was given 5 mg of amlodipine PO plus 10 mg of atorvastatin PO. The patients were examined on a follow-up visit 14 days later, and blood pressure was recorded as per protocols. Results A total of 120 newly diagnosed patients were studied in this trial. The mean age was 51.07 years, with a standard deviation of ±6.15 years and a range of 41-60 years. There were 64 (53.3%) males and 56 (46.7%) females in the study. The mean systolic blood pressures (SBPs) and diastolic blood pressures (DBPs) in Group 2 (amlodipine 5 mg + atorvastatin 10 mg) were significantly lower than the patients in Group 1 (only amlodipine 5 mg) in the follow-up visit, which was 14 days after starting the medication (p≤0.05). Conclusion The addition of a lipid-lowering drug to an antihypertensive regimen results in a better lowering of blood pressure in hypertensive individuals.

Abstract 13555: Effect of Calcium Channel Blockers on Clinical Outcomes in Patients After Percutaneous Coronary Intervention With Left Ventricular Dysfunction

Although calcium channel blockers (CCBs) are effective in hypertension and IHD, short-acting CCBs are not recommended for heart failure due to have negative inotropic effects. On the other hand, long-acting CCBs have been reported to be safe for use in patients with cardiac dysfunction, but details are still unclear. In this study, we investigated the relationship between the effects of CCBs on CAD patients and left LV function. Methods: We enrolled 7173 consecutive CAD patients (Age; 69 [61-76] years and male; 78%) who underwent successful PCI for AP or ACS between April 2008 and March 2020 from prospective, multicenter registry (FUJISUN registry). Of the enrolled patients, 5307 analyzable patients were divided by LVEF &lt;40 or ≥40%. Patients were prospectively followed for a maximum of 8 years or until the occurrence of the cardiac events (CEs): cardiac death, nonfatal MI. Results: During the follow-up period (3.6 [1.4-6.7] years), 230 (4%) CEs occurred (109 Cardiac death, 121 MI). Both patients with LVEF &lt;40% and ≥40% had higher prevalence of HT and lower levels of BNP in CCB group than in non-CCB group. Propensity match analysis was performed to reduced selection bias for CCB use in each group. In patients with LVEF &lt;40%, Kaplan-Meier analysis showed that CCB group had significantly lower probability of CEs than non-CCB group, whereas in those with LVEF ≥40%, the probability of CE was similar in both groups. Multivariate Cox proportional hazards analysis showed that CCB group had significantly lower probabilities of CEs compared with non-CCB group in patients with LVEF&lt;40%, (HR 0.25; 95% CI 0.09-0.71, p &lt;0.01), but not in those with LVEF≥40% (HR 1.13; 95% CI 0.80-1.60, p = 0.50). Conclusions: Long-acting CCBs may improve clinical outcomes in post-PCI CAD patients with LV dysfunction.

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH. Genetic instruments and outcome data were obtained from independent genome-wide association studies (GWAS) or published data, which were exclusively restricted to European ancestry. Causal relationships were identified using inverse-variance weighted MR analyses and a series of statistical sensitivity analyses. The FinnGen consortium was used for repeated analysis to verify results obtained from the above GWAS. Two-sample MR analysis showed that genetically determined Systolic BP, Dystolic BP, and Pulse Pressure were related to a higher risk of IA and SAH. Based on identified single nucleotide polymorphisms (SNPs) that influence the effect of calcium channel blockers (CCB, 42 SNPs), beta-blockers (BB, 8 SNPs), angiotensin-converting enzyme inhibitors (ACEI, 2 SNPs), angiotensin receptor blockers (ARB, 1 SNPs), and thiazides (5 SNPs), genetically determined effect of CCBs was associated with a higher risk of IA (OR, 1.07 [95% CI, 1.03-1.10], p = 5.02 × 10-5) and SAH (OR, 1.06 [95% CI, 1.03-1.09], p = 1.84 × 10-3). No associations were found between other antihypertensive drugs and the risk of IA or SAH. The effect of CCBs on SAH was confirmed in FinnGenconsortium samples (OR, 1.04 [95% CI, 1.00-1.08], p = 0.042). This MR analysis supports the role of elevated blood pressure in the occurrence of intracranial aneurysms and subarachnoid hemorrhage. However, genetic proxies for calcium channel blockers were associated with an increased risk of intracranial aneurysms and subarachnoid hemorrhage. Further studies are required to confirm these findings and investigate the underlying mechanisms.

Clinical Association of Achilles Tendinopathy and Hypertension Mediated by CaV1.2 Voltage-gated Ca2+ Channel

Category: Basic Sciences/Biologics; Hindfoot Introduction/Purpose: The Achilles tendon is subject to acute- and overuse-injuries, which may result in degenerative tendinopathy. Achilles tendinopathy is associated with pain, disability, and functional limitations. While some patients benefit from therapy and conservative measures, many progress to operative intervention. The pathogenic mechanisms of Achilles tendinopathy are largely unknown. Using novel transgenic mouse models with CaV1.2 (a voltage gated calcium channel) wildtype or a gain-of-function mutant channel, we observed potent regulatory effects of increased Ca2+ influx through CaV1.2 on Achilles tendinopathy development. CaV1.2 expression and activity has also been shown to contribute to hypertension amongst other systemic disease. We hypothesized that aberrant CaV1.2 function is a common pathogenic mechanism both hypertension and Achilles tendinopathy. To test this hypothesis, we performed an association study between two diseases. Methods: A case-control study was performed to investigate the association between Achilles tendinopathy and hypertension using TriNetX mulit-center clinical database. We identified Achilles tendinopathy and hypertension patients based on their ICD-10 codes. Chi-squared test, odds ratio (OR) and 95% confidence interval (CI) were used to detect the correlation between these two diseases. To elucidate the role of CaV1.2 in the association of Achilles tendinopathy and hypertension, we performed a retrospective cohort study with the exposure cohort defined as all subjects with hypertension and a calcium channel blocker (CCB) prescription preceding a diagnosed tendinopathy from January 1, 2011 to December 31, 2015. A matched cohort was defined as the subjects with hypertension but on medications other than CCBs. A 7-year follow-up was obtained for the outcome Achilles tendinopathy. Relative risk (RR) and hazard ratio (HR) were used to detect the effect of CCBs and other anti- hypertensives on the development of tendinopathy. Results: We determined that hypertension is more prevalent in patients with Achilles tendinopathy (42.4%) compared to those without (12.6%). The incidence of Achilles tendinopathy is significantly correlated with hypertension (p &lt; 0.0001; OR=3.17, 95%CI=3.11-3.22). Furthermore, hypertension patients on CCBs had a 28% decrease in Achilles tendinopathy risk when compared with hypertensive patients on medications other than CCBs (RR=0.72, 95%CI=0.60-0.86, p&lt; 0.0001). A cox proportional hazards model corroborated the findings, with hypertensive patients on CCBs having 26% decreased incidence of Achilles tendinopathy than patients on other medications (HR=0.74, 95%CI=0.62-0.88, p&lt; 0.0001). In contrast, we found no significant effect of angiotensin-converting enzyme inhibitors (no direct effect on Calcium channel activity) on the incidence of Achilles tendinopathy (HR=0.99, 95%CI=0.88-1.10, p=0.8273). Conclusion: There may be a correlation between Achilles tendinopathy and other common systemic diseases such as hypertension, as well as potential treatment pathways. Our study of the TriNetX clinical database provides evidence that CaV1.2 expression/activity is a potential molecular mechanism underlying Achilles tendinopathy. Additionally, an effect of CCBs in hypertensive patients may be to lower the incidence of Achilles tendinopathy by inhibiting L-type voltage-gated Ca2+ channel (including CaV1.2) signaling in tenocytes. Our finding will provide a rationale for further investigation of this association, including a potential for repurposing FDA-approved generic CCBs to prevent or treat Achilles tendinopathy.

Overcoming Confounding to Characterize the Effects of Calcium Channel Blockers.

Overcoming Confounding to Characterize the Effects of Calcium Channel Blockers.

Impact of Gene Polymorphism on Pharmacokinetics and Pharmaco-dynamics of Calcium Channel Blockers: A Narrative Review

A class of drugs known as calcium channel blockers (CCBs) is used to treat hypertension, angina, and arrhythmias. There are two subcategories of this medication class: dihydropyridines and non-dihydropyridines. Studies on CYP3A5*3, AGTR1 rs275653, ABCB1 (MDR1) rs1045642, and POR*28 A503V have all investigated the effects of SNPs on CCBs. This study will carry out more research to ascertain which SNPs have the most influence on the effectiveness of CCBs. The narrative reviews in this article come from a variety of sources. We performed searches in Pubmed, ScienceDirect, and Google Scholar using the terms "calcium channel blocker," "efficacy," "blood pressure response," "pharmacokinetic," and "polymorphism" OR "genetic" OR "genomic" to find pertinent articles. When prescription antihypertensive medications, particularly calcium channel blockers, it is important to take into account certain gene variants for example CYP3A5*3/*3, CYP3A4 *1G/*1G, MDR1 C3435T , RyR3 gene rs877087 because of their considerable effects.

Exploring calcium channel blocker as a candidate drug for Pseudomonas aeruginosa through network pharmacology and experimental validation.

Calcium channel blocker (CCB) is known to possess antibacterial effects. We aimed to apply network pharmacology (docking and protein-protein interaction [PPI] analyses) to predict the potential targets and mechanisms of CCB against Pseudomonas aeruginosa (PA) as well as to verify the effect of these drugs. The chemical structures of three CCBs were obtained through the Drug Bank platform. The potential channel proteins, efflux pump proteins and ion channel proteins of CCB against bacteria were derived from the literature. These proteins were collected through the PDB and Uniprot platform. The binding mode of the docking complexes was simulated by the CB-Dock platform and Discovery Studio 2019 Client software. The PPI network was constructed by the String platform and Cytoscape 3.8.2 platform. GO was explained by the PANTHER platform. The pathway diagram was drawn with the Pathway Builder Tool 2.0 software. The inhibitory effect of CCB on PA was verified through antibacterial experiments. Finally, 76 proteins were obtained: the iron channel protein of PA demonstrated a good docking relationship with all three CCBs, and the optimum binding energy was approximately -9.0 kcal/mol. GO analysis (biological process [BP], cellular component [CC], and molecular function [MF]) of protein genes showed a good docking relationship (optimum binding energy <-8.0 kcal/mol). The MF annotation results indicated that the target of CCB may be present on the PA membrane protein. The ion channel protein PPI enrichment p-value was 6.65e-08, and PfeA showed the strongest correlation. The experimental results suggested that CCB could inhibit the growth of PA. CCB might be an effective and interesting antimicrobial treatment strategy as CCB can potentially inhibit the growth of PA.

Repurposing Antihypertensive and Statin Medications for Spinal Pain: A Mendelian Randomization Study.

Mendelian randomization (MR) study. To examine whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal pain (back or neck pain). Observational studies and a recent MR study have found associations between elevated blood pressure and a greater risk of back pain. Observational studies have found associations between hyperlipidemia and statin use and greater risk of back pain. No prior MR studies have examined the effects of antihypertensives or statins on spinal pain. This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies (GWAS). Sample sizes in exposure GWASs were n=757,601 (systolic blood pressure) and n=173,082 (low-density lipoprotein cholesterol), and n=1,028,947 for the outcome GWAS of spinal pain defined as health care seeking for any spinal pain-related diagnosis. Genes and cis-acting variants were identified as proxies for the drug targets of interest. MR analyses used inverse-variance weighted meta-analysis. The threshold for statistical significance after correction for multiple testing was P <0.0125. No statistically significant associations of these medications with spinal pain were found. However, findings were suggestive of a protective effect of beta-blockers on spinal pain risk (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72-0.98; P =0.03), and calcium channel blockers on greater spinal pain risk (OR 1.12, 95% CI 1.02-1.24; P =0.02). A protective effect of beta-blockers on spinal pain was suggested in the current study, consistent with findings from observational studies of various other pain phenotypes. The detrimental effect of calcium channel blockers on spinal pain suggested in the current study must be interpreted in the context of conflicting directions of effect on nonspinal pain phenotypes in other observational studies.This Mendelian randomization study examined whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal.This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies ranging size from 173,082 to 1,028,947 adults.While no statistically significant associations were found, a protective effect of beta-blockers on spinal pain was suggested (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72 to 0.98; p= 0.03), as was a detrimental effect of calcium channel blockers on spinal pain (OR 1.12, 95% CI 1.02 to 1.24; p= 0.02).

Effect of Calcium Channel Blocker on Labor Curve in Pregnant Individuals with Chronic Hypertension.

This study aimed to compare the labor progress between individuals who received calcium channel blocker (CCB) and those who did not receive CCB during labor. This was a secondary analysis of a retrospective cohort study of individuals with chronic hypertension who underwent vaginal delivery at a tertiary care center from January 2010 to December 2020. We excluded individuals with prior uterine surgeries and a 5-minute Apgar score of less than 5. We used a repeated-measures regression with a third-order polynomial function to compare the average labor curves according to antihypertensive medication. Estimates of the median (5th-95th percentile) traverse times between two dilations were computed using interval-censored regression. Of 285 individuals with chronic hypertension, 88 (30.9%) received CCB. Individuals who received CCB during labor compared with those who did not were more likely to deliver at earlier gestational age and to have pregestational diabetes and superimposed preeclampsia (p < 0.01). The progress of labor in the latent phase was not found to be significantly different between both groups (median: 11.51 vs. 8.74 hours; p = 0.08). However, after stratification by parity, nulliparous individuals who received CCB during labor were more likely to have a longer latent phase of labor (median: 14.4 vs. 8.5 hours; p = 0.03) CONCLUSION: A calcium channel blocker may slow the latent phase of labor in individuals with chronic hypertension. Aiming to minimize intrapartum iatrogenic interventions, allowing adequate time for pregnant individuals during the latent phase of labor is especially important if individuals are on a calcium channel blocker. · Calcium channel blockers seem to be associated with a longer latent phase of labor.. · The effect of calcium channel blocker on labor was not observed in multiparous individuals.. · Allowing adequate labor time for individuals taking calcium channel blocker is important..

Blood pressure, calcium channel blockers, and the risk of prostate cancer: a Mendelian randomization study.

Observational studies have found some evidence of an association between elevated blood pressure and prostate cancer risk; however, the results are inconclusive. We tested whether systolic blood pressure (SBP) influences prostate cancer risk and evaluated the effect of calcium channel blockers (CCB) on the disease using Mendelian randomization (MR) approach. We used 278 genetic variants associated with SBP and 16 genetic variants in CCB genes as instrumental variables. Effect estimates were obtained from the UK Biobank sample of 142,995 males and from PRACTICAL consortium (79,148 cases and 61,106 controls). For each 10mm Hg increase in SBP the estimated effect was OR 0.96 (0.90-1.01) for overall prostate cancer; and OR 0.92 (0.85-0.99) for aggressive prostate cancer. The MR-estimated effect of a 10mm Hg- SBP lowering through CCB genetic variants was OR 1.22 (1.06-1.42) for all prostate cancers and OR 1.49 (1.18-1.89) for aggressive prostate cancer. The results of our study did not support a causal relationship between SBP and prostate cancer; however, we found weak evidence of a protective effect of high SBP on aggressive prostate cancer and we found that blocking calcium channel receptors may increase prostate cancer risk.

Clinical Outcomes of Calcium-Channel Blocker vs Beta-Blocker: From the Korean Acute Myocardial Infarction Registry

BackgroundAlthough current guidelines recommend beta-blockers (BBs) after acute myocardial infarction (AMI), the role of calcium-channel blockers (CCBs) has not been well investigated, especially nondihydropyridine. ObjectivesThis study aimed to compare the effects of CCBs on cardiovascular outcomes compared with BBs in AMI because patients from East Asia have a higher incidence of a vasospastic angina component compared with Western countries. MethodsAmong 15,628 patients enrolled in the KAMIR-V (Korean Acute Myocardial Infarction Registry-V), we evaluated 10,650 in-hospital survivors who were treated with either CCBs or BBs. We applied a propensity score for 1:4 pair matching of baseline covariates and Cox regression to compare CCBs and BBs. The primary endpoint was all-cause death at 1 year. The secondary endpoints were 1-year major adverse cardiac and cerebrovascular events, which was the composite of cardiac death, myocardial infarction, revascularization, and readmission due to heart failure and stroke. ResultsThere was a significant interaction with the treatment arm with left ventricular ejection fraction (LVEF) (P for interaction = 0.011). CCB groups at discharge had higher 1-year cardiac death and major adverse cardiac and cerebrovascular events for patients with LVEF <50% (HR: 4.950; 95% CI: 1.329-18.435; P = 0.017; and HR: 1.810; 95% CI: 1.038-3.158; P = 0.037, respectively) but not for patients with LVEF ≥50% (HR: 0.699; 95% CI: 0.435-1.124; P = 0.140). ConclusionsCCB therapy did not increase adverse cardiovascular events for patients after AMI with preserved LVEF. CCBs can be considered as an alternative for BBs in East Asian patients after AMI with preserved LVEF.

Nicardipine‐induced acute respiratory failure: Case report and literature review

Hypoxic pulmonary vasoconstriction (HPV) is a major physiological mechanism that prevents the development of hypoxemia secondary to a regional decrease in the ventilation-perfusion ratio (the intrapulmonary shunt effect). Calcium plays a critical role in the cellular response to hypoxia and the regulation of the pulmonary vascular tone. Therefore, calcium channel antagonists such as nicardipine have the potential to interfere with the pulmonary response to hypoxia, increasing intrapulmonary blood shunt and thus worsening underlying hypoxemia. This article reports the case of a 40-year-old man suffering from lobar pneumonia, who developed a rapidly progressing hypoxemia after starting nicardipine infusion for blood pressure control. After ruling out all major causes of hypoxemic respiratory failure, the involvement of the calcium channel antagonist was strongly suspected. Hypoxemia caused by HPV release is an underreported side effect of calcium channel blockers. There are few clinical reports that describe the occurrence of this adverse event, and to our knowledge, only one other publication describes a patient suffering from infectious pneumopathy. In this article, we discuss the cellular mechanisms behind the HPV, as well as the pharmacology of calcium channel antagonists and their involvement in the development of acute respiratory failure. The purpose of this report is to remind clinicians dealing with patients affected by acute hypoxemia that pharmacologic HPV inhibition should be considered as part of the differential diagnosis, thus avoiding unnecessary costly and time-consuming assessments.

The inhibitory effect of escitalopram on mouse detrusor contractility: The role of L-type calcium channels

Selective serotonin reuptake inhibitors (SSRIs) are associated with urinary problems attributed to their central effects. ESC is a preferred SSRI and several case reports described that ESC is related to urinary retention. However, the direct effect of ESC on detrusor contractility is still not completely elucidated. Thus, we investigated the effect of ESC on detrusor contractility and mechanism(s) of its action in isolated mouse detrusor strips. Molecular docking and measurement of intracellular calcium were performed to determine the possible calcium channel blocking effect of ESC. The contractile responses to carbachol (CCh), KCl and electrical field stimulation of detrusor strips were significantly abolished by ESC (10 or 100 μM). ESC relaxed KCl-precontracted detrusor strips concentration-dependently, which was not affected by tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. ESC (10 or 100 μM) reduced both the CaCl2- and CCh-induced contractions under calcium-free conditions, indicating the role of calcium-involved mechanisms in ESC-mediated relaxation. Furthermore, ESC significantly decreased Bay K8644-induced contraction and the cytosolic calcium level in fura-2-loaded A7r5 cells. Molecular docking study also revealed the potential of ESC to bind L-type calcium (Cav1) channels. Our results demonstrate that ESC inhibits detrusor contractility via blocking Cav1 channels, which provides evidence for the direct effect of ESC on detrusor contractility and its mechanism.