Role 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.

Is There a Role for Calcium Channel Blockers in the Contemporary Treatment Paradigm for Pulmonary Arterial Hypertension?

Is There a Role for Calcium Channel Blockers in the Contemporary Treatment Paradigm for Pulmonary Arterial Hypertension?

Role of antihypertensive medicines in prostate cancer: a systematic review

BackgroundHypertension is associated with the risk of prostate cancer (PCa) and its progression, however, it remains unclear whether antihypertensive medicines alter PCa risk or prognosis. This systematic review evaluated the role of calcium channel blockers (CCBs) and renin-angiotensin system (RAS) inhibitors in the risk and prognosis of PCa. This review was performed in line with PRISMA 2020 guidelines.MethodsEligible studies comprised peer-reviewed observational studies which reported the role of CCBs and RAS inhibitors in PCa, had accessible full texts, and were written in English. Using a combination of keywords, 5 electronic bibliographic databases which included Web of Science, EMBASE, PubMed, Google Scholar and Scopus were searched.ResultsA total of 1,346 studies were retrieved and 18 met the inclusion criteria. Thirteen studies reported reduced or no associated risk, improved prognosis, and survival with the use of RAS inhibitors. Studies on CCBs showed evidence of associated risk of PCa. Data extraction from retrieved studies focused on included study characteristics, setting, authors, year, outcomes of interest, and risk ratios. The quality assessment of included studies by the National Heart, Lung, and Blood Institute study assessment tools, showed that all studies had good quality.ConclusionsThe use of RAS inhibitors was mostly associated with lower risks or improved prognosis of PCa. CCBs may also be associated with risks of PCa. This suggests that high-risk patients managed with CCBs should be actively monitored for PCa. However, there is need for further evidence from large-scale prospective, controlled cohort studies to determine any influence of CCBs on PCa.

Benidipine impairs innate immunity converting sublethal to lethal infections in a murine model of spotted fever rickettsiosis.

Spotted fever group rickettsiae are tick-borne obligate intracellular bacteria that infect microvascular endothelial cells. Humans and mammalian infection results in endothelial cell barrier dysfunction and increased vascular permeability. We previously demonstrated that treatment of Rickettsia parkeri-infected cells with the calcium channel blocker benidipine significantly delayed vascular barrier permeability. Thus, we hypothesized that benidipine, known to be safe and effective for other clinical processes, could reduce rickettsia-induced vascular permeability in vivo in an animal model of spotted fever rickettsiosis. Based on liver, lung and brain vascular FITC-dextran extravasation studies, benidipine did not reliably impact vascular permeability. However, it precipitated a deleterious effect on responses to control sublethal R. parkeri infection. Animals treated with benidipine alone had no clinical signs or changes in histopathology and splenic immune cell distributions. Benidipine-treated infected animals had marked increases in tissue and blood bacterial loads, more extensive inflammatory histopathologic injury, and changes in splenic architecture and immune cell distributions potentially reflecting diminished Ca2+ signaling, reduced innate immune cell activation, and loss of rickettsial propagation control. Impaired T cell activation by R. parkeri antigen in the presence of benidipine was confirmed in vitro with the use of NKT cell hybridomas. The unexpected findings stand in stark contrast to recent discussions of the benefits of calcium channel blockers for viral infections and chronic infectious or inflammatory diseases. A role for calcium channel blockers in exacerbation of human rickettsiosis and acute inflammatory infections should be evaluated by a retrospective review of patient's outcomes and medications.

Omega-conotoxin MVIIA reduces neuropathic pain after spinal cord injury by inhibiting N-type voltage-dependent calcium channels on spinal dorsal horn.

Spinal cord injury (SCI) leads to the development of neuropathic pain. Although a multitude of pathological processes contribute to SCI-induced pain, excessive intracellular calcium accumulation and voltage-gated calcium-channel upregulation play critical roles in SCI-induced pain. However, the role of calcium-channel blockers in SCI-induced pain is unknown. Omega-conotoxin MVIIA (MVIIA) is a calcium-channel blocker that selectively inhibits N-type voltage-dependent calcium channels and demonstrates neuroprotective effects. Therefore, we investigated spinal analgesic actions and cellular mechanisms underlying the analgesic effects of MVIIA in SCI. We used SCI-induced pain model rats and conducted behavioral tests, immunohistochemical analyses, and electrophysiological experiments (in vitro whole-cell patch-clamp recording and in vivo extracellular recording). A behavior study suggested intrathecal MVIIA administration in the acute phase after SCI induced analgesia for mechanical allodynia. Immunohistochemical experiments and in vivo extracellular recordings suggested that MVIIA induces analgesia in SCI-induced pain by directly inhibiting neuronal activity in the superficial spinal dorsal horn. In vitro whole-cell patch-clamp recording showed that MVIIA inhibits presynaptic N-type voltage-dependent calcium channels expressed on primary afferent Aδ-and C-fiber terminals and suppresses the presynaptic glutamate release from substantia gelatinosa in the spinal dorsal horn. In conclusion, MVIIA administration in the acute phase after SCI may induce analgesia in SCI-induced pain by inhibiting N-type voltage-dependent calcium channels on Aδ-and C-fiber terminals in the spinal dorsal horn, resulting in decreased neuronal excitability enhanced by SCI-induced pain.

Insights into the Pivotal Role of Calcium Channel Blockers and Its Nanoformulations in the Management of Hypertension

Insights into the Pivotal Role of Calcium Channel Blockers and Its Nanoformulations in the Management of Hypertension

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.

Role of calcium channel blocker in excessive mast cell degranulation

Here, I present a case of a female patient, age 45 years, for whom the uncontrolled mast cell degranulation created many issues related to allergy like, skin rash, itching, breathing discomfort, frequent throat infection, GERD, migraine, fibromyalgia, peripheral neuropathy, depression, anxiety disorder, constipation etc. For the patient, it was observed that calcium channel blockers seem to control the unnecessary and uncontrolled mast cell degranulation. CCB seemed to have a role to play in mast cell degranulation.

Efonidipine Exerts Cerebroprotective Effect by Down-regulation of TGF-β/SMAD-2-Dependent Signaling Pathway in Diabetic Rats.

Calcium overload and hyperglycemia are risks of stroke onset in diabetics. Our study was designed to elucidate the beneficial role of calcium channel blockers by targeting voltage-gated calcium channels in diabetes-associated cerebrovascular complications. Diabetes was induced using the neonatal streptozotocin rat model. After confirmation of diabetes, middle cerebral artery occlusion (MCAO) was carried out. The pre-treatment with 1 mg/kg/day efonidipine was administered for the period of 4 weeks. After 24 h of ischemic induction surgery, the neurological score was determined, and blood was collected for determination of biochemical parameters. Treatment with efonidipine showed a significant reduction in post-ischemic brain infract volume, brain hemisphere weight difference, neurological score, Na+-K+ ATPase activity, serum CK-MB, and LDH levels in normoglycemic and hyperglycemic MCAO-induced animals. While no significant changes in glucose and lipid levels were observed by treatment, efonidipine significantly decreased the levels of malondialdehyde, acetylcholine esterase, and nitrite levels and increased the levels of antioxidant markers in both normoglycemic and hyperglycemic MCAO animals. TGF-β and VEGF were found to be down-regulated after treatment with efonidipine in gene expression study. In conclusion, the study data supports the cerebroprotective role of efonidipine in diabetic animals possibly through TGF-β/SMAD-2 signaling pathway.

Clinical study of role of calcium channel blocker (efonidipine) in uncomplicated mild to moderate primary hypertension

Clinical study of role of calcium channel blocker (efonidipine) in uncomplicated mild to moderate primary hypertension

Current perspective on the use of calcium channel blockers to treat hypertensive patients: the role of lercanidipine.

The symposium 'Current perspective on the use of calcium channel blockers in the treatment of hypertensive patients', held in Stresa (Italy) on 28th and 29th June 2018 with the participation of the main experts in the field of hypertension from all over the world, reviewed the role of calcium channel blockers in the management of hypertension. Considering the new European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines presented at the last European Society of Hypertension meeting in Barcelona in June 2018, a special attention was focused on lercanidipine. In this article, the main highlights of the symposium were summarized.

Amlodipine-induced gingival overgrowth in the peri-implant region: a review and case report

Gingival overgrowth is a known side-effect of the antihypertensive drug amlodipine, but the risk of mucosal overgrowth around dental implants has been less well documented. This article discusses the role of calcium channel blockers in drug-induced mucosal overgrowth around dental implants and describes the preventive and surgical management of the case. CPD/Clinical Relevance: The report describes the management of a patient with an implant-supported restoration who presented with peri-implantitis and drug-induced mucosal overgrowth. The review discusses how amlodipine and other medications, commonly associated with drug-induced gingival overgrowth, impact on the management of implant patients.

The role of calcium channel blockers in the treatment of diabetic nephropathy

Diabetic nephropathy (DNP) is a chronic renal disease (CRD) and a major cause of illness and premature death in peoplewith diabetes mellitus (DM). It is the single most important cause of end-stage renal disease in the Western world andaccounts for more than a quarter of all end-stage renal diseases. This article reviews the current development in DNP and thetherapeutic challenge with particular reference to the role of calcium channel blockers. Moreover, renal ischaemia hastens theprogression of DNP. Diltiazem and amlodipine have a tendency to reverse the changed parameters toward normal values butdo not affect the biochemical parameters. Generally speaking, diltiazem is better than amlodipine in reversing biochemicaland histopathological changes produced by DNP, and captopril reverses most of the changed parameters with the exceptionof the histopathological changes. These agents have nephroprotective properties and delay the progression of DNP.

Blood pressure lowering effect of calcium channel blockers on perioperative hypertension: A systematic review and meta-analysis.

Background:Acute perioperative hypertension has been associated with poor outcomes of surgery, and the role of calcium channel blockers (CCB) on controlling perioperative blood pressure (BP) remains controversial. Thus, this meta-analysis was designed to assess the efficacy and safety of CCB in treating perioperative hypertension compared with other antihypertensive agents.Methods:PubMed, Medline, Cochrane, and EMABSE databases was systematically searched up to January 2018 for randomized control trials (RCTs) or other control studies comparing the efficacy of CCB versus other antihypertensive medicines for perioperative hypertension modulation. The efficacy and safety of CCB in treating perioperative hypertension were assessed through pooling mean difference (MD) with its 95% confidence interval (CI) or risk ratio (RR) with its 95% CI.Results:In total, 14 studies were included in the meta-analysis. There is no significant difference regarding successful treatment (RR = 2.64, 95% CI: 0.95, 7.29; I2 = 97%, P <.05), systolic blood pressure (SBP) (MD = −7.05, 95% CI: −16.27, 2.17; I2 = 78%, P <.05), overall adverse events (RR = 0.88, 95% CI: 0.66, 1.16; I2 = 54%, P = .02), atrial fibrillation (RR = 0.80, 95% CI: 0.60, 1.07; I2 = 32%, P = .20) and heart rates (MD = −1.05, 95% CI: −7.81, 5.71; I2 = 84%, P < .05) between patients treated by CCB and other drugs. In the subgroup analysis, statistical significance can be observed regarding successful treatment (RR = 3.46, 95%CI: 1.67, 7.18; I2 = 84%, P <.05) and postoperative SBP (MD = −9.98, 95%CI: −20.03, 0.08; I2 = 97%, P <.05) in the RCTs subgroup.Conclusion:CCB was highly effective and well tolerated for treating perioperative hypertension.

Role of Calcium Channel Blockers in Myocardial Preconditioning

Abstract Coronary heart disease is the leading cause of mortality and morbidity worldwide. The effects of coronary heart disease are usually attributable to the detrimental effects of acute myocardial ischaemia-reperfusion injury. Newer strategies such as ischaemic or pharmacological preconditioning have been shown to condition the myocardium to ischaemia-reperfusion injury and thus reduce the final infarct size. This review investigates the role of calcium channel blockers in myocardial preconditioning. Additionally, special attention is given to nicorandil whose mechanism of action may be associated with the cardioprotective effects of preconditioning. There are still many uncertainties in understanding the role of these agents in preconditioning, but future research in this direction will certainly help reduce coronary heart disease.

Calcium channel blockade and survival in recipients of successful renal transplant: an analysis of the FAVORIT trial results.

IntroductionSingle-center and observational studies have suggested that calcium channel blocking agents may decrease the expression of sepsis in individual populations. In the renal transplant population, a role for calcium channel blockers in allograft protection and in prevention of sepsis has been postulated. We hypothesized that any important survival benefit or risk related to chronic use of calcium channel blocking agents should be discernable through an analysis of a large database of stable recipients of renal allografts who had enrolled in a large international trial.MethodsA retrospective analysis of 4,110 renal transplant recipients who enrolled in the international Folic Acid for Vascular Outcome Reduction in Transplantation trial between 2002 and 2007 and were followed until 2010 was undertaken comparing cohorts (FAVORIT) of patients either taking (n=1,436) or not taking (n=2,674) calcium channel blocking medications. The endpoint was all-cause mortality (cardiovascular, noncardiovascular mortality, or unknown). Results were adjusted for country, age, race, sex, smoker, systolic blood pressure, diabetes mellitus, low-density lipoprotein, and chronic kidney disease status.ResultsThere were no statistically significant differences in incidence rates of cardiovascular, noncardiovascular, and all-cause mortality between patients taking or not taking calcium channel blocking medications.ConclusionAlthough physiologic reasoning and small series results suggest a benefit for calcium channel blocking agents for allograft protection and sepsis prevention in immunosuppressed patients, we find no clear survival benefit in a large international renal transplant trial.

Abstract 12688: Long Term Use of Calcium Channel Blockers and Risk of Breast Cancer Development

Introduction: Calcium channel blockers (CCBs) are a mainstay in treating hypertension (HTN). Recently, Li et-al published a population based case-control study (JAMA 2013; 289:2354) reporting CCB use to be associated with incident breast cancer (odds ratio 2.6). We prospectively analyzed 2 Intermountain Healthcare (IHC) databases (db) to confirm or refute this provocative report. Methods: Two separate analyses were conducted using general patients (GP) seen at IHC and patients undergoing coronary angiography (CV) at IHC facilities. Subjects were females aged 50-70 with no history of breast cancer. Those prescribed CCB were matched 1:1 to subjects not on CCB based on age, race, tobacco, alcohol, body mass index, HTN and follow up time. Multivariable Cox proportional hazards regression was used for the primary analysis of time to incident breast cancer by CCB use adjusting for history of other cancers and family history of breast cancer. Results: A total of 2612 GP subjects (cases/controls) and 1106 CV subjects (cases/controls) were studied. In the GP db, there was a statistically significant increased risk of breast cancer for subjects using CCB (HR=1.58; 95% CI: 1.10-2.26). Risk was also associated with a positive family history (HR=2.79; 1.96-3.97) and a personal history of cancer (HR=1.87; 1.07-3.26). Breast cancer predominantly developed in &lt;5 y of follow up (64% of cases). However, a reverse relationship was found in the CV db, where the HR was 0.51 (95% CI: 0.27-0.97). This observation was found despite consistent associations with several secondary outcomes, including for incident diabetes, coronary and renal disease. Conclusion: A modest association between CCB use and incident breast cancer was observed in the GP db, but results were not reproducible in the CV db. Given lack of a credible mechanism and failure of previous randomized CCB studies to detect a signal, we interpret these modest and conflicting associations to likely represent uncorrected confounding, e.g. prescriber bias or drug interactions. Similarly, we believe the results of Li et-al may represent confounding. Given the important role of CCBs in clinical medicine, further studies are warranted, including randomized trials to assess CCB safety with respect to breast cancer risk.

Clinical implications of the 2013 ESH/ESC hypertension guidelines: targets, choice of therapy, and blood pressure monitoring.

The European Society of Hypertension (ESH)/European Society of Cardiology (ESC) 2013 guidelines for the management of arterial hypertension included simplified blood pressure (BP) targets across patient groups, more balanced discussion on monotherapy vs. combination therapy, as well as reconfirmation of the importance of out-of-office BP measurements. In light of these updates, we wished to review some issues raised and take a fresh look at the role of calcium channel blocker (CCB) therapy; an established antihypertensive class that appears to be a favorable choice in many patients. Relaxed BP targets for high-risk hypertensive patients in the 2013 ESH/ESC guidelines were driven by a lack of commanding evidence for an aggressive approach. However, substantial evidence demonstrates cardiovascular benefits from more intensive BP lowering across patient groups. Individualized treatment of high-risk patients may be prudent until more solid evidence is available. Individual patient profiles and preferences and evidence for preferential therapy benefits should be considered when deciding upon the optimal antihypertensive regimen. CCBs appear to be a positive choice for monotherapy, and in combination with other agent classes, and may provide specific benefits beyond BP lowering. Ambulatory and home BP monitoring have an increasing role in defining the diagnosis and prognosis of hypertension (especially non-sustained); however, their value for comprehensive diagnosis and appropriate treatment selection should be more widely acknowledged. In conclusion, further evidence may be required on BP targets in high-risk patients, and optimal treatment selection based upon individual patient profiles and comprehensive diagnosis using out-of-office BP measurements may improve patient management.

Authors' reply (acute myocardial infarction and cocaine toxicity: One step closer).

Sir, The article of Senthilkumaran et al.[1] in response to our article[2] pertinently raises the rising concern of substance abuse induced coronary artery disease in Indian subcontinent. Some of the points raised by them however need further clarifications. First, the controversy of thrombolysis in our patient of cocaine induced myocardial infarction (CAMI). As per the current guidelines thrombolysis is not contraindicated in CAMI, though primary percutaneous intervention (PCI) is definitely the preferred option.[3] This strategy is even more relevant in a country like India, where majority of our health care facilities are non-PCI capable. We should not deprive these patients the benefit of timely thrombolysis when there are no other contraindications and primary PCI is not available. However, caution should be applied in thrombolytic therapy as cocaine users may have altered consciousness = induced fall and trauma, with some of the injuries not obvious on initial evaluation. Regarding our patient, we could not proceed with primary PCI due to financial constraints of the patient. Secondly, the role of calcium channel blockers in the treatment of patients with cocaine-associated acute coronary syndrome remains uncertain. Calcium channel blockers should not be used as a first-line treatment, but may be considered for patients who do not respond to benzodiazepines and nitroglycerin.[3] Regarding cardiac biomarkers, it was rightly pointed out that serum creatinine kinase level is not a reliable indicator of myocardial injury in cocaine users. This is the reason we went for additional measurement of troponine T in our patient. Finally, through this letter, we seize the opportunity to share the present status of the index patient who is on our close follow-up for almost 2.5 years now. Apart from the cardiac medications, he was made to attend a strict de-addiction program. Currently, he is asymptomatic and his left ventricular ejection fraction went up to more than 50%.

Challenges in hypotensive therapy: the role of calcium antagonists

The paper addresses the role of calcium channel blockers (CCB) in the treatment of patients with arterial hypertension and concomitant pathology. The authors present the findings of the recent studies on CCB effects on renal function, bronchial function, and systemic inflammation. This additional information on comorbidities is essential for the doctors’ choice of optimal individualised therapy.