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  1. Thent ZC, Froemming GRA, Muid SA
    Curr Drug Targets, 2019;20(4):421-430.
    PMID: 30378497 DOI: 10.2174/1389450119666181031124430
    Increasing interest in vascular pseudo-ossification has alarmed the modern atherosclerotic society. High phosphate is one of the key factors in vascular pseudo ossification, also known as vascular calcification. The active process of deposition of the phosphate crystals in vascular tissues results in arterial stiffness. High phosphate condition is mainly observed in chronic kidney disease patients. However, prolonged exposure with high phosphate enriched foods such as canned drinks, dietary foods, etc. can be considered as modifiable risk factors for vascular complication in a population regardless of chronic kidney disease. High intake of vitamin K regulates the vascular calcification by exerting its anti-calcification effect. The changes in serum phosphate and vitamin K levels in a normal individual with high phosphate intake are not well investigated. This review summarised the underlying mechanisms of high phosphate induced vascular pseudo ossification such as vascular transdifferentiation, vascular apoptosis and phosphate uptake by sodium-dependent co-transporters. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google Scholar were searched using the terms 'vitamin K', 'vascular calcification, 'phosphate', 'transdifferentiation' and 'vascular pseudoossification'. Vitamin K certainly activates the matrix GIA protein and inhibits vascular transition and apoptosis in vascular pseudo-ossification. The present view highlighted the possible therapeutic linkage between vitamin K and the disease. Understanding the role of vitamin K will be considered as potent prophylaxis agent against the vascular disease in near future.
    Matched MeSH terms: Vascular Calcification/chemically induced; Vascular Calcification/drug therapy*; Vascular Calcification/metabolism
  2. Choi Y, Chang Y, Ryu S, Cho J, Rampal S, Zhang Y, et al.
    Heart, 2015 May;101(9):686-91.
    PMID: 25732752 DOI: 10.1136/heartjnl-2014-306663
    To investigate the association between regular coffee consumption and the prevalence of coronary artery calcium (CAC) in a large sample of young and middle-aged asymptomatic men and women.
    Matched MeSH terms: Vascular Calcification/epidemiology*
  3. Chang Y, Kim BK, Yun KE, Cho J, Zhang Y, Rampal S, et al.
    J Am Coll Cardiol, 2014 Jun 24;63(24):2679-86.
    PMID: 24794119 DOI: 10.1016/j.jacc.2014.03.042
    The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women.
    Matched MeSH terms: Vascular Calcification/diagnosis*; Vascular Calcification/metabolism*; Vascular Calcification/epidemiology
  4. Choi Y, Chang Y, Ryu S, Cho J, Kim MK, Ahn Y, et al.
    Am J Cardiol, 2015 Aug 15;116(4):520-6.
    PMID: 26073677 DOI: 10.1016/j.amjcard.2015.05.005
    The relation between glycemic index, glycemic load, and subclinical coronary atherosclerosis is unknown. The aim of the study was to evaluate the associations between energy-adjusted glycemic index, glycemic load, and coronary artery calcium (CAC). This study was cross-sectional analysis of 28,429 asymptomatic Korean men and women (mean age 41.4 years) without a history of diabetes or cardiovascular disease. All participants underwent a health screening examination between March 2011 and April 2013, and dietary intake over the preceding year was estimated using a validated food frequency questionnaire. Cardiac computed tomography was used for CAC scoring. The prevalence of detectable CAC (CAC score >0) was 12.4%. In multivariable-adjusted models, the CAC score ratios (95% confidence intervals) comparing the highest to the lowest quintile of glycemic index and glycemic load were 1.74 (1.08 to 2.81; p trend = 0.03) and 3.04 (1.43 to 6.46; p trend = 0.005), respectively. These associations did not differ by clinical subgroups, including the participants at low cardiovascular risk. In conclusion, these findings suggest that high dietary glycemic index and glycemic load were associated with a greater prevalence and degree of CAC, with glycemic load having a stronger association.
    Matched MeSH terms: Vascular Calcification/diagnosis; Vascular Calcification/epidemiology*
  5. Zhang Y, Kim BK, Chang Y, Ryu S, Cho J, Lee WY, et al.
    Arterioscler Thromb Vasc Biol, 2014 Sep;34(9):2128-34.
    PMID: 25060795 DOI: 10.1161/ATVBAHA.114.303889
    OBJECTIVE: Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC).
    APPROACH AND RESULTS: We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone.
    CONCLUSIONS: In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification.
    KEYWORDS: thyroid hormones; thyrotropin; thyroxine; triiodothyronine
    Matched MeSH terms: Vascular Calcification/epidemiology*; Vascular Calcification/radiography
  6. Cainzos-Achirica M, Rampal S, Chang Y, Ryu S, Zhang Y, Zhao D, et al.
    Atherosclerosis, 2015 Aug;241(2):350-6.
    PMID: 26071657 DOI: 10.1016/j.atherosclerosis.2015.05.031
    OBJECTIVE: To evaluate the association between brachial-ankle pulse wave velocity (baPWV), a convenient, non-radiating, readily available measurement of arterial stiffness, and coronary artery calcium (CAC), a reliable marker of coronary atherosclerosis, in a large sample of young and middle-aged asymptomatic adults; and to assess the incremental value of baPWV for detecting prevalent CAC beyond traditional risk factors.
    METHODS: Cross-sectional study of 15,185 asymptomatic Korean adults who voluntarily underwent a comprehensive health screening program including measurement of baPWV and CAC. BaPWV was measured using an oscillometric method with cuffs placed on both arms and ankles. CAC burden was assessed using a multi-detector CT scan and scored following Agatston's method.
    RESULTS: The prevalence of CAC > 0 and CAC > 100 increased across baPWV quintiles. The multivariable-adjusted odds ratios (95% CI) for CAC > 0 comparing baPWV quintiles 2-5 versus quintile 1 were 1.06 (0.87-1.30), 1.24 (1.02-1.50), 1.39 (1.15-1.69) and 1.60 (1.31-1.96), respectively (P trend < 0.001). Similarly, the relative prevalence ratios for CAC > 100 were 1.30 (0.74-2.26), 1.59 (0.93-2.71), 1.74 (1.03-2.94) and 2.59 (1.54-4.36), respectively (P trend < 0.001). For CAC > 100, the area under the ROC curve for baPWV alone was 0.71 (0.68-0.74), and the addition of baPWV to traditional risk factors significantly improved the discrimination and calibration of models for detecting prevalent CAC > 0 and CAC > 100.
    CONCLUSIONS: BaPWV was independently associated with the presence and severity of CAC in a large sample of young and middle-aged asymptomatic adults. BaPWV may be a valuable tool for identifying apparently low-risk individuals with increased burden of coronary atherosclerosis.
    KEYWORDS: Arterial stiffness; Atherosclerosis; Coronary artery calcium; Pulse wave velocity; Subclinical disease
    Matched MeSH terms: Vascular Calcification/diagnosis*; Vascular Calcification/epidemiology; Vascular Calcification/physiopathology
  7. Choi Y, Chang Y, Lee JE, Chun S, Cho J, Sung E, et al.
    Atherosclerosis, 2015 Aug;241(2):305-12.
    PMID: 26062990 DOI: 10.1016/j.atherosclerosis.2015.05.036
    OBJECTIVE:
    The association of egg consumption with subclinical coronary atherosclerosis remains unknown. Our aim was to examine the association between egg consumption and prevalence of coronary artery calcium (CAC).
    METHODS:
    Cross-sectional study of 23,417 asymptomatic adult men and women without a history of cardiovascular disease (CVD) or hypercholesterolemia, who underwent a health screening examination including cardiac computed tomography for CAC scoring and completed a validated food frequency questionnaire at the Kangbuk Samsung Hospital Total Healthcare Centers, South Korea (March 2011-April 2013).
    RESULTS:
    The prevalence of detectable CAC (CAC score > 0) was 11.2%. In multivariable-adjusted models, CAC score ratio (95% confidence interval [CI]) comparing participants eating ≥ 7 eggs/wk to those eating < 1 egg/wk was 1.80 (1.14-2.83; P for trend = 0.003). The multivariable CAC score ratio (95% CI) associated with an increase in consumption of 1 egg/day was 1.54 (1.11-2.14). The positive association seemed to be more pronounced among participants with low vegetable intake (P for interaction = 0.02) and those with high BMI (P for interaction = 0.05). The association was attenuated and no longer significant after further adjustment for dietary cholesterol.
    CONCLUSION:
    Egg consumption was associated with an increased prevalence of subclinical coronary atherosclerosis and with a greater degree of coronary calcification in asymptomatic Korean adults, which may be mediated by dietary cholesterol. The association was particularly pronounced among individuals with low vegetable intake and those with high BMI.
    KEYWORDS:
    Coronary artery calcium score; Coronary artery disease; Egg consumption
    Matched MeSH terms: Vascular Calcification/diagnosis; Vascular Calcification/epidemiology*
  8. Yun KE, Chang Y, Rampal S, Zhang Y, Cho J, Jung HS, et al.
    J Clin Gastroenterol, 2018 07;52(6):508-514.
    PMID: 28471937 DOI: 10.1097/MCG.0000000000000824
    GOALS: Because of shared risk factors between clinically manifest cardiovascular disease and colorectal cancer, we hypothesized the coexistence of subclinical atherosclerosis measured by coronary artery calcium (CAC) and colorectal adenoma (CRA) and that these 2 processes would also share common risk factors.

    BACKGROUND: No study has directly compared the risk factors associated with subclinical coronary atherosclerosis and CRA.

    STUDY: This was a cross-sectional study using multinomial logistic regression analysis of 4859 adults who participated in a health screening examination (2010 to 2011; analysis 2014 to 2015). CAC scores were categorized as 0, 1 to 100, or >100. Colonoscopy results were categorized as absent, low-risk, or high-risk CRA.

    RESULTS: The prevalence of CAC>0, CAC 1 to 100 and >100 was 13.0%, 11.0%, and 2.0%, respectively. The prevalence of any CRA, low-risk CRA, and high-risk CRA was 15.1%, 13.0%, and 2.1%, respectively. The adjusted odds ratios (95% confidence interval) for CAC>0 comparing participants with low-risk and high-risk CRA with those without any CRA were 1.35 (1.06-1.71) and 2.09 (1.29-3.39), respectively. Similarly, the adjusted odds ratios (95% confidence interval) for any CRA comparing participants with CAC 1 to 100 and CAC>100 with those with no CAC were 1.26 (1.00-1.6) and 2.07 (1.31-3.26), respectively. Age, smoking, diabetes, and family history of CRC were significantly associated with both conditions.

    CONCLUSIONS: We observed a graded association between CAC and CRA in apparently healthy individuals. The coexistence of both conditions further emphasizes the need for more evidence of comprehensive approaches to screening and the need to consider the impact of the high risk of coexisting disease in individuals with CAC or CRA, instead of piecemeal approaches restricted to the detection of each disease independently.

    Matched MeSH terms: Vascular Calcification/epidemiology*
  9. Lioufas N, Toussaint ND, Pedagogos E, Elder G, Badve SV, Pascoe E, et al.
    BMJ Open, 2019 02 21;9(2):e024382.
    PMID: 30796122 DOI: 10.1136/bmjopen-2018-024382
    INTRODUCTION: Patients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlled clinical trials to guide management. Positive associations between serum phosphate and fibroblast growth factor 23 (FGF-23) and cardiovascular morbidity and mortality in both the general and CKD populations have resulted in clinical guidelines suggesting that serum phosphate be targeted towards the normal range, although few randomised and placebo-controlled studies have addressed clinical outcomes using interventions to improve phosphate control. Early preventive measures to reduce the development and progression of vascular calcification, left ventricular hypertrophy and arterial stiffness are crucial in patients with CKD.

    METHODS AND ANALYSIS: We outline the rationale and protocol for an international, multicentre, randomised parallel-group trial assessing the impact of the non-calcium-based phosphate binder, lanthanum carbonate, compared with placebo on surrogate markers of cardiovascular disease in a predialysis CKD population-the
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    nd-points (IMPROVE)-CKD study. The primary objective of the IMPROVE-CKD study is to determine if the use of lanthanum carbonate reduces the burden of cardiovascular disease in patients with CKD stages 3b and 4 when compared with placebo. The primary end-point of the study is change in arterial compliance measured by pulse wave velocity over a 96-week period. Secondary outcomes include change in aortic calcification and biochemical parameters of serum phosphate, parathyroid hormone and FGF-23 levels.

    ETHICS AND DISSEMINATION: Ethical approval for the IMPROVE-CKD trial was obtained by each local Institutional Ethics Committee for all 17 participating sites in Australia, New Zealand and Malaysia prior to study commencement. Results of this clinical trial will be published in peer-reviewed journals and presented at conferences.

    TRIAL REGISTRATION NUMBER: ACTRN12610000650099.

    Matched MeSH terms: Vascular Calcification
  10. Nguyen DND, Chilian WM, Zain SM, Daud MF, Pung YF
    Can J Physiol Pharmacol, 2021 Sep;99(9):827-838.
    PMID: 33529092 DOI: 10.1139/cjpp-2020-0581
    Cardiovascular disease (CVD) is among the leading causes of death worldwide. MicroRNAs (miRNAs), regulatory molecules that repress protein expression, have attracted considerable attention in CVD research. The vasculature plays a big role in CVD development and progression and dysregulation of vascular cells underlies the root of many vascular diseases. This review provides a brief introduction of the biogenesis of miRNAs and exosomes, followed by overview of the regulatory mechanisms of miRNAs in vascular smooth muscle cells (VSMCs) intracellular signaling during phenotypic switching, senescence, calcification, and neointimal hyperplasia. Evidence of extracellular signaling of VSMCs and other cells via exosomal and circulating miRNAs is also presented. Lastly, current drawbacks and limitations of miRNA studies in CVD research and potential ways to overcome these disadvantages are discussed in detail. In-depth understanding of VSMC regulation via miRNAs will add substantial knowledge and advance research in diagnosis, disease progression, and (or) miRNA-derived therapeutic approaches in CVD research.
    Matched MeSH terms: Vascular Calcification
  11. Al-Muhaidb SM, Aljebreen AMM, AlZamel ZA, Fathala A
    Coron Artery Dis, 2021 May 01;32(3):179-183.
    PMID: 32769402 DOI: 10.1097/MCA.0000000000000937
    OBJECTIVES: A higher coronary artery calcium score (CACS) is associated with increased coronary artery plaque burden resulting in increased cardiovascular risk. Conversely, the absence of calcium indicates a low risk of cardiovascular events. However, coronary plaque calcification is a late manifestation of atherosclerosis; earlier stages of atherosclerosis present noncalcified plaques (NCPs) A recent study demonstrated that the absence of coronary artery calcification deposit does not preclude obstructive stenosis or the need for revascularization in patients with a high suspicion of coronary artery disease (CAD). Our study aimed to investigate the prevalence of NCP and the severity of coronary artery stenosis in symptomatic patients in our local population who were referred for coronary artery computed tomography angiogram (CCTA) with 0 CACS.

    METHODS: A total of 299 patients who had undergone CACS and CCTA, and had scored zero for coronary artery calcium. Patients included had clinically appropriate indications, mainly chest pain with variable severity with no history of CAD. The presence of CAD risk factors, such as diabetes, hypertension, and smoking, was obtained from reviewing patient charts. The CCTA analysis was performed to evaluate for coronary artery stenosis and the presence of NCP. The severity of stenosis was quantified by visual estimation and divided into 0% stenosis, 1-25% stenosis, 26-50% stenosis, and more than 50% stenosis.

    RESULTS: The prevalence of NCP was 6.4% (19 of the 299). Among the 19 patients with NCP, 52.6% had no identified coronary artery stenosis, 26.3% had less than 25%, and 21% had stenosis between 25 and 50%. None had stenosis greater than 50%. There was a strong association between male sex (P = 0.001), smoking (P = 0.0.004), hypertension, and NCP (P = 0.042), but no association was found between NCP and age or diabetes.

    CONCLUSIONS: In patients with a high clinical suspicion of CAD, the absence of coronary artery calcification does not rule out CAD; up to 6.4% of these patients have early CAD as evidenced by NCP detected by CCTA, and none have more than 50% stenosis, However, future prognostic and long-term follow-up studies are needed to determine prognostic value of NCP in patients with 0 CACS.

    Matched MeSH terms: Vascular Calcification
  12. Chia PL, Earnest A, Lee R, Lim J, Wong CP, Chia YW, et al.
    Ann Acad Med Singap, 2013 Sep;42(9):432-6.
    PMID: 24162317
    INTRODUCTION: In Singapore, the age-standardised event rates of myocardial infarction (MI) are 2- and 3-fold higher for Malays and Indians respectively compared to the Chinese. The objectives of this study were to determine the prevalence and quantity of coronary artery calcification (CAC) and non-calcified plaques across these 3 ethnic groups.

    MATERIALS AND METHODS: This was a retrospective descriptive study. We identified 1041 patients (810 Chinese, 139 Malays, 92 Indians) without previous history of cardiovascular disease who underwent cardiac computed tomography for atypical chest pain evaluation. A cardiologist, who was blinded to the patients' clinical demographics, reviewed all scans. We retrospectively analysed all their case records.

    RESULTS: Overall, Malays were most likely to be active smokers (P = 0.02), Indians had the highest prevalence of diabetes mellitus (P = 0.01) and Chinese had the highest mean age (P <0.0001). The overall prevalence of patients with non-calcified plaques as the only manifestation of sub-clinical coronary artery disease was 2.1%. There was no significant difference in the prevalence of CAC, mean CAC score or prevalence of non-calcified plaques among the 3 ethnic groups. Active smoking, age and hypertension were independent predictors of CAC. Non-calcified plaques were positively associated with male gender, age, dyslipidaemia and diabetes mellitus.

    CONCLUSION: The higher MI rates in Malays and Indians in Singapore cannot be explained by any difference in CAC or non-calcified plaque. More research with prospective follow-up of larger patient populations is necessary to establish if ethnic-specific calibration of CAC measures is needed to adjust for differences among ethnic groups.

    Matched MeSH terms: Vascular Calcification/ethnology*
  13. Chun S, Choi Y, Chang Y, Cho J, Zhang Y, Rampal S, et al.
    Am Heart J, 2016 07;177:17-24.
    PMID: 27297845 DOI: 10.1016/j.ahj.2016.03.018
    BACKGROUND: Sugar-sweetened carbonated beverage consumption has been linked to obesity, metabolic syndrome, type 2 diabetes, and clinically manifest coronary heart disease, but its association with subclinical coronary heart disease remains unclear. We investigated the relationship between sugar-sweetened carbonated beverage consumption and coronary artery calcium (CAC) in a large study of asymptomatic men and women.

    METHODS: This was a cross-sectional study of 22,210 adult men and women who underwent a comprehensive health screening examination between 2011 and 2013 (median age 40 years). Sugar-sweetened carbonated beverage consumption was assessed using a validated food frequency questionnaire, and CAC was measured by cardiac computed tomography. Multivariable-adjusted CAC score ratios and 95% CIs were estimated from robust Tobit regression models for the natural logarithm (CAC score +1).

    RESULTS: The prevalence of detectable CAC (CAC score >0) was 11.7% (n = 2,604). After adjustment for age; sex; center; year of screening examination; education level; physical activity; smoking; alcohol intake; family history of cardiovascular disease; history of hypertension; history of hypercholesterolemia; and intake of total energy, fruits, vegetables, and red and processed meats, only the highest category of sugar-sweetened carbonated beverage consumption was associated with an increased CAC score compared with the lowest consumption category. The multivariable-adjusted CAC ratio comparing participants who consumed ≥5 sugar-sweetened carbonated beverages per week with nondrinkers was 1.70 (95% CI, 1.03-2.81). This association did not differ by clinical subgroup, including participants at low cardiovascular risk.

    CONCLUSION: Our findings suggest that high levels of sugar-sweetened carbonated beverage consumption are associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.

    Matched MeSH terms: Vascular Calcification/epidemiology*
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