{"doi":"10.1093/function/zqad054","title":"Overcoming Confounding to Characterize the Effects of Calcium Channel Blockers","abstract":"A Perspective on \"A Reappraisal of the Effects of L-type Ca 2 + Channel Blockers on Store-oper a ted Ca 2 + Entry and Heart Failure\" Hypertension is the leading cause of death globally, accounting for 10.4 million deaths ann uall y, with long-term effects that include an increased risk of m y ocardial infar ction, heart failur e, str oke, r etinopath y, and kidne y disease. 1 Current therapies for hypertension include calcium c hannel bloc kers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin r ece ptor b lockers (ARBs), thiazide diur etics, and beta b lockers. 1 Of these, CCBs are now one of the most popular and are currently first-line agents, with numerically greater reductions in blood pr essur e in certain patient groups. 2 One of the most popular is the dih ydrop yridine CCB amlodipine, which can be taken daily, is effecti v e, and has r elati v el y few side effects.Recentl y, J ohnson et al. 3 have raised questions regarding the safety of amlodipine and CCBs in general, as they r e ported that all CCBs activ ated stor e-operated Ca 2 + entr y (SOCE) in addition to their wellesta b lished r ole in the inhibition of v olta ge-oper ated Ca 2 + c hannels.Mor eov er, they observ ed that CCBs stim ulated SOCE in rat aortic smooth muscle cells and promoted greater proliferation, whic h w ould be expected to hav e negati v e impacts on v ascular function.These findings are consistent with previous studies wher e b lockade or genetic deletion of SOCE w as shown to impair vascular smooth muscle cell proliferation, potentially impacting sev eral v ascular diseases. 4In fact, genetic v ariation in the STIM1 gene was identified as a modifier gene for the spontaneously hypertensi v e rat. 5 Understanding the actions of CCB on SOCE ther efor e has implications on many vascular diseases.Consistent with this idea, Johnson et al. also performed an epidemiological analysis of 20 000 patient records that suggested that CCBs increased the risk of heart failure.This finding was surprising as it was counter to the many clinical trials that underpin current clinical guidelines and runs counter to the clinical experience of many hypertension and heart failure specialists.","journal":"Function","year":2023,"id":387649,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9663,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":443825,"name":"Paul B. Rosenberg","orcid":"0000-0002-5659-160X","position":1,"is_corresponding":false},{"id":354436,"name":"Sudarshan Rajagopal","orcid":"0000-0002-3443-5040","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T01:18:08.845494Z","pmid":"37841524","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}