Is there an Association between Vitamin D Status and Left Ventricular Ejection Fraction

Background and aim:  Some recent studies have shown that vitamin D deficiency was a common finding in patients with cardiovascular disease. Because of the high prevalence of cardiovascular disease and vitamin D deficiency in Iranian population, we examined the correlation between vitamin D blood levels and patients with heart failure (HF).

Material and Methods: This analytical cross-sectional study was performed using a randomized sampling technique. One hundred forty-five patients who were admitted to hospitals in Tehran from November 2021 to April 2022 participated in this study. Descriptive analysis and inference tests, including chi-square and t-test were used. Logistic regression tests were also used to find the correlations between variables. A P value less than 0.05 was considered for statistical significance.

Results: In aggregate, 145 patients with an average age of 59.91 ± 10.75 years were studied. The average amount of vitamin D was 13.3 ± 12.8 ng/ml. This average was 15.0 ±14.2 ng/ml in patients with normal ejection fraction (EF), 14.6 ± 12.9 ng/ml in patients with mild severity EF, 14.1 ± 11.8 ng/ml and 8.7 ± 5.6 ng/ml in moderate and severe severity EF respectively. (p=0.51)

Discussion: Although, in our studies, low levels of serum vitamin D and diabetes were not significantly associated with EF, but preventing them is essential in mitigating risk factors in HF.

HF is a heart disorder syndrome that is diagnosed by a reduction of left ventricular ejection fraction (LVEF) in combination with water and sodium retention. Muscle weakness and early fatigue are both common manifestations in HF patients [1,2]. The etiology of HF is not well understood [3]. In a recent observational study in patients with severe HF; vitamin D deficiency was a common finding [4] Severe vitamin D deficiency is associated with cardiovascular dysfunction; death due to HF and sudden cardiac attack; which is common in patients referred to angiography [5].

Vitamin D deficiency is a highly prevalent; global phenomenon. Recently; the incidence of vitamin D deficiency seems to be on the rise and is related in part due to reduced sun exposure and increased indoor lifestyles along with efforts to minimize sun exposure. Also; there is evidence proposing that the global increase in obesity is also associated with vitamin D deficiency due to its sequestration in adipose tissue [6].

Iran; in keeping with many Mediterranean countries; has high solar radiation during most days of the year. Results of studies in Iran among different age-groups indicate a high prevalence of vitamin D deficiency [7-10].

Ecological evidence suggests an association between vitamin D status and cardiovascular disease (prevalent and incident heart disease; such as coronary disease and HF; stroke; and risk factors for heart disease such as hypertension and coronary artery calcification) [11,12]. To date; several mechanisms for this link have been offered including endothelial dysfunction; vascular compliance; inflammation; and some effects relating to parathyroid hormone (PTH) renin angiotensin system; and others [13-16].

Because of the high prevalence of coronary disease and low blood level of vitamin D in Iran we decided to measure serum serum 25-hydroxycholecalciferol (25(OH)D) concentrations in all patients that underwent coronary arteries bypass grafts to understand the relationship between the blood level of vitamin D and LVEF.

This was an analytical cross-sectional study approved by our ethics committee. Patients were asked to sign an informed consent form before blood samples were obtained. All the terms of the Helsinki declaration were considered; and the personal information remained anonymous. This registry collected information on patients admitted for CABG surgery in two University hospitals in Tehran between the period of November 2021 to April 2022. Our sample was restricted to participants aged 18 years and above and enrolled patients were limited to those who presented as suitable candidates for CABG surgery.

One hundred forty-five patients agreed to participate in the study to assess their vitamin D status. Complete data for vitamin D serum levels were available from 137 persons; corresponding to 94.5% of the target population whereas for left ventricular ejection fraction; data from 142 patients was collected; corresponding to 97.9% of the target population.

Data Collection Vitamin D

serum 25-hydroxycholecalciferol (25(OH)D) concentrations was evaluated by measuring serum 25-hydroxyvitamin D (25 (OH) D) concentration; as this is the primary circulating form of vitamin D. This serum concentration of 25(OH)D is routinely considered as the robust “gold standard” indicator of vitamin D status [17].

After the patients were admitted; we collected serum samples and examined serum levels of 25 (OH) D in all 145 patients. Serum samples were sent to our central laboratory for analysis. Enzyme-linked Immunosorbent Assay (ELISA) and Immunodiagnostic System Ltd (IDS ltd) Kit; Boldon-UK with 2 nmol/ml sensitivity measurement for 25 (OH) D assays were performed. We classified serum levels of vitamin D into three groups; group 1 is Levels <=15 ng/ml; group 2 is levels 15-30 ng/ml and group 3 is levels >=30 ng/ml [18,19].

Left ventricular ejection fraction (LVEF)

We measured left ventricular ejection fraction (LVEF) in all 145 patients by echocardiography using an Epic 7c Philips ultrasound (Manufactured by Philips Ultrasound 22100 Bothell-Everett Highway; Bothell; WA 98021-8431 USA) and classified the measurements into four groups: normal LVEFs are >55%; mild LVEFs are 45-55%; moderate LVEFs are 35-44% and severe LVEFs are <35 href="#_ENREF_20">20,21].

Statistical analyses

Data were analyzed using statistical package for social sciences (SPSS) version 16 (SPSS Inc. Chicago; IL) for windows. Normal distribution variables (approved by one-sample Kolmogorov–Smirnov test) were compared using independent sample t-test between the groups and paired sample t-test within the groups. Chi square test also was used to compare categorical variables in the two groups. P value lessthen 0.05 was considered statistically significant.

In total; 145 patients with an average age of 59.91 ± 10.75 years were studied. 126 patients (86.9%) were men; and 19 patients (13.1%) were women. A meaningful difference in demographic information among patients with normal; mild; moderate; and severe EF was not observed.

Thirty-eight patients (26.8%) had diabetes. (Table1). There was no significant between the groups. (p=0.176)

Fifty-three patients (37.3%) were with hypertension with no significant difference. (p=0.038) (Table1)

Forty-two patients (29.6%) had hyperlipidemia. No significant difference was seen. (Table1) (p=0.121)

There was no significant difference between groups in average hospitalization; average time of CPB (or CABG surgery); average time of cross clamp; average amount of calcium; phosphate; parathyroid hormone and vitamin D. (Table 1) The Average hospitalization was 6.24 ± 1.63 days. (p=0.35); The average time of CPB (or CABG surgery) was 60.9 ± 19.2 minutes. (p=0.107); The average time of cross clamp was 37.6 ± 15.9 minutes. (p=0.351); The average amount of calcium in the blood of patients was 9.15 ± 0.52 mmol/l. (p=0.23); The average amount of phosphate in the blood of patients was 3.85 ± 0.63 mmol/l. (p=0.36); The average amount of parathyroid hormone (PTH) measured in the serum of patients was 78.82 ± 38.25 pg/ml. (p=0.22); The average amount of vitamin D in the blood of patients was 13.31 ± 12.8 ng/ml. (p=0.51).

Table 1: Demographic Data of Patients

The highest incidence of heart failure worldwide; is reported in Asian countries [22-24]. One of the most important HF indicators is LVEF which is divided to reduced or preserved. Hypertension and age are considered as important risk factors in both forms of reduced and preserved EF. In this study; many factors regarding the impact on EF are considered; for which we provide a brief analysis of the most important ones.

Blood pressure and heart failure with ejection fraction

According to World Health Organization data; patients with hypertension are 40% more predisposed to heart failure [25]; while aging plays a direct correlation in increasing the risk of HF in hypertensive patients. Coronary Artery Disease (CAD); Diabetes; Left Ventricular Hypertrophy (LVH); and valvular diseases also increase the risk of developing HF [26].  In our study we found that high blood pressure affects EF significantly. This finding in the Iranian population is in concordance with other studies conducted in European populations and in the US as well [27,28]. Also; the study conducted by Rajer et.al. in Poland [29] found the same results in considering the impact of hypertension on HF diagnosed with Heart Failure with preserved EF (HF-PEF) and based on European Society of Cardiology guidelines (ESC) 2012 [30].

Diabetes and heart failure with ejection fraction

Even though diabetes was known to be one of the risk factors of Heart Failure with Reduced EF (HF-REF) in studies conducted by Kristensen et.al; [31] we did not find a significant correlation between diabetes and HF. Of course; this difference can be due to the fact that there was no separation between two forms of preserved and reduced EF in our study.

Although diabetes is proven as an important risk factor for atherosclerosis; it is less recognized regarding HF [32]. Framingham et.al have showed that the incidence of heart failure in men and women with diabetes also confirmed this statement [33]. While there are studies that show almost 30%-50% of patients who have HF-PEF; suffer from diabetes as well [34].

Vitamin D and heart failure with ejection fraction

We investigated the relationship between serum serum 25-hydroxycholecalciferol (25(OH)D) concentrations and EF. Our results showed no significant relation. 

Since vitamin D plays a role in the expression of nearly 3000 genes; its deficiency can potentially affect development of various diseases [35]. In many studies; including those conducted by Michaelsson et al. [36]; Joergensen et al. [37]; Pilz et al. [38]; and James et al. [39]; lack of vitamin D lead to HF.

Vitamin D deficiency seems to be a global phenomenon. Even in studies conducted in tropical countries such as Singapore [40]. and Saudi Arabia [41]. this deficiency does exist. BIX studies conducted in Singapore showed that vitamin D deficiency may be due to dyslipidemia and consequently Cardiovascular diseases (CVD) [40]. These results indicate that Vitamin D deficiency is considered as one of the potential risk factors for cardiovascular diseases; including insulin resistance; AD; hypertension and glucose intolerance.

The level of serum PTH and heart failure

We have also investigated the relationship between the factors including calcium and phosphate; bypass time (CPB); clamp time; and lipid profile with EF. No significant relation was observed. These factors may play a role in HF through interactions with each other. It is even possible that they are only involved in HF-PEF which was not investigated in our study.

Studies showed a high level of Parathyroid Hormone (PTH) in HF [42]. However; PTH investigation without measuring 25(OH)-vitamin D may be of value since they are related to each other. Evidence indicates that they have an important role in Cardiovascular diseases [43]. However; our study could not show a significant correlation between Vitamin D and EF but PTH and EF were related as expected.

we could not show any significant relationship between Vitamin D and EF; which is one of the most important indicators of HF; while hypertension was significantly related to EF. Further studies may be required due to the fact that we did not separate two types of reduced and preserved EF in our study.

Acknowledgements: None

Funding details: No funding to declare. 

Authors’ Contributions: All authors contributed equally to this study.

The authors report no conflicts of interest/ No potential conflicts of interest relevant to this article were reported.