Effects Of Calcium Channel Blockers Research Articles

The Cardiac Protective Effects of Calcium Channel Blockers and Nitroglycerin in Cardiac Surgery: A Meta-analysis of Random Controlled Trials

The Cardiac Protective Effects of Calcium Channel Blockers and Nitroglycerin in Cardiac Surgery: A Meta-analysis of Random Controlled Trials

Effect of calcium channel blockers on influenza incidence: a population-based retrospective cohort study using administrative claims data in Japan

ObjectivesLaboratory experiments have indicated that calcium channel blockers (CCBs) inhibit the entry and replication of influenza A virus in cells. However, no clinical studies have assessed the incidence of influenza...

Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer

PurposePancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes.MethodsA retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan–Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival.Results4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4–7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8–7.8) vs. 6.7 months (95% CI 6.4–7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7–11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5–8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9–22%) and 14.8% (95% CI 11.1–19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2–4.4%).ConclusionOur results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.

Effects of calcium channel blockers in patients with heart failure with preserved ejection fraction: A protocol for systematic review and meta-analysis.

Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance. Due to the frequent coexistence of hypertension in HFpEF patients, the use of anti-hypertensive medications is common in their treatment. While many cohort studies and several randomized controlled trials (RCTs) have examined the effectiveness of various anti-hypertensive drugs such as beta-blockers and renin-angiotensin system inhibitors in HFpEF, the role of calcium channel blockers (CCBs) remains uncertain. Despite several RCTs and cohort studies exploring the effects of CCBs on prognosis and exercise capacity in HFpEF patients, the findings have been inconsistent, likely due to limited statistical power and/or variations in study design. Therefore, our aim is to conduct a systematic review and meta-analysis of studies on the effects of CCBs in these patients. This meta-analysis will include RCTs and cohort studies on the effect of CCBs in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome of interest will be prognosis. The secondary outcome of interest will be exercise capacity. Synthesizing our meta-analytical results with expert consensus could contribute to the formulation of updated clinical guidelines. Our systematic review and meta-analysis will provide directions for future research on the use of CCBs in HFpEF patients. INPLASY202430097.

Non-small cell lung cancer sensitisation to platinum chemotherapy via new thiazole-triazole hybrids acting as dual T-type CCB/MMP-9 inhibitors

Cisplatin remains the unchallenged standard therapy for NSCLC. However, it is not completely curative due to drug resistance and oxidative stress-induced toxicity. Drug resistance is linked to overexpression of matrix metalloproteinases (MMPs) and aberrant calcium signalling. We report synthesis of novel thiazole-triazole hybrids as MMP-9 inhibitors with T-type calcium channel blocking and antioxidant effects to sensitise NSCLC to cisplatin and ameliorate its toxicity. MTT and whole cell patch clamp assays revealed that 6d has a balanced profile of cytotoxicity (IC50 = 21 ± 1 nM, SI = 12.14) and T-type calcium channel blocking activity (⁓60% at 10 μM). It exhibited moderate ROS scavenging activity and nanomolar MMP-9 inhibition (IC50 = 90 ± 7 nM) surpassing NNGH with MMP-9 over −2 and MMP-10 over −13 selectivity. Docking and MDs simulated its receptor binding mode. Combination studies confirmed that 6d synergized with cisplatin (CI = 0.69 ± 0.05) lowering its IC50 by 6.89 folds. Overall, the study introduces potential lead adjuvants for NSCLC platinum-based therapy.

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 0.78-3.28 per 5 mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47-5.33, and vasodilators: 2.92, 95% CI 1.08-4.77). 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. Eighty-six proteins were related to lifespan, of which four proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan. Beta-blockers, 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.

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.

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.

Interaction between tacrolimus and calcium channel blockers based on CYP3A5 genotype in Chinese renal transplant recipients.

To investigate the effect of calcium channel blockers (CCBs) on tacrolimus blood concentrations in renal transplant recipients with different CYP3A5 genotypes. This retrospective cohort study included renal transplant recipients receiving tacrolimus-based immunosuppressive therapy with or without CCBs in combination. Patients were divided into combination and control groups based on whether or not they were combined with CCBs, and then further analyzed according to the type of CCBs (nifedipine/amlodipine/felodipine). Propensity score matching was conducted for the combination and the control groups using SPSS 22.0 software to reduce the impact of confounding factors. The effect of different CCBs on tacrolimus blood concentrations was evaluated, and subgroup analysis was performed according to the patients' CYP3A5 genotypes to explore the role of CYP3A5 genotypes in drug-drug interactions between tacrolimus and CCBs. A total of 164 patients combined with CCBs were included in the combination groups. After propensity score matching, 83 patients with nifedipine were matched 1:1 with the control group, 63 patients with felodipine were matched 1:2 with 126 controls, and 18 patients with amlodipine were matched 1:3 with 54 controls. Compared with the controls, the three CCBs increased the dose-adjusted trough concentration (C0/D) levels of tacrolimus by 41.61%-45.57% (P < 0.001). For both CYP3A5 expressers (CYP3A5*1*1 or CYP3A5*1*3) and non-expressers (CYP3A5*3*3), there were significant differences in tacrolimus C0/D between patients using felodipine/nifedipine and those without CCBs (P < 0.001). However, among CYP3A5 non-expressers, C0/D values of tacrolimus were significantly higher in patients combined with amlodipine compared to the controls (P = 0.001), while for CYP3A5 expressers, the difference in tacrolimus C0/D values between patients with amlodipine and without was not statistically significant (P = 0.065). CCBs (felodipine/nifedipine/amlodipine) can affect tacrolimus blood concentration levels by inhibiting its metabolism. The CYP3A5 genotype may play a role in the drug interaction between tacrolimus and amlodipine. Therefore, genetic testing for tacrolimus and therapeutic drug monitoring are needed when renal transplant recipients are concurrently using CCBs.

Anti-hypertensives associated with survival in cancer patients receiving immunotherapy: new evidence from a real-world cohort study and meta-analysis.

The efficacy of immune checkpoint inhibitors (ICIs) in cancer patients taking anti-hypertensive drugs is still not well established. To elucidate the effect of anti-hypertensive drugs on the clinical outcome of cancer patients receiving immunotherapy. A retrospective cohort study and meta-analysis. We conducted a real-world retrospective study of cancer patients treated with immunotherapy at two tertiary centers between January 2019 and June 2023, with primary outcomes being overall survival (OS) and progression-free survival (PFS). In addition, we performed a meta-analysis to synthesize currently relevant clinical studies. A retrospective clinical study of 336 patients from 2 centers suggested that the use of anti-hypertensive drugs was related to a preferable OS (hazard ratio (HR) = 0.55, 95% confidence interval (CI): 0.33-0.90) compared to non-users. For PFS, no significant correlation was detected (HR = 0.71, 95% CI: 0.49-1.03). Further analysis revealed that renin-angiotensin system inhibitor (RASi) and calcium channel blocker (CCB) have a synergistic effect with ICIs. In addition, subgroup analysis found that the benefits of RASi or CCB in combination with ICIs are greater in women or patients ⩾65 years of age. There was better disease control in lung cancer patients using RASi, and a significantly longer OS was observed in patients with gastrointestinal tumors taking CCB. Meta-analysis suggested that anti-hypertensive drugs were associated with improved OS, but only the combination of RASi and immunotherapy showed a synergistic effect. No significant correlation with OS was found for other anti-hypertensive drugs, and there was no overall positive effect on PFS. Our study found that use of anti-hypertensive drugs, particularly RASi or CCB, was associated with improved OS in patients undergoing immunotherapy. The synergistic effects of RASi or CCB with ICIs were more pronounced in females or elderly. RASi or CCB exhibited different benefits in various types of tumors. These findings provide valuable insights for treating cancer patients with hypertension.

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.