|Year : 2019 | Volume
| Issue : 2 | Page : 59-68
Assessment of ultrasound flow-mediated dilation of brachial artery in regular blood donors in a Nigerian Tertiary Hospital
Ozoemena Sebastine Oboke1, Adekunle Ayokunle Olakunle Adeyomoye2, Alani S Akanmu3, Olubukola Abeni Omidiji2, Olubusayo Abimbola Agbaje4
1 Department of Radiodiagnosis, Federal Teaching Hospital, Abakaliki, Ebonyi, Nigeria
2 Department of Radiation Biology, Radiotherapy, Radiodiagnosis and Radiography, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria
3 Department of Hematology and Blood Transfusion, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria
4 Department of Radiology, Foremost Diagnostic Centre, Surulere, Lagos, Nigeria
|Date of Web Publication||18-Jul-2019|
Dr. Ozoemena Sebastine Oboke
Department of Radiodiagnosis, Federal Teaching Hospital, Abakaliki, Ebonyi
Background: Iron is a pro-oxidant cofactor that may be linked to cardiovascular disease (CVD) progression and reduction of body iron stores have been hypothesized to reduce the risk of CV disease.
Aim: The aim of this study is to assess reduction in CVD risk susceptibility among regular blood donors compared with nondonors using ultrasound brachial artery flow-mediated dilation (BAFMD).
Settings and Design: A prospective comparative study designed to establish the difference between mean flow-mediated dilatation (FMD) in the patients who are regular blood donors compared with nondonors recruited from a Teaching Hospital donor clinic.
Materials and Methods: Data were collected over 7 months from December 2014 to June 2015. 100 eligible regular male blood donors, aged 21–50 years, were selected from a Teaching Hospital blood donor records and their BAFMD assessed. 50 nondonors/ first time donors, of equivalent age group, consecutively were assessed for comparison. Serum markers of iron stores, markers of oxidative stress and other related cardiac risk factors were also assessed in all patients.
Results: BAFMD was significantly greater in regular blood donors when compared with nondonors (13.95% ± 7.02% vs. 8.20% ± 4.19%, P = 0.000). Serum ferritin was significantly decreased in regular blood donors when compared with nondonors (mean value 41.92 ng/ml ± 23.12 ng/ml vs. 61.97 ± 30.19 ng/ml, P = 0.000), but Hb did not differ between the groups. High FMD was significantly associated with high C-high-density lipoprotein and low C-LDL (r = −0.215*, P = 0.032, r = 0.188, P = 0.031, r = 0.193, P = 0.027, r = 0.0279, P = 0.002, r = 0.139, P = 0.084). LDL was decreased in regular blood donors compared with nondonors.
Conclusion: The study provides prognostic information for assessing ultrasound BAFMD as a cardiac risk marker. Regular blood donors have enhanced cardiovascular function with increased flow-mediated dilation, decreased body iron stores, and decreased oxidative stress compared with nondonors.
Keywords: Blood artery flow-mediated dilation, blood donors, brachial artery, cardiovascular diseases, ultrasound
|How to cite this article:|
Oboke OS, Adeyomoye AA, Akanmu AS, Omidiji OA, Agbaje OA. Assessment of ultrasound flow-mediated dilation of brachial artery in regular blood donors in a Nigerian Tertiary Hospital. West Afr J Radiol 2019;26:59-68
|How to cite this URL:|
Oboke OS, Adeyomoye AA, Akanmu AS, Omidiji OA, Agbaje OA. Assessment of ultrasound flow-mediated dilation of brachial artery in regular blood donors in a Nigerian Tertiary Hospital. West Afr J Radiol [serial online] 2019 [cited 2020 Feb 18];26:59-68. Available from: http://www.wajradiology.org/text.asp?2019/26/2/59/262940
| Introduction|| |
Cardiovascular disease (CVD) refers to the category of chronic diseases involving heart and blood vessels. It is responsible for one-third of global deaths, claiming 17.1 million lives per year with over 80% taking place in low- and middle-income countries and 23.6 million deaths estimated by 2030.,, CVD is the leading and increasing contributor to the global disease burden with high socioeconomic cost.,
Africa has witnessed increased urbanization and lifestyles, factors which have, in turn, raised the incidence of CVD., Studies from South Africa have shown that 32.1% of men and 18.9% of women over 30 years had a 20% or higher risk of developing CVD in the next 10 years.,,, Total deaths in Nigeria as of 2005 are 2.01 million of which 11% are due to CVD with an estimated loss of 400 million dollars in national income.
The risk factors for CVD are many and include the classic ones (hypertension, diabetes, hyperlipidemia, smoking, aging, etc.) and those discovered more recently (hyperhomocysteinemia, oxidative stress, infections, iron overload (IO), systemic inflammation, estrogen deficiency, local factors, and genetic predisposition)., Hypertension remains the most threatening risk factor, with prevalence ranging between 15% and 30% in adults. Extrapolations from studies in Nigeria and elsewhere indicate that 5% of deaths could be due to hypertension, although the mortality rate is higher in developing countries than in developed ones.,,
The Iron-Heart hypothesis first put forth by Sullivan in 1981 suggests that increased body iron stores are a risk factor for coronary heart disease and thus that iron depletion through phlebotomy or other means can reduce risk.,
This risk reduction can be assessed by studies involving endothelial cells whose homeostatic and vasodilator function mediated by nitric oxide have become a useful target for the indirect assessment for risk of CVD.
Endothelial dysfunction is a cardinal feature of vascular disease states such as atherosclerosis and is associated with an increased risk of cardiovascular events. At present, endothelial dysfunction in the peripheral vasculature is an independent predictor of future cardiovascular events in patients with either established CVD or with a risk factor for vascular disease development.
There are many techniques for assessing endothelial function; these can be either invasive or noninvasive. For the assessment of preclinical disease, the ideal technique for measuring endothelial function must be noninvasive, reliable, reproducible, cheap, and easy to perform.
Noninvasive methods of measuring endothelial function include ultrasound flow-mediated dilatation (FMD). Ultrasound FMD is the most widely used method for searching both small and large population studies of adults and pediatric patients susceptible to an acute cardiovascular event (defined as “vulnerable patient”).
In the invasive method, vasoactive agents are delivered via intra-arterial infusion, while the response is measured with high-resolution ultrasound or strain gauge plethysmography.
This study aims to assess reduction in the susceptibility of cardiovascular risk among the population of people who donate blood regularly on the bias of those that have never donated blood, using a high-resolution ultrasound whose noninvasiveness, cheapness and availability serve as advantages over other imaging modalities.
| Materials and Methods|| |
A comparative study designed to establish the difference between mean FMD in the patients who are regular blood donors compared with nondonors recruited from a Teaching Hospital donor clinic. This was a bidisciplinary study conducted by the Radiology and Hematology units of a teaching hospital.
Duration of study
Recruitment into the study was carried out for 7 months with all the ultrasound scans done from December 2014 to June 2015.
The study involved 100 regular blood donors and 50 age-matched controls. This figure was derived using the formula for statistically significant results.
Where n = sample size of each group
u = one-sided percentage point of normal distribution corresponding to 100%-power.
The power of this study was 90%, implying that at least 90% of the study population should have 33% increases in FMD.
v = percentage point of the normal distribution corresponding to (two-sided) significance level.
u1 = expected mean (hypothetic mean).
u0 = universal mean.
For sample size determination, we chose 33% increases in the level of FMD observed consistently in the patients as compared with the universal mean (as obtained from literature) as a good prognostic outcome of CVD risk reduction in the study population.
Universal mean (u0) from literature  is 5.89% ± 2.88%.
Thus expected subject mean (u1) is 7.83% ± 3.83%
At 90% power u = 1.28
At significance level of 5% v = 1.96
n = 64.11
This was rounded up to 150 patients to broaden the base of this study, to account for possible attrition and to improve result reliability.
Inclusion criteria for regular blood donors were male adults between 21 and 50 years of age that have voluntarily donated at least twice within the past 2 years and gave informed consent.
Inclusion criteria for the control group were male adults between 21 and 50 years of age who had never donated blood and gave informed consent.
Exclusion criteria for regular blood donors and the control group were all females and male subjects <21 years and >50 years of age, hypertensive subjects, patients with a history of major bleeding events (including trauma and surgery,) within the past 2 years, diabetes mellitus, previous myocardial infarction, cancer or active chronic inflammatory disease, or alcohol and tobacco use within 6 months.
Clinical measurements taken include age and body mass index (BMI) and blood pressure. Two separate blood pressure readings were taken 30 min apart, and the higher value was taken as the blood pressure.
Laboratory studies conducted by the hematologists were on 15 ml of venous blood drawn from each subject. A volume of 5 ml of this was put into sodium ethylene diamine tetra-acetate (EDTA) specimen bottles. This sample was used for the full blood count, including the red blood cell indices and was analyzed within 2 h of collection. The remaining 10 ml of the blood was transferred to new plain screw-capped disposable plastic tubes and allowed to stand at room temperature until clotted and the clot retracted (about 2 h). This was then centrifuged and sera separated and transferred to plain cryotubes using a transfer pipette. The serum was aliquoted and stored at −80°C until analysis was performed. The full blood count was carried out on the EDTA anticoagulated samples using the Sysmex KX-21N hematology analyzer. Analysis of serum iron and lipids were performed using the Roche/Hitachi 902 autoanalyzer manufactured in Japan. Serum ferritin was determined by the enzyme linked immunoassay method (ELISA) from commercial assay kit, FERRITIN ELISA KIT manufactured by Biotech Laboratories, high-density lipoprotein (HDL)-C PLUS 3rd generation kit manufactured by Roche Diagnostics GMBH, Sandhofer Strasse 116, MANNHEIM, LDL-C PLUS 2nd generation kit manufactured by Roche Diagnostics GMBH, SANDHOFER STRASSE 116, MANNHEIM and TG KIT manufactured by Roche Diagnostics GMBH, SANDHOFER STRASSE 116, MANNHEIM were used for HDL, LDL, and triglyceride, respectively, at a University Teaching Hospital laboratory. The Friedewald formula was used to confirm the value of LDL.
Technique of ultrasound examination
All ultrasound examinations were performed by the researchers using a standardized approach to the measurements brachial artery flow-mediated dilation (BAFMD) based on report of the International Brachial Artery Reactivity Task Force described by Corretti et al. The scans were done in the morning with the participants in a fasting state.
The TOSHIBA Nemio XG SSA-580A Diagnostic Ultrasound System manufactured in Japan, March 2010; equipped with vascular software for two-dimensional imaging, color, and spectral Doppler with a 7.5–10 MHz linear array transducer, attached to a high-quality mainframe, was used to acquire the images.
The patients were positioned supine and made to rest for 10 min with regular blood pressure monitoring until stabilization. The study was conducted, in a quiet room at controlled room temperature (23°C). An ultrasound coupling gel was applied along the medial aspect of the arm at an approximate value of 5 cm above the antecubital fossa and the transducer placed therein, the brachial artery was imaged at this level and the longitudinal image acquired.
The brachial artery diameter ( first baseline value, D1) was obtained by measuring the intima-lumen interface at the diastolic phase [Figure 1]a. Hyperemia was provoked with the sphygmomanometer cuff already positioned on the patient's right forearm and inflated up to 50 mmHg above systolic pressure for 5 min and then deflated. Postocclusion value (D2) measured by the intima-lumen interface at the diastolic phase at 60 s was also obtained [Figure 1]b.
|Figure 1: (a) B mode prehyperaemic sonogram of the arm taken 5 cm proximal to the cubital fossa showing the lumen-intima interface diameter measured as D1. (b) B mode posthyperaemic sonogram of the arm taken 5cm proximal to the cubital fossa showing the lumen-intima interface diameter measured as D2|
Click here to view
The brachial artery FMD was thereafter calculated with the formula: BAFMD = (D2 − D1)/D1 × 100), and the results expressed in percentages.
On the Doppler image flow velocity in cm/second was sampled through the brachial artery at an angle of 60° for Doppler spectral display.
Presence of vascular pathologies (peripheral arterial diseases) was checked and further evaluated by measuring the peak systolic velocity and end-diastolic velocity [Figure 2].
Ethical approval for the study was obtained from the Research and Ethics Committee of the Lagos University Teaching Hospital before commencement of recruitment into the study. In addition, written informed consent was obtained from each patient. All patients were assured of the confidentiality of the volunteered information and examination findings.
Statistical data analysis
The collected data was analyzed using Statistical Package for Social Science (SPSS®) for Windows, version 17.0.1; Chicago, IL 2007 and Microsoft Excel for Windows 2010. Data were expressed as the mean ± standard deviation. The comparison of the measurements from each group was determined using analysis of variance and the post hoc Bonferroni test. Linear and multiple regression analyses were performed with FMD as the dependent variable, and the following as independent variables: serum ferritin, C-HDL, C-LDL, baseline diameter and BMI; to determine their correlation and colinearity. Probability values of P < 0.05 were considered statistically significant.
| Results|| |
A total of 150 patients were enrolled in the study. 100 were regular blood donors (study group) whereas 50 were nondonors (control group).
[Table 1] shows the sociodemographic distribution of the patients in the study population. The mean age for the regular blood donors was 34.63 ± 8.21 years and for the nondonors was 35.12 ± 7.58 years. The mean BMI of the regular blood donors (25.29 ± 3.02 kg/m 2) was not significantly different from that of the non-donors (25.41 ± 3.26 kg/m 2). P =0.536. The highest frequency of blood donors was seen in the 31–35 age range making about 24.7% of the entire study population and the lowest in 46–50 age range, about 11.3% of the entire study population.
The laboratory values of the participants are shown in [Table 2]. Serum ferritin (a marker of iron stores) was significantly decreased in regular blood donors when compared with nondonors (41.92 ± 23.12 vs. 61.97 ± 30.19, P = 0.000). This difference in serum ferritin was also consistent in all the age ranges. Despite severely reduced iron stores in the high-frequency donors, hemoglobin (Hb), and hematocrit did not differ in regular donors versus nondonors. Mean corpuscular volume was significantly lower and red cell distribution width was significantly greater in high-frequency blood donors when compared with low-frequency blood donors. Mean corpuscular Hb concentration did not differ between groups.
The mean HDL of the regular blood donors (1.44 ± 0.41) was not significantly different from that of the nondonors (1.48 ± 0.39), P = 0.576 [Table 3]. Low-density lipoprotein (LDL) was however reduced in the regular blood donors when compared with that of the nondonors (2.20 ± 1.13 vs. 2.68 ± 0.86, P = 0.009).
|Table 3: High and low density lipoprotein values in the study population|
Click here to view
Flow-mediated dilation was significantly increased in the regular blood donors when compared with that of the nondonors (13.95% ± 7.02% vs. 8.20% ± 4.19%, P = 0.000). Estimates of differences in flow-mediated dilation between regular blood donors and nondonors were consistent across age ranges [Table 4] with 75th of the regular donors having an FMD >15% [Figure 1]a and [Figure 1]b.
|Table 4: Mean flow mediated dilatation distribution in the study population|
Click here to view
In a multivariate analysis of the study group higher FMD showed inverse weak correlation with ferritin, LDL and BMI (r = −0.215 P = 0.016, P = 0.027 and r = −0.139 P = 0.084), positive weak correlation HDL (r = 0.188 P = 0.031) and baseline diameter (r = 0.279, P = 0.002), whereas in the control group, lower FMD revealed significant positive weak correlation LDL (r = 0.292x, P = 0.020), higher BMI (r = 0.326 P = 0.005) and baseline diameter (r = 0.240, P = 0.047), while the correlation with HDL (r = −0.047, P = 0.374) and lower serum ferritin (−0.196; P = 0.087) were not statistically significant [Table 5].
|Table 5: Correlation of flow mediated dilatation with serum ferritin, high density lipoprotein, low density lipoprotein and body mass index|
Click here to view
[Table 6] depicts the effect of blood donation on regular blood donors. The study group (regular blood donors) was divided into two, based on the number of times they had donated in the last 3 years (2 units/year donations; >3 units/year donations in the last 3 years) The FMD, serum ferritin, and LDL showed significant differences in these two groups (P = 0.024, P = 0.032 and 0.045), respectively. There was no significant difference noted with HDL (P = 0.325).
|Table 6: Effect of frequency of donation on flow mediated dilatation, serum ferritin and lipid profile|
Click here to view
| Discussion|| |
At the beginning of the 20th century, CVD was responsible for 10% of all deaths worldwide; today, that figure has risen to 30%, with 80% occurring in developing countries. CVD, with a mortality toll of 17.5 million, is the leading cause of death globally.,, Voluntary blood donors have been shown to have a reduced risk of having this disease because of the protective effect of decreased iron stores with a resultant increase in their BAFMD thereby improving vascular function.,
Ultrasound has been proven to be the imaging modality of choice because it is noninvasive, cheap, reproducible, nonionizing, and easy to perform. This study is a prospective study which aims to assess the cardiovascular risk in voluntary blood donors and nondonors using BAFMD.,
With advancing age, there is a decline in FMD which is associated with an increased incidence of CVD., This was also seen in this study which revealed a decline in FMD in the 36–40, 41–45 and 46–50 age range. These findings were at variance with studies by Wray et al. and Jensen-Urstad and Johannsson who found a preserved FMD in the older age group. They attributed their findings to lack of normative FMD reference value for comparison;, their studies also included much younger men <20 years and women.
BMI as a traditional cardiovascular risk factor decreases with activities like exercise and blood donation that would result in an increased vascular function. The BMI in the study group was lower when compared with control. This was similar to the outcome of a prototype study by Fernández-Real (BMI nondonors kg/m 2 27.4 ± 3.6 regular donors/27 ± 2.6). Similar findings but significant was noted by Adias et al., (BMI values of 24.4 ± 2.4 kg/m 2 in the first time donors was significantly higher than the 21.7 ± 1.7 kg/m 2 obtained in repeat donors P < 0.001). This was contrary to the findings of Zheng et al. and Ascherio et al. that noted the BMI of the high frequency donors was higher than the low-frequency donors. This might be due to the fact that both the study and control group were donors.
Iron measured as serum ferritin is an essential but potentially harmful nutrient. In men, iron stores, assessed by serum ferritin concentration, rise after adolescence. It contributes to many important physiologic functions in the body; however, it increases biological markers of oxidative stress, cytotoxicity, and lipid peroxidation in biological systems. Various literature have suggested that the catalytic role of iron in lipid peroxidation may account for the formation of atherosclerotic lesions and loss of endothelial wall integrity. More than three decades ago, it was proposed that iron depletion protects against CVD and that this effect may explain the remarkably low incidence of cardiovascular disorders in menstruating women., This study revealed that regular blood donation and increased frequency of >3 U/year (P = 0.032) as a subset with the study group significantly depleted iron stores measured as serum ferritin. These were similar to the outcome of studies by Klipstein-Grobusch et al., Zheng et al., Orimadegun et al., which also reported reduced incidence of CVD among their own study population. Studying iron stores of Nigerian blood donors Adediran et al. and Usanga  also noted a significantly lower ferritin levels in regular blood donors compared with nondonors and healthy controls, respectively; men in the study group had a lower mean serum ferritin (48.57 ± 45.17 ng/mL) than men in the control group (145.49 ± 87.74 ng/mL, P = 0.00) and Linpisarn et al. in which serum ferritin level was significantly lower in those who donated three times per year compared to the first time donors among the Thai population. These were consistent with the findings of Milman and Kirchhoff  Meyers et al., Mackintosh, and Jacob. Contrary to our finding, Akpotuzor et al. concluded that there was no observable difference in biochemical iron parameters between regular donors and healthy controls. This was attributed to regional differences in the iron parameters. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from CVD. Mean HDL levels in the control group were higher (1.48 ± 0.39) than in the study group (1.44 ± 0.41) but not statistically significant. Low HDL levels were also noted in other similar studies by Zheng et al., Fernández-Real et al. and Jadrić et al. This similar observation was also documented among the regular blood donors in the Nigerian population by Adias et al. This low HDL though within normal range might be due to hidden negative lifestyle such as alcohol consumption and cigarette smoking among the study population. However, a similar study in Chennai in the Indian population by Bharadwaj  reported higher HDL level in recent regular donor's reason being that the past donors had some amount of negation due to the harmful effect of smoking at least up to 1 year from the date of blood donation.
Low-density lipoprotein (LDL) as an oxidative stress maker is known to play an important role in the pathogenesis of atherosclerosis, and CVD,, and low level of LDL have also been associated with reduced risk of CVD among the regular blood donors. This study documented a significantly low LDL (P = 0.000) in the study group compared with the control group. Several studies have also reported similar findings in their patients , This was contrary to the outcome of a similar study by Jadrić et al. who reported significantly higher LDL in regular blood donors. This is because his control groups were women in the reproductive age group who had lower LDL levels as a result of significant iron loss during menstruation.
Flow-mediated dilation (FMD) in the brachial artery is a noninvasive biomarker of vascular function that has been previously reported to be related to endothelium-dependent vasomotion in the coronary circulation and to be significantly associated with clinical outcomes in CVD populations., Findings of enhanced vascular function in association with regular blood donation, suggests that regular blood donation is associated with reduced cardiovascular risk, and this was observed in this study. This finding of enhanced FMD in association with regular blood donation in this study group on the bias of the control group (P = 0.000) is consistent with the findings of the similar study of Zheng et al. (P = 0.0003). Patel et al. studied people with diabetes and reported that brachial artery flow-mediated dilation was also greater in high-frequency donors before and during oral glucose tolerance testing. Nishizaka et al. in a related study of hyperaldosterone and vascular reactivity noted that FMD was significantly lower in 36 patients with hyperaldosteronism (1.8% ± 1.3% vs. 3.9% ± 1.9%, P_=0.0001) compared with the 44 patients without hyperaldosteronism. Dalli et al. in a similar study among men with risk factors of CVDs and men with acute myocardial infarction on the bias of healthy men demonstrated a significantly increased FMD in healthy men (5% ± 2.6% and 7.8% ± 3.1%, respectively P < 0.0001). Similarly, The BAFMD was significantly compromised in the group with risk factors as compared with the control group, regardless of sex as seen in the study of Cristiane et al. In retrospective data analysis of 68 patients undergoing coronary angiography by Suessenbacher et al., an absolute improvement in FMD 3% appears to be related to a lower risk of future cardiovascular events, whereas a single FMD measurement was not associated with clinical outcome during a mean follow-up period of up to 4 years. Furthermore in a related work by Chan et al., an impairment of FMD is associated with cardiovascular events following the measurement of FMD in 152 patients with CAD (P = 0.012.) Modena et al. tested the prognostic role of reversible endothelial dysfunction in 400 postmenopausal mild-to-moderate hypertensive women. In 250 (62.5%) patients, FMD had significantly improved to 10% (mean FMD in this group: 13.9% ± 2.6%) after 6 months of treatment, which was associated with fewer events compared to patients with no change in FMD (5.9% vs. 21.3%). The mean FMD value in the group without improvement was 7.1% ± 2.5%. Interestingly, FMD values in both groups are comparable to the values measured in our study population: 13.9% ± 4.3% in regular blood donors (population of improved FMD with less risk of CVDs) and 8.20% ± 2.9% in nondonors (population of increase in the risk of cardiovascular events).
The findings of Modena et al. and our findings suggest that FMD may be used to individualize risk factor management. In variance to the above findings, Fathi et al., did not find an association between FMD and cardiovascular events in a high-risk population. Possible explanations for this discrepancy include differences in the study population and inter-individual variation of FMD. The latter problem might be overcome when serial measurements are performed.
FMD showed a weak inverse correlation with BMI in the study group. This is similar to the work done by Benjamin et al. on a clinical correlate of FMD and Framingham heart study which showed FMD% to be inversely related to BMI. It is also consistent with similar studies by Ziccardi et al. and Perticone et al. associating endothelial dysfunction with obesity. Peña et al., in a similar study found FMD was significantly related to BMI. This was at variance with the study by Nishizaka et al. where no association was observed between FMD and BMI. This would probably be due to the fact the study population was more of people that had nontraditional risk factors like low-density lipoproteins.
Other authors have also researched the possibility that body iron stores may be related to factors associated with CVD. Meroño et al. analyzed the lipid and lipoprotein metabolism and novel markers of CVD in 20 male patients with iron overload, versus 20 sex- and age-matched healthy controls, as well as their relationship with ferritin concentration and insulin resistance. IO was diagnosed based on: transferrin saturation >45%, ferritin concentration >500 μg L − 1 and homozygosity for HFE gene C282Y or H63D mutations, or increased iron liver stores assessed by semi-quantitative grading in liver biopsies. The main findings of this study included the presence of the so-called atherogenic dyslipidemia in most patients with IO, apart from an increased oxidized LDL concentration and higher (cholesteryl ester transfer protein) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activities, in comparison with age- and sex-matched controls. This is similar to results of Berge et al. who evaluated serum ferritin, sex hormones and cardiovascular risk factors in healthy women and found that ferritin significantly correlated inversely with both total cholesterol and LDL.
Blood donation has not been documented to result in the reduction of hemoglobin and packed cell volume (PCV), this would be accounted for by the laboratory standard of not phlebotomizing an anemic subject. The mean Hb and PCV were not significantly different in the control and study group (P = 0.403 and 0.219), respectively, a finding consistent with laboratory criterion of Lagos University Teaching Hospital that excludes anemic patients from the donation. This is similar to the observations of Zheng et al., who found in their study that there was no significant difference in the Hb in the high-frequency blood donors and first-time donors. These were similar to the observation of study by Uche et al., and Szymczyk-Nuzka and Wołowiec et al. who reported a normal Hb and PCV in 151 regular male donors who had given over 10 units of whole blood with the frequency of 4–6 units per year. Flesland et al., also reported no significant difference in the Hb concentration of regular blood donors and first-time donors. This finding is in contrast to the work of Djalali et al., Jeremiah and Koate, and Okpokam et al., who reported a significantly lower Hb and PCV in regular blood donors when compared with healthy controls. This was attributed to poor economic status of these donors as they donate for monetary gains, poor nutrition status as well as no iron supplement after each donation.
| Conclusion|| |
The findings in this study support a potential link between blood donation and reduced cardiovascular risk and further suggest that ultrasound assessment of BAFMD may be a useful ideal technique for measuring endothelial function since it is noninvasive, reliable, reproducible, cheap, and easy to perform.
The results of the current study are only applicable to a relatively healthy cohort of men without co-existing vascular disease; a population of particular interest with respect to improving primary prevention and risk detection. While both serum ferritin and FMD have been promoted as biomarkers that may be predictive of CVDs risk, the current study could not follow-up the patients to know how many of the study population later developed CVD. Sampling once at 60 s might be also be a limitation.
There is no doubt that a test, which detects silent cardiovascular risk, would allow early intervention by lifestyle change, or medication and primary prevention could start as early as childhood. This is a long run could dramatically reduce the looming socioeconomic burden of CVD on the health system and society at large. Ultrasound BAFMD should be done regularly as a cardio risk marker in our population. Regular blood donation should also be incorporated.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
BeLue R, Okoror TA, Iwelunmor J, Taylor KD, Degboe AN, Agyemang C, et al.
An overview of cardiovascular risk factor burden in sub-Saharan African countries: A socio-cultural perspective. Global Health 2009;5:10.
Cristiane MS, Hilton AK, Carlos AB. Brachial artery flow-mediated dilatation and intima-media thickness of carotid and brachial arteries: Evaluation of individuals with and without risk factors for atherosclerosis. Radiol Bras 2010;43:389-439.
Ezeanyika LU, Ugwu CE, Nwanguma BC. Assessment of cardiovascular disease risk factor of an urban Nigeria hypertensive population using a risk score calculator. Pak J Med Sci 2008;24:390-4.
Kadiri S. Tackling cardiovascular disease in Africa. BMJ 2005;331:711-2.
Akinboboye O, Idris O, Akinboboye O, Akinkugbe O. Trends in coronary artery disease and associated risk factors in sub-Saharan Africans. J Hum Hypertens 2003;17:381-7.
Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: Testing and clinical relevance. Circulation 2007;115:1285-95.
Sani MU, Wahab KW, Yusuf BO, Gbadamosi M, Johnson OV, Gbadamosi A, et al.
Modifiable cardiovascular risk factors among apparently healthy adult Nigerian population – A cross sectional study. BMC Res Notes 2010;3:11.
Ejim EC, Okafor CI, Emehel A, Mbah AU, Onyia U, Egwuonwu T, et al.
Prevalence of cardiovascular risk factors in the middle-aged and elderly population of a Nigerian rural community. J Trop Med 2011;2011:308687.
Jadrić R, Hasić S, Kiseljaković E, Corić J, Prnjavorac B, Winterhalter-Jadrić M, et al.
Blood iron stores reduction affects lipoprotein status – A potential benefit of blood donation. Med Glas (Zenica) 2011;8:146-50.
Hu FB. The iron-heart hypothesis: Search for the ironclad evidence. JAMA 2007;297:639-41.
Al-Qaisi M, Kharbanda RK, Mittal TK, Donald AE. Measurement of endothelial function and its clinical utility for cardiovascular risk. Vasc Health Risk Manag 2008;4:647-52.
Zheng H, Cable R, Spencer B, Votto N, Katz SD. Iron stores and vascular function in voluntary blood donors. Arterioscler Thromb Vasc Biol 2005;25:1577-83.
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al.
Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the international brachial artery reactivity task force. J Am Coll Cardiol 2002;39:257-65.
Rudolph TK, Ruempler K, Schwedhelm E, Tan-Andresen J, Riederer U, Böger RH, et al.
Acute effects of various fast-food meals on vascular function and cardiovascular disease risk markers: The Hamburg burger trial. Am J Clin Nutr 2007;86:334-40.
van Jaarsveld H, Pool GF. Beneficial effects of blood donation on high density lipoprotein concentration and the oxidative potential of low density lipoprotein. Atherosclerosis 2002;161:395-402.
Fuster V, Voute J, Hunn M, Smith SC Jr. Low priority of cardiovascular and chronic diseases on the global health agenda: A cause for concern. Circulation 2007;116:1966-70.
Newcomer SC, Leuenberger UA, Hogeman CS, Proctor DN. Heterogeneous vasodilator responses of human limbs: Influence of age and habitual endurance training. Am J Physiol Heart Circ Physiol 2005;289:H308-15.
Wray DW, Uberoi A, Lawrenson L, Richardson RS. Evidence of preserved endothelial function and vascular plasticity with age. Am J Physiol Heart Circ Physiol 2006;290:H1271-7.
Jensen-Urstad K, Johansson J. Gender difference in age-related changes in vascular function. J Intern Med 2001;250:29-36.
Malik J, Melenovsky V, Wichterle D, Haas T, Simek J, Ceska R, et al.
Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial – FAT). Cardiovasc Res 2001;52:290-8.
Fernández-Real JM, López-Bermejo A, Ricart W. Iron stores, blood donation, and insulin sensitivity and secretion. Clin Chem 2005;51:1201-5.
Adias TC, Igwilo AC, Awortu ZJ. Repeat whole blood donation correlates significantly with reductions in BMI and lipid profiles and increased gamma glutamic transferase (GGT) activity among Nigerian blood donors. Open J Blood Dis 2012;2:90-4.
Ascherio A, Rimm EB, Giovannucci E, Willett WC, Stampfer MJ. Blood donations and risk of coronary heart disease in men. Circulation 2001;103:52-7.
Tuomainen TP, Salonen R, Nyyssönen K, Salonen JT. Cohort study of relation between donating blood and risk of myocardial infarction in 2682 men in Eastern Finland. BMJ 1997;314:793-4.
Salonen JT, Tuomainen TP, Salonen R, Lakka TA, Nyyssönen K. Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio ischaemic heart disease risk factor study. Am J Epidemiol 1998;148:445-51.
Klipstein-Grobusch K, Grobbee DE, den Breeijen JH, Boeing H, Hofman A, Witteman JC, et al.
Dietary iron and risk of myocardial infarction in the Rotterdam study. Am J Epidemiol 1999;149:421-8.
Orimadegun BE, Anetor JI, Adedapo DA, Taylor GO, Onuegbu JA, Olisekodiaka JM. Increased serum iron associated with coronary heart disease among Nigerian adults. Pak J Med Sci 2007;23:518-22.
Adediran A, Uche EI, Adeyemo TA, Damulak DO, Akinbami AA, Akanmu AS, et al.
Iron stores in regular blood donors in Lagos, Nigeria. J Blood Med 2013;4:75-80.
Usanga EA. Iron stores of Nigerian blood donors as assessed by serum ferritin concentration. Cent Afr J Med 1990;36:170-3.
Linpisarn S, Thanangkul O, Suwanraj C, Kaewvichit R, Kricka LJ, Whitehead TP, et al.
Iron deficiency in a Northern Thai population: The effects of iron supplements studied by means of plasma ferritin estimations. Ann Clin Biochem 1984;21(Pt 4):268-74.
Milman N, Kirchhoff M. The influence of blood donation on iron stores assessed by serum ferritin and hemoglobin in a population survey of 1359 Danish women. Ann Hematol 1991;63:27-32.
Meyers DG, Jensen KC, Menitove JE. A historical cohort study of the effect of lowering body iron through blood donation on incident cardiac events. Transfusion 2002;42:1135-9.
Mackintosh W, Jacobs P. Response in serum ferritin and haemoglobin to iron therapy in blood donors. Am J Hematol 1988;27:17-9.
Akpotuzor JO, Isong C, Okpokam DC, Etukudo MH. Levels of serum iron, TIBC, transferrin saturation and PCV in blood donors in Calabar cross rivers state, Nigeria. Pak J Nutr 2008;7:500-2.
Bharadwaj RS. A study of lipid profiles among male voluntary blood donors in Chennai city. Indian J Community Med 2005;30:16-23. [Full text]
Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A, et al.
The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol 2003;42:1037-43.
Zheng H, Patel M, Cable R, Young L, Katz SD. Insulin sensitivity, vascular function, and iron stores in voluntary blood donors. Diabetes Care 2007;30:2685-9.
Nishizaka MK, Zaman MA, Green SA, Renfroe KY, Calhoun DA. Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 2004;109:2857-61.
Dalli E, Segarra L, Ruvira J, Esteban E, Cabrera A, Lliso R, et al.
Brachial artery flow-mediated dilation in healthy men, men with risk factors, and men with acute myocardial infarction. Importance of occlusion-cuff position. Rev Esp Cardiol 2002;55:928-35.
Suessenbacher A, Frick M, Alber HF, Barbieri V, Pachinger O, Weidinger F, et al.
Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events. Vasc Med 2006;11:239-44.
Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol 2002;40:505-10.
Fathi R, Haluska B, Isbel N, Short L, Marwick TH. The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol 2004;43:616-23.
Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF Jr., et al.
Clinical correlates and heritability of flow-mediated dilation in the community: The Framingham heart study. Circulation 2004;109:613-9.
Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, et al.
Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 2002;105:804-9.
Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, et al.
Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: Protective effect of Vitamin C. Diabetes 2001;50:159-65.
Peña AS, Wiltshire E, MacKenzie K, Gent R, Piotto L, Hirte C, et al.
Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and nonobese children. J Clin Endocrinol Metab 2006;91:4467-71.
Meroño T, Gómez L, Sorroche P, Boero L, Arbelbide J, Brites F, et al.
High risk of cardiovascular disease in iron overload patients. Eur J Clin Invest 2011;41:479-86.
Berge LN, Bønaa KH, Nordøy A. Serum ferritin, sex hormones, and cardiovascular risk factors in healthy women. Arterioscler Thromb 1994;14:857-61.
Uche E, Adediran A, Damulak O, Adeyemo T, Akinbami A, Akanmu A, et al.
Lipid profile of regular blood donors. J Blood Med 2013;4:39-42.
Szymczyk-Nuzka M, Wołowiec D. Iron stores in regular blood donors. Pol Arch Med Wewn 2003;110:1415-21.
Flesland O, Eskelund AK, Flesland AB, Falch D, Solheim BG, Seghatchian J, et al.
Transferrin receptor in serum. A new tool in the diagnosis and prevention of iron deficiency in blood donors. Transfus Apher Sci 2004;31:11-6.
Djalali M, Neyestani TR, Bateni J, Siassi F. The effect of repeated blood donations on the iron status of Iranian blood donors attending the Iranian blood transfusion organization. Int J Vitam Nutr Res 2006;76:132-7.
Jeremiah ZA, Koate BB. Anaemia, iron deficiency and iron deficiency anaemia among blood donors in Port Harcourt, Nigeria. Blood Transfus 2010;8:113-7.
Okpokam DC, Emeribe AO, Akpotuzor JO. Frequency of blood donation and iron stores of blood donors in Calabar, cross river, Nigeria. Int J Biomed Lab Sci 2012;1:40-3.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]