scholarly journals Pathophysiological and clinical significance of mineral homeostasis disorders in the development of cardiovascular disease

2021 ◽  
Vol 6 (2) ◽  
pp. 82-102
Author(s):  
A. G. Kutikhin
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Death ◽  
Therapeutic Interventions ◽  
Major Adverse Cardiovascular Events ◽  
Formation Mechanisms ◽  
Kidney Transplant Recipients ◽  
Mesenchymal Transition ◽  
Mineral Homeostasis ◽  
Calciprotein Particles

A growing incidence, prevalence, morbidity and mortality from cardiovascular disease dictate an urgent need in identification of its risk factors and their pathogenetic links with coronary artery disease and stroke. Aging of the population is inevitably associated with an increasing prevalence of comorbid conditions. Among them are disorders of mineral homeostasis which, often being neglected, are clearly associated with major adverse cardiovascular events and cardiovascular death. Maintenance of mineral homeostasis in the human body is largely dependent on the formation of calciprotein particles (CPPs) which arise in the blood upon the binding of a mineral chaperone fetuin-A to nascent calcium phosphate crystals, thereby aggregating excessive calcium (Ca2+) and phosphate (PO4 3-), removing them from the bloodstream and preventing extraskeletal calcification. During the circulation, CPPs are internalised by arterial endothelial cells and provoke endothelial dysfunction through endothelial activation, endothelialto-mesenchymal transition and impairment of endothelial mechanotransduction. Animal studies demonstrated that regular intravenous injections of CPPs lead to intimal hyperplasia and adventitial/perivascular inflammation in the absence of any other cardiovascular risk factors, indicating pathophysiological importance of CPPs for cardiovascular disease. Further, a number of clinical studies suggested an association of an augmented serum calcification propensity or elevated CPP count with arterial hypertension, myocardial infarction, chronic brain ischemia, ischemic stroke and cardiovascular death in patients with chronic kidney disease (including those with end-stage renal disease as well as kidney transplant recipients) and individuals with a preserved renal function. Here, we critically discuss the pathophysiological consequences of CPP formation, mechanisms of their pathogenic effects, and potential therapeutic interventions. 

scholarly journals Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation

2021 ◽  
Vol 22 (22) ◽  
pp. 12458
Author(s):  
Daria K. Shishkova ◽  
Elena A. Velikanova ◽  
Leo A. Bogdanov ◽  
Maxim Yu. Sinitsky ◽  
Alexander E. Kostyunin ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Leukocyte Adhesion ◽  
Binding Capacity ◽  
Vascular Inflammation ◽  
Mechanistic Explanation ◽  
High Serum ◽  
Mesenchymal Transition ◽  
Mineral Homeostasis ◽  
Calciprotein Particles

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

scholarly journals Post-Transplant Cardiovascular Disease

2021 ◽  
pp. CJN.00520121
Author(s):  
Kelly A. Birdwell ◽  
Meyeon Park
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Kidney Transplant ◽  
Optimal Strategies ◽  
Future Research ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Treatment And Prevention ◽  
Artery Disease

Cardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.

scholarly journals Increased Plasma Apolipoprotein C-III Concentration Independently Predicts Cardiovascular Mortality: The Hoorn Study

2008 ◽  
Vol 54 (8) ◽  
pp. 1325-1330 ◽  
Author(s):  
Peter G Scheffer ◽  
Tom Teerlink ◽  
Jacqueline M Dekker ◽  
Griët Bos ◽  
Giel Nijpels ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Mortality ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cardiovascular Death ◽  
Apolipoprotein C ◽  
General Population Cohort ◽  
High Concentrations ◽  
Traditional Risk Factors

Abstract Background: Hypertriglyceridemia is a cardiovascular risk factor. Apolipoprotein C-III (apoC-III) is an important determinant of the catabolic rate of triglyceride-rich lipoproteins. The aim of this study was to investigate the prognostic value of plasma apoC-III concentrations for cardiovascular mortality. Methods: We performed this prospective study in 2244 subjects (ages 49–77 years) who participated in the Hoorn Study. During a mean follow-up of 15 years, 504 individuals died: 231 of cardiovascular disease, 180 of cancer, and 93 of other causes. Cardiovascular disease risk factors and plasma apoC-III concentrations were measured at baseline. Results: The age- and sex-adjusted plasma apoC-III concentration was prospectively associated with cardiovascular mortality (P < 0.001). After adjustment for traditional risk factors, including fasting triglycerides, the hazard ratio (95% CI) for cardiovascular death between the highest and the lowest quartile of apoC-III was 1.85 (1.02–3.38). High concentrations of apoC-III did not appear to be associated with noncardiovascular mortality. Conclusions: In this general population cohort, a high apoC-III concentration in plasma, independently of fasting triglycerides and other traditional risk factors, predicts cardiovascular mortality.

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients

2018 ◽  
Vol 48 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Andrew Bostom ◽  
Andreas Pasch ◽  
Tracy Madsen ◽  
Mary B. Roberts ◽  
Nora Franceschini ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Kidney Transplant ◽  
Vascular Calcification ◽  
Lipid Lowering ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cvd Risk ◽  
Effect Modifier ◽  
Fetuin A ◽  
Calciprotein Particles

Background: “T50,” shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. Methods: The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization. Results: During a median surveillance of 2.18-years, 311 incident or recurrent CVD events occurred. Shorter T50 (minutes) or reduced fetuin-A concentrations (g/L) were associated with CVD after adjustment for treatment assignment, systolic blood pressure, age, sex, race, preexisting CVD and diabetes, smoking, body mass index, total cholesterol/HDL cholesterol, kidney allograft vintage and type, calcineurin inhibitor, or lipid-lowering drug use, estimated glomerular filtration rate, and urinary albumin/creatinine: tertile 1 (lowest) to tertile 3 (highest) comparisons, T50, (hazard ratio [HR] 1.86; 95% CI 1.20–2.89); fetuin-A, (HR 2.25; 95% CI 1.38–3.69). Elevated high sensitivity c-reactive protein (hsCRP) was an effect modifier of both these associations. Conclusions: Shortened T50, as well as reduced fetuin-A levels, ostensible promoters of vascular calcification, remained associated with greater risk for CVD outcomes, after adjustment for major CVD risk factors, measures of kidney function and damage, and KTR clinical characteristics and demographics, in a large, multiethnic cohort of long-term KTRs. Increased hsCRP was an effect modifier of these CVD risk associations.

P3639Vascular endothelial growth factor-C and mortality in patients with suspected but no history of coronary heart disease: a subanalysis of the ANOX study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Unoki ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
All Cause Mortality ◽  
History Of ◽  
Factor C ◽  
Endothelial Growth Factor

Abstract Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. Recently, we demonstrated that serum levels of vascular endothelial growth factor-C (VEGF-C), a central player of lymphangiogenesis, are inversely and independently associated with the risk of all-cause mortality in patients with suspected or known coronary heart disease (CHD). However, the prognostic value of VEGF-C in patients with suspected but no history of CHD is still unclear. Methods Serum VEGF-C levels were measured in 1,717 patients with suspected but no history of CHD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 161 patients died from any cause, 50 died from cardiovascular disease, and 104 developed MACE. After adjustment for established risk factors, VEGF-C levels were significantly and inversely associated with all-cause death (hazard ratio [HR] for 1-SD increase, 0.69; 95% confidence interval [CI], 0.58–0.83) and cardiovascular death (HR, 0.72; 95% CI, 0.52–0.998), but not with MACE (HR, 0.91; 95% CI, 0.74–1.13). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-C levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.282; 95% CI, 0.121–0.443; P<0.001; integrated discrimination improvement [IDI], 0.009; 95% CI, 0.003–0.016; P=0.005), but not that of cardiovascular death (NRI, 0.178; 95% CI, r=−0.103–0.458; P=0.214; IDI, 0.004; 95% CI, r=−0.002–0.009; P=0.194) or MACE (NRI, 0.037; 95% CI, r=−0.162–0.235; P=0.717; IDI, 0.000; 95% CI, r=−0.0004–0.0005; P=0.872). Conclusions In patients with suspected but no history of CHD undergoing elective coronary angiography, a low VEGF-C value may predict all-cause mortality independent of established risk factors and cardiovascular biomarkers. Acknowledgement/Funding The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization

scholarly journals Mortality of Patients with Cushing’s Disease

2020 ◽  
Author(s):  
Georgia Ntali ◽  
Osamah Hakami ◽  
Milanka Wattegama ◽  
Shahzada Ahmed ◽  
Niki Karavitaki
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Pituitary Adenoma ◽  
Early Diagnosis ◽  
Cushing’S Disease ◽  
Rare Condition ◽  
Therapeutic Interventions ◽  
Cushing's Disease ◽  
Close Monitoring

AbstractCushing’s disease is a rare condition of cortisol excess attributed to a pituitary adenoma with an annual incidence of 1.2–2.4 cases per million population. It is associated with several co-morbidities leading to increased mortality predominantly due to cardiovascular disease. Despite the advances in its diagnosis and management, survival can be compromised even after apparent successful treatment. Minimizing the duration and extent of exposure to hypercortisolaemia by early diagnosis and rapid, effective therapeutic interventions, as well as close monitoring and aggressive control of cardiovascular risk factors are vital for improving outcomes of the patients.

scholarly journals Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21

2015 ◽  
Vol 309 (6) ◽  
pp. H1029-H1038 ◽  
Author(s):  
Eleni M. Domouzoglou ◽  
Katerina K. Naka ◽  
Antonios P. Vlahos ◽  
Michail I. Papafaklis ◽  
Lampros K. Michalis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Growth Factors ◽  
Cardiovascular Risk ◽  
Fibroblast Growth Factors ◽  
Serum Levels ◽  
Cardiovascular Death ◽  
Metabolic Effects ◽  
Fibroblast Growth ◽  
Metabolic Role

Early detection of risk factors for enhanced primary prevention and novel therapies for treating the chronic consequences of cardiovascular disease are of the utmost importance for reducing morbidity. Recently, fibroblast growth factors (FGFs) have been intensively studied as potential new molecules in the prevention and treatment of cardiovascular disease mainly attributable to metabolic effects and angiogenic actions. Members of the endocrine FGF family have been shown to increase metabolic rate, decrease adiposity, and restore glucose homeostasis, suggesting a multiple metabolic role. Serum levels of FGFs have been associated with established cardiovascular risk factors as well as with the severity and extent of coronary artery disease and could be useful for prediction of cardiovascular death. Furthermore, preclinical investigations and clinical trials have tested FGF administration for therapeutic angiogenesis in ischemic vascular disease, demonstrating a potential role in improving angina and limb function. FGF21 has lately emerged as a potent metabolic regulator with multiple effects that ultimately improve the lipoprotein profile. Early studies show that FGF21 is associated with the presence of atherosclerosis and may play a protective role against plaque formation by improving endothelial function. The present review highlights recent investigations suggesting that FGFs, in particular FGF21, may be useful as markers of cardiovascular risk and may also serve as protective/therapeutic agents in cardiovascular disease.

scholarly journals Vasoplegia after cardiopulmonary bypass: A narrative review of pathophysiology and emerging targeted therapies

2020 ◽  
Vol 8 ◽  
pp. 205031212093546
Author(s):  
Theresa J Barnes ◽  
Maxwell A Hockstein ◽  
Craig S Jabaley
Keyword(s):  
Nitric Oxide ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiopulmonary Bypass ◽  
The United States ◽  
Narrative Review ◽  
Therapeutic Interventions ◽  
Related Disease ◽  
Disease States ◽  
Pathophysiologic Mechanisms

Cardiovascular disease remains the leading cause of death in the United States, and cardiopulmonary bypass is a cornerstone in the surgical management of many related disease states. Pathophysiologic changes associated both with extracorporeal circulation and shock can beget a syndrome of low systemic vascular resistance paired with relatively preserved cardiac output, termed vasoplegia. While increased vasopressor requirements accompany vasoplegia, related pathophysiologic mechanisms may also lead to true catecholamine resistance, which is associated with further heightened mortality. The introduction of a second non-catecholamine vasopressor, angiotensin II, and non-specific nitric oxide scavengers offers potential means by which to manage this challenging phenomenon. This narrative review addresses both the definition, risk factors, and pathophysiology of vasoplegia and potential therapeutic interventions.

scholarly journals Genetic Risk Factors for CVD in Type 1 Diabetes: the DCCT/EDIC Study

2021 ◽  
Author(s):  
Ionut Bebu ◽  
Sareh Keshavarzi ◽  
Xiaoyu Gao ◽  
Barbara H. Braffett ◽  
Angelo J. Canty ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Genetic Factors ◽  
Risk Scores ◽  
Major Adverse Cardiovascular Events ◽  
Cvd Risk ◽  
Individual Snps

<b>Background</b> The role of genetic factors on the risk of cardiovascular disease (CVD) risk in type 1 diabetes remains unknown. We therefore examined whether previously identified genetic factors for coronary artery disease (CAD) are associated with the risk of CVD <i>above and beyond</i> established demographic and clinical factors in The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p><b>Methods</b> Polygenic risk scores (PRS) and individual genetic variants identified in previous studies were obtained from genome-wide genotyping performed in 1371 DCCT/EDIC participants. Two composite CVD outcomes were considered: major adverse cardiovascular events (MACE) (CVD death or non-fatal myocardial infarction or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure). Cox proportional hazards models assessed the association between the genetic factors and the risk of CVD when adjusted for other factors (including age, lipids, blood pressure and glycemia). </p> <p><b>Results</b> CAD PRS was strongly associated with the subsequent risk of any-CVD (42% and 38% higher risk per 1 standard deviation (SD) increase in unadjusted and fully adjusted models, respectively, p<0.0001), and with the risk of MACE (50% and 40% higher risk per 1SD increase in unadjusted and fully adjusted models, respectively, p<0.0001). Several individual SNPs were also nominally associated with the risk of any-CVD and MACE.</p> <p><b>Conclusions </b>Genetic factors are associated with the risk of subsequent cardiovascular disease in individuals with type 1 diabetes, above and beyond the effect of established risk factors such as age, lipids, blood pressure and glycemia. </p>

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