Arterial stiffness and COVID‐19: A bidirectional cause‐effect relationship

• DOI: 10.1111/jch.14259
• Publication Date: 2021-05-06T08:28:25Z
• Authors: Sahrai Saeed; Giuseppe Mancia
• Keywords: Endothelial Dysfunction

Coronavirus disease 2019 (COVID-19) primarily affects the lungs but clinical manifestations vary markedly among patients involved. In more severe cases, COVID-19 can lead to acute respiratory distress syndrome (ARDS), multi-organ failure including cardiac injury and toxic shock with need for intensive care a ventilator support,1 while at opposite extreme signs symptoms be those of mild flu in many infection is asymptomatic. Since outbreak China, large number studies have consistently reported on cardiovascular (CV) complications which include injury, arrhythmias, diffuse endothelial damage leading microvascular thrombosis thromboembolic events. Evidence has also suggested that cardiac, vascular, renal, cerebral damages associated CV risk factors such as hypertension, diabetes, dyslipidemias, obesity increase progression its most lethal forms, presumably because pre-existing structural functional alterations organs affected by long-lasting blood pressure elevation metabolic weaken their resistance virus. Resistance virus may further reduced pathogenetic nature some these organ alterations, is, fact common cause factor-dependent complications, atherosclerosis, likely co-determined an inflammatory process adversely interact coronavirus.1 As far obesity, major component syndrome, concerned, relationship severity due association chronic low grade inflammation, higher leptin lower adiponectin levels, immune response dysregulation, abnormal pro-inflammatory cytokine production.2 The between increased arterial stiffness duration inflammation systemic diseases are well established.3 vascular structure function altered edema cells. Prior supported cross talk showing rheumatoid arthritis bowel than control subjects matched age, sex pressure.4 Hence, underlying states goes hand-in-hand stiffness. For all interactive factors, there basis vicious circle because, increasing traumatic effect intravascular pulsatile wall, stiffening favors atherosclerosis effect. same true COVID-19. multisystem hyperinflammation therefore detrimental effects vasculature both short long run. A practical example ethnic minorities who experience aggressive forms enhanced rates complications.5 Of note, substantial prevalence cluster target against coronavirus. During pandemic, research reserved little attention artery This justification been repeatedly shown paramount importance it: 1) predicts future hypertension people exhibit normal BP6, 7; 2) increases long-term events death, independently contribution other factors8; 3) flow transmission microvasculature. possibility part phenotype evidence known operate during affect distensibility, will discussed below. so only few small assessing impact (Table 1). initial field, Schnaubelt et al recently showed study 22 compared age- sex-matched controls, was reflected carotid-femoral or brachial-ankle pulse wave velocity (PWV).9 Median PWV 14.3 m/s acutely ill 11.0 (P =.007) non-COVID-19 patients. Similarly, median 19.9 16.0 =.019) controls. Both =.056) brachial ankle =.004) were non-survivors survivors. correlated length hospital stay. Furthermore, preliminary implications infection.10, 11 small, cross-sectional study, Ratchford young adults 3-4 weeks prior health assessment tested positive COVID-19, had significantly impaired flow-mediated dilation (FMD) artery, derived from PWV, healthy without infection.10 FMD expressed percentage change 2.71 ± 1.21% group 8.81 2.96% <.01) group. Carotid-femoral 5.83 0.62 5.17 0.66 controls Brachial-ankle (14.3 vs. m/s, P =.007). survivors (n = 11), stay (mean 12.6 4.3 days). COVID-19: 20 years Control: 23 Brachial Leg sPLM group: - (2.71 2.96%, <.01). (5.83 Retrospective All-cause mortality 50 days Finally, Rodilla ≥60 mmHg admission, surrogate marker stiffness, all-cause (adjusted odds ratio 1.27, =.0001) hospitalized patients.11 addition, individual case involving 55-year-old man no previously we several months after recovery patient sustained tachycardia elevated rest. We speculated activation renin-angiotensin sympathetic systems, inflammation-induced cytokine, volume overload hyperreninemia, vasculitis contributed exaggerated rest.12 However, whether this persistently heart rate consequence COVID-19-induced untreated persistent primary responsible factor incident matter well-designed prospective clarify. Endothelial dysfunction believed key element pathogenesis COVID-19-related damage.13-16 direct bilateral correlation accelerates each other.14, 17 COVID-19-dependent subintimal hemorrhage thrombosis, dysregulating tone, causing edema, matrix metalloproteinase levels remodeling.18 Indeed, principle one greater chance persist sequela materialize if post-infection fibrosis documented extends wall tissue, replaces elastic tissue component. potential mechanisms Figure 1. Another possible mechanism modification brought about cytokine-dependent cells given repeated demonstration close diseases.3, 4 Systemic storm result dysregulation gained much pandemic.1 dysfunction, oxidative stress, decreased nitric oxide secretion bioavailability, relaxation smooth muscle vasoconstriction modulus relaxed state. Increased viscosity hyperglycemia, hypoxia, disseminated coagulation (DIC), fibrinogen degradation products contributing (Figure 1).19 Upregulation cytokines tumor necrosis alpha (TNF-α) interleukins (ILs) (IL-6 IL-8), enhance platelet reactivity leukocytes form neutrophil extracellular traps (NETs) contributes pro-thrombotic state​ formation thrombi.20, 21 IL-6 causes permeability through oxide.15 Other theories SARS-CoV-2 infection-related mitochondrial inmitochondrial reactive oxygen species (ROS) production proposed.22 Mitochondrial ROS functions signaling molecule keeping basal hemostasis pathways balance. Enhanced dysfunctional mitochondria leads stress promotion subsequent lung It postulated induce premature aging telomere damage.22 important intermediate step morbid fatal events, damaged patterns irregular. These subendothelial plasma lipoprotein (LDL) deposition oxidation, plaque formation, narrowing lumen. Pre-existing independent severity, evident reporting morbidities. Vinciguerra hypothesized system entry into human initiation dysfunction.23 Data UK Biobank demonstrated COVID-19-positive individuals died left ventricular stroke volume, often global longitudinal strain (GLS), compliance (lower aortic distensibility index) survived.24 Whether predisposed early not yet fully understood. it reasonable believe post-COVID-sequelae worsening renal damage, dyslipidemia (altered lipid metabolism) contribute accelerate aging. nerve activity, RAS, ACE-2 expression adverse remodeling arteries, therefore, bidirectional post-COVID seen Even lack physical activity psychological lockdown modulators baseline age comorbidities disease, per se acceleration (arterial sclerosis) development atherosclerosis. Although reports, mentioned earlier, support speculations, proven studies, great public terms detection prevention reducing coronary vulnerable Statin lipid-lowering pleiotropic anti-inflammatory effects.25 statin act main protease inhibitor.26 Some reports use improved survival rate27 although requires validation studies. role drugs colchicine, oxide, heparin explored ongoing studies.28 There appears stiffness/atherosclerosis severity. Preliminary already morphological changes wall. invasion coronavirus damage. should acknowledge opinion piece prepared point view hence hypothesis generating. molecular discussed, still poorly Therefore, larger performed gain information vasculature, particularly developing unsuccessful establishment collaborative projects essential examine consequences reduce Hopefully, prognostic hypertrophy very limited data, ambulatory monitoring focus ​ None. No conflict interest. Sahrai Saeed Giuseppe Mancia conception work. wrote first draft. critically revised intellectual. authors approved final submission.