Heart Disease - Comorbidities

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Heart Disease - Comorbidities

Post by wendy »

Heart Disease
© 2020 PFPC


"The biggest risk factor for dying of coronavirus is cardiovascular (heart) disease, with a death rate of 10.5%. But we don’t yet know why."

https://theconversation.com/why-are-old ... rus-133770


Acute cardiac injury...is the most commonly reported cardiac abnormality in COVID-19 patients.

(Bansal, 2020).

Bansal M - "Cardiovascular disease and COVID-19" Diabetes Metab Syndr 14(3):247-250 (2020) doi: 10.1016/j.dsx.2020.03.013. Epub 2020 Mar 25. PMID: 32247212; PMCID: PMC7102662.

Recently, focus on treatment-related research in COVID-19 has been renewed on the ACE2 receptor, the receptor by which the coronavirus SARS-CoV-2 enters the cell. [By March 2020, only one of the drugs in clinical trials had considered the renin-angiotensin system (RAS) (Malha et al., 2020).]

"Given the functions of ACE2 in the cardiovascular system, the importance of angiotensin-directed pharmacology in cardiovascular
disease and the apparent propensity for severe illness among patients with COVID-19 with cardiovascular comorbidity, the ACE2 molecule has been the subject of much attention (18). Indeed, major clinical societies have issued consensus statements on the use of ACE inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) in the setting of the COVID-19 pandemic, as discussed later (19). Angiotensin-Converting enzyme 2 (ACE2) is a single-pass transmembrane protein with protease activity that cleaves the vasoconstrictor angiotensin II into the vasodilator angiotensin 1-7 (20-23). In doing so, it functions as a counter-regulatory enzyme to the functions of ACE1, which generates angiotensin II (20). In humans, the protein has a broad pattern of expression and has been found in the lung epithelium (in particular the type II pneumocyte), the myocardium, the endothelium, the GI tract, bone marrow, kidneys and spleen among other tissues; potentially explaining the multi-organ injury observed with SARS-CoV2 infection (24)."

(Atri et al., 2020)

Atri D, Siddiqi HK, Lang J, Nauffal V, Morrow DA, Bohula EA - "COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies" JACC Basic Transl Sci Apr 10 (2020) doi: 10.1016/j.jacbts.2020.04.002. Epub ahead of print. PMID: 32292848; PMCID: PMC7151394.
https://www.ncbi.nlm.nih.gov/pmc/articl ... f/main.pdf


Fluoride, by interfering with thyroid hormone metabolism, may affect many factors associated with heart disease. A few are discussed in more detail in this forum, such as cardiac troponins. See: viewtopic.php?f=66&t=1883

The effects of fluoride on the heart have been studied since the 1950s.

Adali MK, Varol E, Aksoy F, Icli A, Ersoy IH, Ozaydin M, Erdogan D, Dogan A - "Impaired heart rate recovery in patients with endemic fluorosis" Biol Trace Elem Res 152(3):310-5 (2013) doi: 10.1007/s12011-013-9627-6. Epub 2013 Feb 16. PMID: 23417496.

"Endemic fluorosis is a risk factor for decrease in calcium and FT4 levels, increase in sodium levels and QT prolongation. These findings might be related with some cardiovascular system dysfunctions such as arrhythmias or syncope. Subjects with fluorosis should be monitored in terms of long QT and QTc intervals."

(Karademir et al., 2011)

Karademir S, Akçam M, Kuybulu AE, Olgar S, Oktem F - "Effects of fluorosis on QT dispersion, heart rate variability and echocardiographic parameters in children" Anadolu Kardiyol Derg 11(2):150-5 (2011) doi: 10.5152/akd.2011.038. Epub 2011 Feb 23. PMID: 21342861

"We have shown that chronic fluorosis patients had left ventricular diastolic and global dysfunctions."

(Varol et al., 2010)

Varol E, Akcay S, Ersoy IH, Koroglu BK, Varol S - "Impact of chronic fluorosis on left ventricular diastolic and global functions" Sci Total Environ 408(11):2295-8 (2010) doi: 10.1016/j.scitotenv.2010.02.011. Epub 2010 Mar 5. PMID: 20206377


Of course, the involvement of Gq/11 in heart disease is well established. The Angiotensin 1 - AT(1)R is one the most-studied receptors and signals through Gq/11 to transduce signals on lymphocytes in autoimmune-regulated cardiomyopathy and hypertension (Zhang & Shi, 2016).

Tilley (2011) wrote an excellent review of Gq/11 involvement in the heart.

Tilley DG - "G protein-dependent and G protein-independent signaling pathways and their impact on cardiac function" Circ Res 109(2):217-30 (2011) doi: 10.1161/CIRCRESAHA.110.231225. PMID: 21737817; PMCID: PMC3138127


The involvement of thyroid hormones in cardiac disease is also well establised.

"In general, consistent with prior work (8), AF (25–31), osteoporosis (32–39), and cancer (40–43) were associated with higher thyroid function that was defined by using TSH and/or thyroid hormone levels, across and beyond the reference range, and steatohepatitis (44–46) and other features of the metabolic syndrome (19,47–66) were associated with lower thyroid function. Both high and low thyroid function, as compared with mid-range thyroid function, were associated with clinical and pathological features of cognitive decline (26,67–75), frailty (76–79), total/cardiovascular mortality (26,80–88), cardiac physiology (89), cardiac disease (apart from AF) (26,31,67,83–85,88,90,91), and pregnancy outcomes (92–99)."

(Fitzgerald et al., 2020)

Fitzgerald SP, Bean NG, Falhammar H, Tuke J - "Clinical Parameters Are More Likely to Be Associated with Thyroid Hormone Levels than with Thyrotropin Levels: A Systematic Review and Meta-analysis" Thyroid (2020) doi: 10.1089/thy.2019.0535. Epub ahead of print. PMID: 32349628

"Hypo- and hyperthyroidism were associated with worse clinical outcomes in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)."

Perez AC, Jhund PS, Stott DJ, Gullestad L, Cleland JG, van Veldhuisen DJ, Wikstrand J, Kjekshus J, McMurray JJ - "Thyroid-stimulating hormone and clinical outcomes: the CORONA trial (controlled rosuvastatin multinational study in heart failure)" JACC Heart Fail 2(1):35-40 (2014) doi: 10.1016/j.jchf.2013.07.008. Epub 2014 Jan 25. PMID: 24622117

"The association with death is significant when TSH >10 mIU/L."
(Iacoviello et al., 2020)

Iacoviello M, Parisi G, Gioia MI, Grande D, Rizzo C, Guida P, Lisi F, Giagulli VA, Licchelli B, Di Serio F, Guastamacchia E, Triggiani V - "Thyroid Disorders and Prognosis in Chronic Heart Failure: A Long-Term Follow-Up Study" Endocr Metab Immune Disord Drug Targets 20(3):437-445 (2020) doi: 10.2174/1871530319666191018134524. PMID: 31656160

SEE ALSO: Atherosclerosis
SEE ALSO: Cardiac Troponins. viewtopic.php?f=66&t=1883

Kaviyarasi Renu, Prasanna PL, Abilash VG - "Coronaviruses pathogenesis, comorbidities and multi-organ damage - A review" Life Sci 117839 (2020) doi: 10.1016/j.lfs.2020.117839. Epub ahead of print. PMID: 32450165
https://www.sciencedirect.com/science/a ... via%3Dihub

Malha L, Mueller FB, Pecker MS, Mann SJ, August P, Feig PU - "COVID-19 and the Renin-Angiotensin System" Kidney Int Rep 5(5):563–5 (2020) doi: 10.1016/j.ekir.2020.03.024. Epub ahead of print. PMID: 32292865; PMCID: PMC7118533.

Zaim S, Chong JH, Sankaranarayanan V, Harky A - "COVID-19 and Multiorgan Response" Curr Probl Cardiol 100618 (2020) doi: 10.1016/j.cpcardiol.2020.100618. Epub ahead of print. PMID: 32439197; PMCID: PMC7187881.

Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS - "Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target" Intensive Care Med 46(4):586-590 (2020) doi: 10.1007/s00134-020-05985-9. Epub 2020 Mar 3. PMID: 32125455; PMCID: PMC7079879

Zhang Lu, Shi Guixiu - "Gq-Coupled Receptors in Autoimmunity" Journal of Immunology Research (2016)
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