European Journal of Cardiovascular Medicine

Metabolic syndrome describes a cluster of cardiovascular risk factors which includes abdominal obesity, dyslipidaemia, hypertension, and increased blood sugar levels. Alone or collectively, they increase the likelihood, morbidity and mortality of cardiovascular disease and the burden of non-communicable disease on the healthcare sector. Most countries around the world have a metabolic syndrome prevalence of 20 – 30 % among their adult populations.^[1] This prevalence was 30 % in India.^[2] There were 35 % of adult females with MS in India while there were 26 % of adult males with metabolic syndrome.^[2] India also has one of the highest burdens of cardiovascular disease (CVD) in the world.^[3] The clinical relevance of identifying CVD risk before its emergence could be seen in the prevention of cardiovascular events.^[3] A complex and incomplete understanding exists of the pathogenesis of metabolic syndrome and the components that make it up.^[4] Calcium and magnesium play an important role in each component of metabolic disorders, and altered serum calcium and magnesium may be associated with high triglyceride levels, hypertension, diabetes, obesity and low high density lipoproteins (HDL) levels.^[4] FRS estimates of 10-year CVD risks are positively and independently related to serum calcium level.^[5] There is no data available for comparison of serum magnesium and Framingham risk score in spite of this, there is lack of data to support the same. Not much Indian data is available, so this study seeks to establish the correlation between serum calcium and serum magnesium with Framingham risk score.

 AIMS AND OBJECTIVES

• To study the correlation between serum calcium and magnesium with Framingham risk score as a predictor of cardiovascular outcome.
• To study the correlation between serum calcium and magnesium and conventional cardiovascular risk factors.

This was a hospital based prospective observational study conducted among 288 adult patients who presented with history and characteristic clinical features of metabolic syndrome, to Karnataka Institute of Medical Sciences, KIMS, Hubballi, over a period of two years from November 2019 to December 2021. The study was conducted after obtaining clearance from Institutional Ethics Committee and written informed consent from the study participants.

Inclusion Criteria

1. Patient who signs informed consent for the study.
2. Patients fulfilling at least three or more components of metabolic syndrome according to NCEP.
3. Abdominal obesity: Waist circumference – Men > 90 cm, Women > 80 cm.
4. Hypertriglyceridaemia: ≥ 150 mg/dl.
5. Low HDL-C: < 40 mg/dl in men and < 50 mg/dl in women.
6. High blood pressure (BP): > 130/85 mmHg.
7. High fasting glucose: > 110 mg/dl.

Exclusion Criteria

1. Patients who do not give consent.
2. Patients who are taking statin or other lipid lowering agents
3. Patients with type 1 diabetes mellitus
4. Patients on drugs like loop diuretics, phenytoin, calcium channel blockers, amphotericin, cisplatin
5. Patients with blood transfusion in last 3 months
6. Patients with chronic kidney disease, thyroid and parathyroid

Sample Size of Estimation

The sample size is estimated by population proportion of metabolic syndrome as estimated by Pushpa Sarkar et al. in the study – metabolic syndrome and its components among population of Holalu village, Karnataka. International Journal of medical science and public health, which was 25 %.^[6]

Assuming the same prevalence rate in our region also, with 95 % of confidence interval (standard deviation 1.96) and a confidence interval of 5 %, the sample size is found to be 288.

Where,

Z = 1.96 for 95 % confidence interval

P = Prevalence 0.8

d = 0.06

Statistical Methods

Data was entered into Microsoft Excel sheet and was analysed using Statistical Package for Social Sciences (SPSS) 22 version software. Categorical data was expressed in the form of frequencies and proportions. Chi square test was used as the test of significance for qualitative data. Continuous data was represented as mean and standard deviation.

The blue trend line represents the general trend of correlation between the two variables. The shaded grey area represents the 95 % confidence interval of this trend line. There was a moderate positive correlation between age (years) and corrected calcium (mg/dL), and this correlation was statistically significant (p =< 0.001).

The mean ± SD of corrected calcium (mg/dL) in the patients with diabetes was 9.32 ± 0.50. The mean ± SD of corrected calcium (mg/dL) in non–diabetics was 9.07 ± 0.46). The corrected calcium (mg/dL) in the patients with diabetes ranged from 8.1 - 10.4. The corrected calcium (mg/dL) in non–diabetics ranged from 8.1 - 10.2.

There was a significant difference between the 2 groups in terms of corrected calcium (mg/dL) (p = 0.001).

The mean ± SD of corrected calcium (mg/dL) in the hypertensive patient was 9.34 ± 0.47. The mean ± SD of corrected calcium (mg/dL) in the normotensive group was 8.79 ± 0.46. The corrected calcium (mg/dL) in the hypertensives ranged from 8.1 - 10.4. The corrected calcium (mg/dL) in the normotensives ranged from 8.1 - 9.7.

There was a significant difference between the 2 groups in terms of corrected calcium (mg/dL) (p =< 0.001).

The mean ± SD of corrected calcium (mg/dL) in patients with high cholesterol was 9.40 ± 0.51. The mean ± SD of corrected calcium (mg/dL) in patients with normal cholesterol was 9.16 ± 0.46. The corrected calcium (mg/dL) in patients with high cholesterol ranged from 8.2 - 10.4. The corrected calcium (mg/dL) in patients with high cholesterol ranged from 8.1 - 10.2. There was a significant difference between the 2 groups in terms of corrected calcium (mg/dL) (p =< 0.001).

The blue trend line represents the general trend of correlation between the two variables. The shaded grey area represents the 95 % confidence interval of this trend line.

There was a strong positive correlation between FRS: Total score and corrected calcium (mg/dL), and this correlation was statistically significant (p =< 0.001).

The blue trend line represents the general trend of correlation between the two variables. The shaded grey area represents the 95 % confidence interval of this trend line. There was a moderate negative correlation between age (years) and magnesium (mg/dL), and this correlation was statistically significant (p =< 0.001).

The mean ± SD of magnesium (mg/dL) in the male group was 1.67 ± 0.60. The mean ± SD of magnesium (mg/dL) in the female group was 1.92 ± 0.57. The magnesium (mg/dL) in males ranged from 0.8 - 2.8. The magnesium (mg/dL) in females ranged from 0.8 - 2.7. There was a significant difference between the 2 groups in terms of magnesium (mg/dL) (p = 0.001).

The mean ± SD of magnesium (mg/dL) in diabetes group was 1.69 ± 0.60. The mean ± SD of magnesium (mg/dL) in non–diabetics was 2.20 ± 0.33. The magnesium (mg/dL) in the diabetes group ranged from 0.8 - 2.8. The magnesium (mg/dL) in non–diabetics ranged from 0.9 - 2.7. There was a significant difference between the 2 groups in terms of serum magnesium (mg/dL) (p =< 0.001).

The mean ± SD of magnesium (mg/dL) amongst hypertensives was 1.73 ± 0.60. The mean ± SD of magnesium (mg/dL) amongst normotensives was 2.11 ± 0.46. The magnesium (mg/dL) amongst hypertensives ranged from 0.8 - 2.8. The magnesium (mg/dL) amongst normotensives ranged from 1 - 2.6. There was a significant difference between the 2 groups in terms of magnesium (mg/dL) (p = 0.001),

The mean ± SD of magnesium (mg/dL) in patients with high cholesterol was 1.62 ± 0.61. The mean ± SD of magnesium (mg/dL) in patients with normal cholesterol was 1.94 ± 0.54. The magnesium (mg/dL in patients with high cholesterol ranged from 0.8 - 2.6. The magnesium (mg/dL) in patients with normal cholesterol ranged from 0.8 - 2.8. There was a significant difference between the 2 groups in terms of magnesium (mg/dL) (p =< 0.001).

Individual points represent individual cases. The blue trend line represents the general trend of correlation between the two variables. The shaded grey area represents the 95 % confidence interval of this trend line. There was a strong negative correlation between FRS: Total score and magnesium (mg/dL), and this correlation was statistically significant (rho = -0.88, p =< 0.001).

The mean ± SD of magnesium (mg/dL) in the FRS Risk: Intermediate group was 2.03 ± 0.20. The mean ± SD of magnesium (mg/dL) in the FRS Risk: High group was 1.12 ± 0.27. The magnesium (mg/dL) in the FRS Risk: Low ranged from 1.4 - 2.8. The magnesium (mg/dL) in the FRS Risk: Intermediate ranged from 1 - 2.4. The magnesium (mg/dL) in the FRS Risk: High ranged from 0.8 - 1.9. There was a significant difference between the 3 groups in terms of magnesium (mg/dL (p =< 0.001).

Serum Calcium and Systemic Hypertension among Different Studies

Our study showed a significant correlation between albumin corrected serum calcium and systemic hypertension, with mean corrected calcium being 9.34 ± 0.47 and p = 0.001. In 2011, Sun Hang Park et al.^[7] concluded that serum calcium concentration was significantly and positively correlated with diastolic blood pressure, after adjusting for age and BMI in middle aged men, with p < 0.01. In 2012 Hazari et al.^[8] showed that there was no correlation between serum calcium and systemic hypertension. In 2013, Y Yao et al.^[9] concluded that serum calcium level is associated with increased risk of hypertension in the both male and female, especially among the male population. Also, high serum calcium and albumin corrected calcium were strong predictors of future hypertension. In 2019, Prasanna Kumar et al.^[4] concluded that there was no significant association between serum calcium and systemic hypertension. In 2020, Chou et al.^[10] concluded that higher serum calcium and ACCA are associated with an increased risk of developing hypertension, especially among the males. Serum calcium and ACCA are associated with increased prevalence of hypertension

Serum Calcium and Diabetes Mellitus among Different Studies

Our study showed a significant correlation between albumin corrected serum calcium and diabetes mellitus, with mean corrected calcium being 9.32 ± 0.50 and p value of p = 0.001. In 2011, Sun Hyang Park et al.^[7] concluded that serum calcium concentration was not related to fasting glucose. Their results differed from others probably due to their study having fewer subjects with glucose abnormality than subjects with normal glucose levels. In 2015, C. W. Sing et al.^[11] performed a retrospective cohort study, and concluded that serum total calcium and albumin-corrected calcium were associated with incident diabetes. In 2019, Prasanna Kumar et al. concluded that there was no significant association between serum calcium and systemic diabetes mellitus. In 2020, Cheng-Wai Chou et al.^[10] performed a cross-sectional study concluded that higher serum calcium and ACCA are associated with an increased prevalence and risk of developing diabetes mellitus, especially among the male population.

In evaluation of patients with cardiovascular disease, the evaluation for metabolic syndrome has been an integral part of the clinical work up. However, establishing the diagnosis of metabolic syndrome can be expensive. Serum calcium and serum magnesium are closely linked and associated with metabolic syndrome and its components. Thus, by having a comparison to Framingham risk score, they can be used to assess risk of developing cardiovascular disease (CVD) as simple test. These findings suggest that it may be possible to slow the development and progression of cardiovascular disease in individuals with high or borderline high serum calcium, and low or borderline low serum magnesium level by practicing preventive strategies.

Limitations Of The Study

As there were not enough studies correlating serum calcium and serum magnesium with Framingham risk score, a conclusive deduction cannot be established with the current data and a larger follow up study is needed to evaluate this relationship.

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