Sex differences and disparities in cardiovascular outcomes of COVID-19

Bugiardini, Raffaele; Nava, Stefano; Caramori, Gaetano; Yoon, Jinsung; Badimon, Lina; Bergami, Maria; Cenko, Edina; David, Antonio; Demiri, Ilir; Dorobanţu, Maria; Fronea, Oana Florentina Gheorghe; Janković, Radmilo; Kedev, Sasko; Ladjević, Nebojša; Lasica, Ratko; Loncar, Goran; Mancuso, Giuseppe; Mendieta, Guiomar; Miličić, Davor; Mjehović, Petra; Pašalić, Marijan; Petrović, Milovan; Poposka, Lidija; Scarpone, Marialuisa; Stefanovic, Milena; Schaar, Mihaela van der; Vasiljević, Zorana; Vavlukis, Marija; Vega, María Laura; Vukomanovic, Vladan; Zdravković, Marija; Manfrini, Olivia

doi:10.1093/cvr/cvad011

Cited by 4 publications

(1 citation statement)

References 24 publications

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“…The main experiments in this study were performed on cardiac muscle cells from 3‐month‐old male Wistar rats. In further studies, we will investigate the influence of age and gender on the described pathomechanisms, and on the evolution and severity of dysfunction (Bugiardini et al, 2023; Ferdinandy et al, 2019; Ferdinandy et al, 2023). In addition, it would be important to determine the influence of mRNA‐1273 and BNT162b2 on the function of muscle cells specific to the cardiac conduction system, which are histologically differentiated from working myocardial cells.…”

Section: Discussionmentioning

confidence: 99%

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Schreckenberg,

Woitasky,

Itani

et al. 2023

British J Pharmacology

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Background and PurposeTo protect against SARS‐CoV‐2 infection, the first mRNA‐based vaccines, Spikevax (mRNA‐1273, Moderna) and Comirnaty (BNT162b2, Pfizer/Biontech), were approved in 2020. The structure and assembly of the immunogen – in both cases, the SARS‐CoV‐2 spike (S) glycoprotein – are determined by a messenger RNA sequence that is translated by endogenous ribosomes. Cardiac side effects, which for the most part can be classified by their clinical symptoms as myo‐ and/or pericarditis, can be caused by both mRNA‐1273 and BNT162b2.Experimental ApproachAs persuasive theories for the underlying pathomechanisms have yet to be developed, this study investigated the effect of mRNA‐1273 and BNT162b2 on the function, structure, and viability of isolated adult rat cardiomyocytes over a 72 h period.Key ResultsIn the first 24 h after application, both mRNA‐1273 and BNT162b2 caused neither functional disturbances nor morphological abnormalities. After 48 h, expression of the encoded spike protein was detected in ventricular cardiomyocytes for both mRNAs. At this point in time, mRNA‐1273 induced arrhythmic as well as completely irregular contractions associated with irregular as well as localized calcium transients, which provide indications of significant dysfunction of the cardiac ryanodine receptor (RyR2). In contrast, BNT162b2 increased cardiomyocyte contraction via significantly increased protein kinase A (PKA) activity at the cellular level.Conclusions and ImplicationsHere we demonstrated for the first time, that in isolated cardiomyocytes, both mRNA‐1273 and BNT162b2 induce specific dysfunctions that correlate pathophysiologically to cardiomyopathy. Both RyR2 impairment and sustained PKA activation may significantly increase the risk of acute cardiac events.

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Section: Discussionmentioning

confidence: 99%

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Schreckenberg,

Woitasky,

Itani

et al. 2023

British J Pharmacology

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Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID‐19 and Preexisting Cardiovascular Disease

Bergami

Manfrini

Nava

et al. 2023

JAHA

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Background Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID‐19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results This study was conducted using data from the ISACS‐COVID‐19 (International Survey of Acute Coronavirus Syndromes‐COVID‐19) registry. Patients with a confirmed diagnosis of SARS‐CoV‐2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30‐day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06–2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69–1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42–0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75–2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other ( P interaction =0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34–3.90]). Conclusions These findings suggest that azithromycin use in patients with COVID‐19 and prior history of CVD is significantly associated with an increased risk of AHF and all‐cause 30‐day mortality. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05188612.

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Cardiometabolic sex differences in adults born small for gestational age

Rodríguez-López,

Sepúlveda-Martínez,

Bernardino

et al. 2023

Front. Cardiovasc. Med.

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AimThis study aimed to assess the cardiometabolic sex similarities and differences in adults born small for gestational age.MethodsThis study was an ambispective cohort study from a birth registry in Barcelona, Spain, including 523 adult participants (20–40 years-old) subdivided as born small for gestational age (SGA, if birth weight <10th centile) or adequate fetal growth for gestational age (AGA). Cardiometabolic health was assessed by echocardiography, electrocardiogram, blood pressure measurement, vascular ultrasound, anthropometric measurements, and serum glycemia and lipid profile. Stratified analyses by sex were performed by estimation of adjusted absolute difference (AAD) using inverse probability weighting.ResultsCompared with AGA, the stratified analyses by sex showed a more pronounced reduction in ejection fraction [AAD: female −1.73 (95% CI −3.2 to −0.28) vs. male −1.33 (−3.19 to 0.52)] and increment in heart rate [female 3.04 (0.29–5.8) vs. male 2.25 (−0.82 to 5.31)] in SGA females compared with SGA males. In contrast, a more pronounced reduction in PR interval [female −1.36 (−6.15 to 3.42) vs. male −6.61 (−11.67 to −1.54)] and an increase in systolic blood pressure [female 0.06 (−2.7 to 2.81) vs. male 2.71 (−0.48 to 5.9)] and central-to-peripheral fat ratio [female 0.05 (−0.03 to 0.12) vs. male 0.40 (0.17–0.62)] were mainly observed in SGA male compared with SGA female.ConclusionsSex differences were observed in the effect of SGA on cardiometabolic endpoints with female being more prone to cardiac dysfunction and male to electrocardiographic, vascular, and metabolic changes. Future research including sex-stratification data is warranted.

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Sex differences and disparities in cardiovascular outcomes of COVID-19

Cited by 4 publications

References 24 publications

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Cardiac side effects of RNA‐based SARS‐CoV‐2 vaccines: Hidden cardiotoxic effects of mRNA‐1273 and BNT162b2 on ventricular myocyte function and structure

Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID‐19 and Preexisting Cardiovascular Disease

Cardiometabolic sex differences in adults born small for gestational age

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