|Year : 2022 | Volume
| Issue : 3 | Page : 256-259
Serum calcium levels and its association with coronary artery disease
Mansi A Patel, Sachin Ratanlal Agrawal, Sourya Acharya, Sunil Kumar
Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences and Research (Deemed to be University), Wardha, Maharashtra, India
|Date of Submission||07-Jun-2022|
|Date of Acceptance||27-Aug-2022|
|Date of Web Publication||27-Dec-2022|
Dr. Mansi A Patel
Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences and Research (Deemed to be University), Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Thousands of people took part in prospective studies lasting up to 30 years, and the results showed that circulating calcium is a risk factor for vascular disease. Other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index may partially mediate these relationships, but serum calcium appears to have a residual independent influence. Polymorphisms in calcium-sensing receptors connected to small elevations in serum calcium have also been linked to cardiovascular disease, suggesting that calcium is a causative component. Calcium supplements have been shown to increase mortality and/or accelerate vascular disease in dialysis patients and those with less severe renal failure, and meta-analyses of trials in adults without overt renal disease imply a similar effect. A strong interaction between baseline calcium supplement use and the effect of calcium randomization hampered the interpretation of the largest research. The fact that the study only looked at calcium-deficient people highlights the dangers that are always present. Observational studies of dietary calcium have not consistently demonstrated that it is deleterious to cardiovascular health, albeit exceptionally high or extremely low intakes may be harmful. As a result, eating calcium rather than taking supplements should be encouraged. The current systematic review addresses serum calcium levels and their relationship with coronary artery disease using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. For studies published through December 2021, electronic and manual data resources were reviewed using the following databases: PubMed/MEDLINE, Embase, ScienceDirect, Cochrane Library. The findings were filtered to exclude studies that were written in English.
Keywords: Polymorphism, renal, vascular
|How to cite this article:|
Patel MA, Agrawal SR, Acharya S, Kumar S. Serum calcium levels and its association with coronary artery disease. J Sci Soc 2022;49:256-9
| Introduction|| |
Acute coronary syndrome, the most visible and unpredictable manifestation of coronary artery disease (CAD), is essentially the disease's fatal consequence. Stable angina, which is characterized by a disparity in myocardial oxygen demand and supply, is a common clinical manifestation of CAD. Smoking, poor diet, lack of physical activity, dyslipidemia, obesity, hypertension, and diabetes mellitus are all known risk factors for CAD. According to accumulating data from animal and human research, Vitamin D insufficiency may be a crucial trigger in the development of CAD. Given the complexity of the CAD problem, more study into other risk factors that could serve as feasible therapy targets for the disease's management and prevention is required.
| Search Strategy|| |
The words serum calcium were used in the search technique on multiple databases. The terms “serum calcium” (All Fields) AND “serum calcium” (MeSH Terms) OR “serum calcium” (All Fields) AND “coronary artery disease” (MeSH Term) were used in the PubMed/MEDLINE literature search. On the internet, the abovementioned words (serum calcium) were employed in a search strategy on the Cochrane Library, the database for systematic review [Chart 1].
Calcium-sensing receptors are found on the surface of many cells, and evidence suggests that calcium ion concentrations in the extracellular fluid have a direct impact on cell activity (e.g., parathyroid, renal tubule, and many more). Calcium aids muscle contraction, particularly in the heart. Calcium chelators (citrate and ethylenediaminetetraacetic acid) are the most commonly used anticoagulants in blood collection because calcium is a cofactor for various enzymes and is essential for blood coagulation. Bone is a form of connective tissue made up primarily of type I collagen.
When osteoblasts generate the collagen matrix, calcium and phosphate ions are deposited between collagen fibers, resulting in hydroxyapatite crystals. Bone is a composite material because collagen provides tensile strength and hydroxyapatite provides compressive strength. The balance of osteoblasts' bone-forming activity and osteoclasts' bone-resorbing activity determines bone mass. Although calcium deficit has no direct effect on bone growth, severe calcium insufficiency can impede osteoid mineralization, resulting in hypocalcemia. The significance of calcium in vascular health is less clear. The role of calcium in smooth muscle contraction has already been discussed, as has its importance in heart electrophysiology and myocardial function. Vascular smooth muscle cells and platelets both include calcium-sensing receptors.
Calcium buildup in the veins is a typical indication of vascular disease and has been related to serious cardiovascular repercussions. Calcium buildup in other soft tissues (such as the kidneys or muscles) impairs tissue function, hence a complex system of mineralization inhibitors is in place to avoid this (such as pyrophosphate, fetuin-A, and matrix GLA protein). Tissue-specific targeting of mineralization management is clearly essential to boost the mineralization of bone while restricting the mineralization of all other tissues. The effectiveness of these systems deteriorates with age, especially in the vascular system. Furthermore, blood calcium levels appear to influence the course of vascular disease.,,
In hemodynamically controlled research, there are significant anecdotal and observational data that suggest a link between hypocalcemia and the development of QTc prolongation, severe arrhythmias, left ventricular systolic dysfunction, and clinical symptoms of heart failure. Hypocalcemia rarely occurs in isolation in normal clinical practice, and a variety of pathologic diseases, drugs, and iatrogenic causes may all be contributing to the development of QTc prolongation and heart failure. Nonetheless, certain substantial clinical trials imply that hypocalcemia is a causative factor in the development of reversible heart failure, which warrants more investigation.
It is widely known that calcium plays a crucial role in the sequence of cardiac excitation-contraction coupling and relaxation. At the same hand, new research has shown that people with hypocalcemia-induced reversible cardiomyopathy and no underlying myocardial disease can develop hypocalcemia heart failure, and that if serum calcium levels are corrected, left ventricular systolic dysfunction can be reversed.
Several studies have connected increased baseline blood calcium levels to the development of calcified coronary atherosclerotic plaque as well as an independent and prospective risk factor for new-onset myocardial infarction (MI) in those with cardiovascular risk factors.
Genetic polymorphisms with a specific effect on putative risk variables could be used to study correlations with explicit outcomes. Mendelian randomization eliminates some of the limitations of observational research (because genetic data should be free of confounding variables) and is unaffected by sickness state, reducing reverse causation bias. As a result, genetic variants that affect serum calcium levels could be utilized as instrumental variables (proxies) to analyze the link between rising blood calcium over time and the risk of CAD.
Only men who consumed more than 1400 mg of calcium per day were shown to have an increased risk of all-cause mortality in a recent prospective cohort study. Calcium supplementation was linked to a lower risk of stroke in people with a low dietary calcium intake (700 mg/d), but an increased risk of stroke in people with a high dietary calcium intake (1000 mg/d), according to a meta-analysis. These findings show that the advantages of calcium supplementation are likely to vary with demographic. As a result, more research is needed to see if proper calcium supplement therapy, especially for CAD patients with low blood calcium levels, will improve their prognosis.,,
In addition to serum calcium, phosphorus, and albumin levels, a multiple regression analysis using age, gender, smoking, diabetes, hypertension, hyperlipidemia, ethnicity, and family history as predictor variables revealed that serum albumin has an independent negative association with angiographic severity of CAD, while serum phosphorus has an independent positive association.
According to several clinical studies, higher serum phosphorus levels and the calcium–phosphorus product in patients with CKD are linked to an increase in carotid atherosclerosis and coronary calcification cross-sectionally, as well as an increased risk of all-cause mortality and cardiovascular disease (CVD) death rates longitudinally.
Calcium in the blood is thought to play a role in the pathogenesis of CVD. This begs the question of whether calcium supplementation or dietary calcium intake affects vascular health. It is common to test blood calcium levels while fasted and conclude that diet and supplement use have no effect on circulating calcium levels. Studies conducted immediately after calcium delivery, on the other hand, reveal total calcium increases ranging from 0.05 to 0.15 mmol/L, depending on the calcium source and the dosage provided.
One of the side effects of coronary angiography is a sudden and prolonged reduction in blood pressure. This could be because the radiopaque chemicals' carrier contains calcium-chelating agents. Low amounts of ambient calcium have been associated with decreased cardiac contractility and, in extreme cases, electromechanical dissociation. After intracoronary injection of the contrast agent, simultaneous measurements of the radial artery and coronary sinus ionized calcium levels in nine persons revealed a drop in the amount of ionized calcium in the coronary sinus, consistent with a decrease in myocardial contractility. In arteriosclerotic individuals, the reduction in ionized calcium was more pronounced and prolonged, with some reaching levels that, if chronic, might lead to electromechanical dissociation.
Despite evidence of antihypertensive drug efficacy in the treatment of hypertension, the safety and efficacy of antihypertensive drugs for CAD has only been confirmed by subgroup analysis in significant studies.
A multimodal strategy that includes angiotensin-converting enzyme inhibitor therapy for patients with heart failure, diabetes, or renal impairment can achieve lower blood pressure objectives in the majority of hypertensive CAD patients. In clinically stable CAD patients who require blood pressure treatment, the clinical equivalence of the calcium antagonist strategy (CAS) and the non-CAS (NCAS) groups in terms of preventing death, MI, or stroke justifies the use of either technique. When determining which medication classes to use in particular CAD patients, additional characteristics such as unpleasant experiences, a history of heart failure, diabetes risk, and the physician's best judgment should be taken into account. Further research is needed to see if a CAS can delay the onset of a diabetes diagnosis as compared to an NCAS.
| Conclusion|| |
The basic mechanisms underlying the connection between baseline blood calcium levels and CAD mortality are yet unclear. The electrical function of the heart can be disrupted by a calcium shortage in the blood. Low blood calcium levels may induce cardiomyocyte calcium channels to stay open longer, extending the cardiac action potential plateau duration, a well-known cause of death. Calcium deficiency can harm vascular smooth muscle cells, elevate blood pressure, and disturb lipid metabolism, all of which can worsen CVD and the prognosis of CAD patients. Calcium supplementation, alone or in conjunction with Vitamin D, has been demonstrated in numerous trials to have potential effects on cardiovascular events, while the findings are still controversial and insufficient to draw definite conclusions.
Risk variables have been demonstrated to be effective therapy targets; however, they are poor indicators of risk. Traditional risk scores can be used to predict future coronary heart disease occurrences and can be used as a starting point for wide risk classification. However, there is a large difference between conventional risk and true atherosclerosis burden, with atherosclerosis onus driving the majority of event rates. Serum biomarkers have failed to provide any clinically significant information to the Framingham Risk Score (FRS), and even when combined, they fall short of atherosclerosis imaging in terms of prognostic usefulness.
Are we, as doctors, willing to develop therapeutic methods based on risk algorithms with limited precision and integration? Because the efficacy of medication in an asymptomatic patient must overcome the stress of the probable threat, the decision to medicate a patient for treatment and prevention must be taken with prudence. In this case, coronary artery calcium (CAC) provides a personalized risk assessment and may identify those who are likely to benefit the most and least from treatment. According to new research, CAC may improve long-term compliance with aspirin, exercise, diet, and statin medication. Doctors must empower their patients with the most accurate risk prediction tools available when potentially life-changing treatment decisions are at stake, and subclinical atherosclerosis assessment with CAC is currently superior to any combination of risk variables and blood biomarkers.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Aggarwal R, Akhthar T, Jain SK. Coronary artery disease and its association with Vitamin D deficiency. J Midlife Health 2016;7:56-60.
Newman DB, Fidahussein SS, Kashiwagi DT, Kennel KA, Kashani KB, Wang Z, et al
. Reversible cardiac dysfunction associated with hypocalcemia: A systematic review and meta-analysis of individual patient data. Heart Fail Rev 2014;19:199-205.
Wang Y, Ma H, Hao X, Yang J, Chen Q, Lu L, et al
. Low serum calcium is associated with left ventricular systolic dysfunction in a Chinese population with coronary artery disease. Sci Rep 2016;6:22283.
Larsson SC, Burgess S, Michaëlsson K. Association of genetic variants related to serum calcium levels with coronary artery disease and myocardial infarction. JAMA 2017;318:371-80.
Wang M, Yan S, Peng Y, Shi Y, Tsauo JY, Chen M. Serum calcium levels correlates with coronary artery disease outcomes. Open Med (Wars) 2020;15:1128-36.
Narang R, Ridout D, Nonis C, Kooner JS. Serum calcium, phosphorus and albumin levels in relation to the angiographic severity of coronary artery disease. Int J Cardiol 1997;60:73-9.
Wang X, Chen H, Ouyang Y, Liu J, Zhao G, Bao W, et al
. Dietary calcium intake and mortality risk from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. 2014;12:158.
Dhingra R, Sullivan LM, Fox CS, Wang TJ, D'Agostino RB Sr., Gaziano JM, et al.
Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 2007;167:879-85.
Nakamura S, Ishibashi-Ueda H, Niizuma S, Yoshihara F, Horio T, Kawano Y. Coronary calcification in patients with chronic kidney disease and coronary artery disease. Clin J Am Soc Nephrol 2009;4:1892-900.
Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, et al.
A calcium antagonist vs. a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): A randomized controlled trial. JAMA 2003;290:2805-16.
Blaha MJ, Silverman MG, Budoff MJ. Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease? Clinical risk scores are not sufficient to define primary prevention treatment strategies among asymptomatic patients. Circ Cardiovasc Imaging 2014;7:398-408.
Gu X, Ding X, Sun H, Chen N, Liu D, Sun D, et al.
Usefulness of serum calcium in the risk stratification of midterm mortality among patients with acute coronary syndrome. Biomed Res Int 2019;2019:9542054.
Grandi E, Pasqualini FS, Pes C, Corsi C, Zaza A, Severi S. Theoretical investigation of action potential duration dependence on extracellular Ca2+ in human cardiomyocytes. J Mol Cell Cardiol 2009;46:332-42.
Javanainen T, Ishihara S, Gayat E, Charbit B, Jurkko R, Cinotti R, et al.
Prolonged corrected QT interval is associated with short-term and long-term mortality in critically ill patients: Results from the FROG-ICU study. Intensive Care Med 2019;45:746-8.
Behradmanesh S, Nasri H. Association of serum calcium with level of blood pressure in type 2 diabetic patients. J Nephropathol 2013;2:254-7.
Tabesh M, Azadbakht L, Faghihimani E, Tabesh M, Esmaillzadeh A. Effects of calcium-vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: A randomised controlled clinical trial. Diabetologia 2014;57:2038-47.
Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol 2012;109:359-63.
Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: Reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. BMJ 2011;342:d2040.
Lewis JR, Radavelli-Bagatini S, Rejnmark L, Chen JS, Simpson JM, Lappe JM, et al.
The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: A collaborative meta-analysis of randomized controlled trials. J Bone Miner Res 2015;30:165-75.
Chung M, Tang AM, Fu Z, Wang DD, Newberry SJ. Calcium intake and cardiovascular disease risk: An updated systematic review and meta-analysis. Ann Intern Med 2016;165:856-66.
Reid IR, Bolland MJ. Controversies in medicine: The role of calcium and vitamin D supplements in adults. Med J Aust 2019;211:468-73.
Rodríguez AJ, Scott D, Khan B, Hodge A, English DR, Giles GG, et al.
High calcium intake in men not women is associated with all-cause mortality risk: Melbourne Collaborative Cohort Study. Arch Osteoporos 2018;13:101.
Larsson SC, Orsini N, Wolk A. Dietary calcium intake and risk of stroke: A dose-response meta-analysis. Am J Clin Nutr 2013;97:951-7.
Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res 2014;114:379-93.
Kestenbaum B, Katz R, de Boer I, Hoofnagle A, Sarnak MJ, Shlipak MG, et al.
Vitamin D, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol 2011;58:1433-41.
Houillier P, Nicolet-Barousse L, Maruani G, Paillard M. What keeps serum calcium levels stable? Joint Bone Spine 2003;70:407-13.