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Serum Creatine Kinase-MB Isoenzyme Activity among Subjects with Uncomplicated Essential Hypertension: Any Sex Differences

Mathias Abiodun Emokpae
1,* and
Goodluck O. N. A. Nwagbara
Department of Medical Laboratory Science, University of Benin, Benin City 300283, Nigeria
Defence Reference Laboratory, Health institution, Abuja-Nigeria, FCT-Abuja 900211, Nigeria
Author to whom correspondence should be addressed.
Med. Sci. 2017, 5(2), 8;
Submission received: 3 March 2017 / Revised: 5 April 2017 / Accepted: 21 April 2017 / Published: 27 April 2017
(This article belongs to the Section Cardiovascular Disease)


Hypertension (high blood pressure) is a major health challenge and more women than men are affected by the condition. Complications as a result of this condition often lead to disabilities and premature death. The objective of this study was to evaluate creatine kinase-MB (CK-MB) activity in uncomplicated hypertension and to know whether sex differences exist in the activity of the enzyme. Serum creatine kinase-MB isoenzyme activity, troponin I, and lipid profile were evaluated in 140 male and 100 female Nigerians with hypertension. The control group was comprised of 100 (50 males and 50 females) normotensive subjects. Measured parameters were assayed using Selectra Pros chemistry analyzer. The means were compared between males and females using Students’t-test. The mean CK-MB activity of the female hypertensive subjects was significantly higher (p < 0.001) than the males. Similarly, the mean cardiac troponin I (cTnI) of the female hypertensive subjects was significantly higher (p < 0.001) than the males. Conversely, the mean CK-MB activity of the female normotensive subjects was significantly lower (p < 0.001) than the male counterparts. There was no difference in the levels of cTnI between male and female normotensive subjects. Serum CK-MB activity was higher in female than male hypertensive subjects. In the light of these results, cardiac markers should be routinely done in the evaluation of hypertensive subjects and sex-specific consideration may be recognized in the management of these patients.

1. Introduction

Hypertension in Nigeria has emerged as a major health problem with enormous socioeconomic importance. It is the commonest single risk factor for cardiovascular related events and deaths [1], which includes stroke, congestive heart failure, chronic kidney disease, and coronary artery disease [2]. The condition is under-detected and under-treated as a result of ignorance and poverty. Therefore, complications could occur that may lead to chronic disabilities and premature deaths [3]. The prevalence of hypertension among Nigerians was estimated to be 15% which may not be a true representation of the burden of the disease [4]. In most countries of sub-Saharan Africa, the prevalence of hypertension was reported to be higher in males than females [5,6,7,8,9,10], but the reverse is the case in Nigeria where the prevalence is higher among females than males [11]. Studies have shown that hypertension was the strongest as well as an emerging risk factor for heart failure and stroke in sub-Saharan Africa [12]. Unfortunately, little or no attention has been paid to laboratory assessment of hypertensive subjects and most of the required biomarkers of disease severity and progression are not routinely available in most health facilities in Nigeria. Studies of organ damage in subjects with hypertension showed that hypertensive heart disease, nephropathy, retinopathy, stroke, and ischemic heart disease are common even at the first contact in health care facilities [13,14,15,16,17].
Cardiac biomarkers such as creatine kinase-MB (CK-MB) isoenzyme, troponin I, and lipid profile are important in the evaluation of hypertensive subjects. Creatine kinase-MB has a sensitivity and specificity of >90% for the detection of myocardial injury. Creatine kinase (CK) is an enzyme of two subunits M and/or B with three different pairs of subunits combine to give rise to three different isoenzymes CK-MB, CK-BB, and CK-MM. The CK-MB is the heart specific isoenzyme and used to be the reference method for the diagnosis of acute myocardial infarction in most laboratories and increased levels are frequently interpreted as objective evidence of myocardial injury clinically [18]. Due to the greater cardio-specifity of cardiac troponin I (cTnI) and cardiac troponin T (cTnT), compared to CK-MB, troponins are increasingly used as diagnostic markers for cardiac injury or infarction [19,20,21]. We previously reported higher levels of serum uric acid among Nigerians with essential hypertension. A significantly raised serum uric acid was observed among 59% of male and 62% of female hypertensive subjects [22]. Some studies have reported sex differences for CK activity resulting in the establishment of different reference ranges for men and women [23]. Several authors have reported that black people of West African descent have higher tissue and serum CK activity than Caucasians [24]. It was suggested that high CK activity in black population may be responsible for increased risk of hypertension, since the enzyme aids highly energy-demanding processes in the body such as sodium retention, cardiovascular contractility, and modulation of arteries [24,25,26,27]. Consequently, high CK activity especially in resistance arteries may enhance pressure responses and increase blood pressure [24,25]. It was reported that the impact of misclassification of subjects in clinical or epidemiological studies may be challenging and even misleading if sex differences in CK-MB activity are not taken into consideration [25]. Therefore, analysis of sex differences of some biomarkers of cardiovascular risk events may be important in the management of hypertension. This study evaluates CK-MB activity in uncomplicated hypertension and aims to know whether sex differences exist in the activity of the enzyme among Nigerians with uncomplicated hypertension.

2. Patients and Methods

This prospective case controlled study of 240 hypertensive subjects made up of 140 males aged 48.3 ± 1.15 years; confidence interval (CI): 34–62 years and 100 females aged 44.7 ± 1.7 years; CI: 28–61 years. The control subjects were 100 normotensive subjects made up of 50 males aged 41.7 ± 1.7 years; CI: 29–54 years and 50 females aged 40.0 ± 1.40 years; CI: 28–61 years. The mean systolic blood pressure (SBP) of the male hypertensive subjects was 148.02 ± 2.28 mmHg; CI: 121–174 mmHg and for female hypertensive subjects was 152.16 ± 2.33 mmHg; CI: 129–175 mmHg. The mean diastolic blood pressure (DBP) for the males was 95.32 ± 1.70 mmHg; CI: 75–115 mmHg and for females was 96.23 ± 1.12 mmHg; CI: 85–107 mmHg. The study participants were Nigerians with uniform ethnic background. Among the study participants, 40 males and 30 females were either on nefidepine and/or lisinopril anti-hypertensive treatment.

2.1. Ethical Consideration

The study was approved by Ministry of Defense Health Research Ethics Committee, Abuja-Nigeria (code MODHREC APP/045 dated 3 July 2015) and participants gave informed consent before specimens were obtained.

2.2. Inclusion and Exclusion Criteria

Study participants were hypertensive patients above 18 years of agewho were attending clinic at Defense Headquarters Medical Clinic, Mogadishu Cantonment, Asokoro, Abuja. Those subjects below 18 years and/or diagnosed with hypertension, hypothyroidism, and trauma were excluded from this study. In addition, the subjects who were pregnant or lactating and those who recently donated blood or were vaccinated within the last three months were excluded.

2.3. Specimen Collection

Five milliliters of fasting venous blood were collected from the ante-cubital vein. The blood specimens were allowed to clot at room temperature for 30 min and sera were obtained after centrifugation at 1000× g for 10min. The sera were used for the determination of CK-MB, cTnI, triglyceride, total cholesterol, and high density lipoprotein cholesterol using Selectra Pro S chemistry auto-analyzer, Puteaux, France and reagents supplied by ELITech group, Rotterdam, Netherlands. The low-density lipoprotein (LDL) cholesterol was calculated using Friedewald’s formula [26]. Serum CK-MB activity was measured serially with a minimum of two values on consecutive days for each subject.

2.4. Statistical Analysis

The observed data were normally distributed as tested using W/S test for normal distribution and were analyzed using SPSS version 16 (SPSS Inc., Chicago, IL, USA). Student’s t-test was used to compare the means of the male and female participants and level of significance was set at p ≤ 0.05. Multivariate regression model was used to test the relationship between CK-MB activity, blood pressure, and sex. Subjects with controlled hypertension (SBP < 140 mmHg and DBP < 90 mmHg who were on antihypertensive drugs treatment) were excluded from analysis of the association between CK-MB, blood pressure and sex.

3. Results

As shown in Table 1, the CK-MB activity of the female hypertensive subjects was significantly higher (p < 0.001) than the males. Similarly, the mean cTnI of the female hypertensive subjects was significantly higher (p < 0.001) than the males. Conversely, the mean CK-MB activity of the female normotensive subjects was significantly lower (p < 0.001) than the male counterparts. There was no difference in the levels of cTnI between male and female normotensive subjects. The CK-MB activity was significantly higher in hypertensive than normotensive subjects (Table 2). The multivariate regression analysis of the association between CK-MB activity and SBP (β = 0.19; p = 0.02) and DBP (β = 0.16; p = 0.01) in women and SBP (β = 0.16; p = 0.05) and DBP (β = 0.011; p = 0.08) in men was significant. After excluding women (n = 30) and men (n = 40) on antihypertensive medication, the positive association between CK-MB activity and SBP (β = 18; p = 0.03) and DBP (β = 0.17; p = 0.04) in women remained significant while a non-significant association of SBP (p = 0.09) and DBP (p = 0.10) was observed for the males.

4. Discussion

The main findings in this study are that CK-MB activity and cTnI levels were significantly higher (p < 0.001) in subjects with uncomplicated hypertension than normotensive control subjects. The activity of CK-MB was significantly higher (p < 0.001) in female hypertensive than male hypertensive subjects. On the contrary, the activity of CK-MB in female normotensive control subjects was lower (p < 0.001) than the male controls. In other words, the sex difference observed in the control subjects was reversed in hypertensive individuals.
We did not measure total CK and CK-MB mass in this study, which may constitute a limitation in our study. Some authors have reported that measurement of CK-MB using mass may be better than measuring CK-MB activity [27]. Indeed, the guidelines for the redefinition of acute myocardial infarction recommended the use of CK-MB mass rather than CK-MB activity [28]. It was stated that the problems associated with measuring activity include deactivation of the enzyme activity by experimental manipulations leading to underestimation, especially in the low range of activity. In hemolyzed blood samples, adenylate kinase released from the red blood cells and catalyzed the same reaction as CK-MB which could result in false positive results. The presence of CK-BB, macro creatine kinase type 1 or macro creatine kinase type 2 in high concentrations could interfere with the result and lead to false elevation of CK-MB when activity is measured [18]. The fact that CK activity was not assayed after rest may be a limitation, although exercise mainly increases CK-MM activity.
Sex differences in the levels of measured biomarkers may potentially impact negatively on prognosis and clinical outcome of hypertensive women. Therefore, sex should be considered in the management of hypertension among Nigerians. It was previously reported that the incidence of stroke and atherosclerosis was higher in males than females and that women appear protected from cardiovascular diseases until their mid-80s when their incidence of stroke surpasses that of the men [29]. This suggests that there may be sex-specific factors that protect the females from developing hypertensive complications despite higher levels of the measured biomarkers.
Other studies have reported worse prognosis and clinical outcome in women with respect to cardiovascular complications [30,31,32,33,34,35]. The significantly higher CK-MB activity reported in women than men may have been one of the factors responsible for clinical presentation and prognosis of hypertensive women with various cardiovascular complications. Further evaluation is suggested in order to know whether hypertensive Nigerian women develop cardiovascular complications earlier than men. It was reported that women with acute coronary syndrome tend to have worse long-term and short-term than men [30,31,32,33,34,35]. The reason for the sex differences in prognosis was not clear. Whether it was due to different baseline characteristics or due to physiologic distinction between males and females is yet to be ascertained [36]. Meta-analysis of about 35 studies involving 18,555 women and 49,981 men with ST-segment elevation myocardial infarction showed that women have nearly twice the risk for in-hospital all-cause mortality and 1.5 times the risk for one year all-cause mortality compared with men [37].
Sex differences in CK-MB mass were previously studied only in apparently healthy subjects [25,38] and others evaluated the enzyme activity in hypertensive patients [39,40], acute coronary syndrome, and myocardial infarction [41,42,43]. Strunz et al. (2011) reported that females had significantly lower level of CK-MB mass than males among apparently healthy subjects [38]. The differences were attributed probably to the consequence of a greater body muscle mass in men which may indicate the importance of different decision-limit values based on sex in clinical setting. The authors therefore suggested different cut-off values for both males and females [38]. In a study of distribution of CK activity in order to determine eligible subjects for statin therapy, it was stated that about 49% of black respondents had serum CK activity above the upper limit of the reference range. The authors suggested upward review of the upper limit of reference range for use in clinical settings [44]. No study has reported on sex differences in CK-MB activity among hypertensive Nigerian subjects. However, sex differences in total creatine kinase activity have been observed among hospitalized patients with myocardial infarction [45], psychiatric patients [46], and acute coronary syndrome [33]. Several other authors also reported higher levels of total CK in males than females of the same race [47,48,49,50,51,52,53,54,55]. However, no significant different in the means of total CK activity between males and females was reported among Africans which became significant when mean log total CK was compared [54]. Sex differences in CK activity have been reported in the general population and slight elevations associated with increased risk for myocardial infarction especially in individuals with dyslipidemia [55,56].
The higher CK-MB activity in hypertension is consistent with previous reports [41,57]. It was reported that the enzyme activity was elevated in hypertensive subjects with myocardial infarction [57]. The CK-MB activities have been identified as specific and sensitive biomarker of both clinical and subclinical myocardial injury [58], since they are lightly bound to the contractive apparatus and their level in plasma depends on the severity of myocardial injury. The entry of the enzyme in the circulation depends on the rate of passive diffusion of the enzyme from infarct myocardium cells [41,59]. The exact mechanism of minor CK-MB elevation in subjects with hypertension is not completely clear, but most authors believed the leakage of CK-MB may be due to myocardial injury even though controversy does exist [60,61,62]. It was stated that whether associated with pathologically demonstrable myocardial injury or not, mild elevation of CK-MB is prognostically important [41]. Several studies in patients with suspected infarction have shown that even mildly elevated CK-MB activities are associated with worse clinical outcomes [63,64,65,66,67]. However, long-term mortality in those patients was observed to be similar to patients without CK-MB elevation in another study [68]. In studies involving patients with coronary intervention, CK-MB activity was elevated in 10–40% of the patients and was associated with an increased risk of adverse outcomes [69,70,71,72,73,74,75,76,77]. The multivariate regression analysis of CK-MB activity was significantly associated with blood pressure in females after excluding those subjects on antihypertensive medications. It was previously reported that a long-term usage of Captopril (angiotensin converting enzyme inhibitor) may cause cardiovascular disease [78]. A study that evaluated the levels of CK-MB activity in subjects on angiotensin converting enzyme inhibitor and calcium channel blocker observed that CK-MB activity levels correlated positively with duration of drug use. No significant increase was observed in those that had used the drugs for 1–5 years, but in those that had used the drug for 6–12 years, a significantly higher CK-MB activity was observed [40].
In a study that linked blood pressure with high CK activity, it was observed that blood pressure levels increased with each log of CK activity tertile for blood pressure after adjusting for age, sex, body mass index, and ethnicity [79,80]. There was no evidence that CK clearance was changed in those patients with higher blood pressure levels or that circulating CK was derived from the luminal surface of vascular endothelial cells. It was however stated that higher blood pressure levels may have caused cardiovascular muscle damage and increased total CK activity [79]. They did not assay CK isoenzymes but reported that in subjects with uncomplicated hypertension, a normal CK isoenzyme spectrum coupled with relatively high serum total CK activity was observed [80,81]. These authors offered a possible explanation for the relationship between blood pressure and high serum total CK activity at rest which could be due to tissue activity and absence of overt tissue damage or dysfunction.
Studies have suggested that minor elevations in CK-MB are linked with myocardial necrosis [81,82]. Histological data confirmed that elevated CK-MB without an abnormal increase in total CK activity could be linked to several small areas of myocardial necrosis that associated chronologically with the appearance of CK-MB [83]. It was concluded that myocardial necrosis could result from embolization of plaque microparticles, debris of intravascular friable materials, clots, or cholesterol crystals. Others are transient vessel closure, side branch compromise, and coronary dissection. Embolism could also cause small areas of necrosis because of sudden mismatch between metabolic requirement of myocardium and coronary blood flow [43]. High activity of CK-MB might represent a marker of a high-risk population (such as hypertension) with other risk factors that can adversely affect long-term prognosis [84,85].
Mels et al. (2016) observed absence of any link between CK activity and cardiovascular indices in black men and women despite higher CK activities in black women and worse cardiovascular profile of black population compared with Caucasians [23].

5. Conclusions

In conclusion, serum CK-MB activity was higher in female than male hypertensive subjects. Sex-specific consideration may be considered in the management of these patients.


We appreciate the contributions of all clinical, nursing and Laboratory staff of Defense Headquarters, Abuja, Nigeria.

Authors Contributions

Mathias Abiodun Emokpae conceived and designed the experiments, performed statistical analysis, and wrote the manuscript; Goodluck O.N.A. Nwagbara performed the experiments, collected data, performed statistical analysis, and reviewed the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Lim, S.S.; Vos, T.; Flaxman, A.D.; Danaei, G.; Shibuya, K.; Adair-Rohani, H.; Amann, M.; Anderson, H.R.; Andrews, K.G.; Aryee, M.; et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380, 2224–2260. [Google Scholar] [CrossRef]
  2. Opie, L.H.; Seedat, Y.K. Hypertension in sub-Saharan African populations. Circulation 2005, 112, 3562–3568. [Google Scholar] [CrossRef] [PubMed]
  3. Seedat, Y.K. Hypertension in developing nations in sub-Saharan Africa. J. Hum. Hypertens. 2000, 14, 739–747. [Google Scholar] [CrossRef] [PubMed]
  4. Akinkugbe, O.O. Non-communicable diseases in Nigeria, the next epidemics: Nigeria preparedness. Third biennial Abayomi Bamidele memorial lecture. Niger. J. Clin. Pract. 2000, 3, 37–42. [Google Scholar]
  5. Danaei, G.; Finucane, M.M.; Lin, J.K.; Singh, G.M.; Paciorek, C.J.; Cowan, M.J.; Farzadfar, F.; Stevens, G.A.; Lim, S.S.; Riley, L.M.; et al. National, regional, and global trends in systolic blood pressure since 1980: Systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5.4 million participants. Lancet 2011, 377, 568–577. [Google Scholar] [CrossRef]
  6. Mensah, G.A. Epidemiology of stroke and high blood pressure in Africa. Heart 2008, 94, 697–705. [Google Scholar] [CrossRef] [PubMed]
  7. United Nations Department of Economic and Social Affairs, Population Division. World Population Prospects: The 2008 Revision Population Database; United Nations Department of Economic and Social Affairs, Population Division: New York, NY, USA, 2006. [Google Scholar]
  8. Oladapo, O.O.; Salako, L.; Sodiq, O.; Shoyinka, K.; Adedapo, K.; Falase, A.O. A prevalence of cardiometabolic risk factors among a rural Yoruba south-western Nigerian population: A population-based survey. Cardiovasc. J. Afr. 2010, 21, 26–31. [Google Scholar] [PubMed]
  9. Jones, E.S.; Owen, E.P.; Davidson, J.S.; van Der Merwe, L.; Rayner, B.L. The R563Q mutation of the epithelial sodium channel beta-subunit is associated with hypertension. Cardiovasc. J. Afr. 2010, 22, 241–244. [Google Scholar] [CrossRef] [PubMed]
  10. Bochud, M.; Elston, R.C.; Maillard, M.; Bovet, P.; Schild, L.; Shamlaye, C.; Burnier, M. Heritability of renal function in hypertensive families of African descent in the Seychelles (Indian Ocean). Kidney Int. 2005, 67, 61–69. [Google Scholar] [CrossRef] [PubMed]
  11. Peer, N.; Steyn, K.; Dennison, C.R.; Levett, N.S.; Nyo, M.T.; Nel, J.H.; Commerford, P.J.; Fourie, J.M.; Hill, M.N. Determinants of target organ damage in black hypertensive patients attending primary health care services in Cape Town: The Hi-Hi study. Am. J. Hypertens. 2008, 21, 896–902. [Google Scholar] [CrossRef] [PubMed]
  12. Ogah, O.S.; Rayner, B.L. Recent advances in hypertension in sub-Sahara Africa in: Cardiology in Africa Review series. Heart Online 2013. [Google Scholar] [CrossRef] [PubMed]
  13. Batubenga, M.M.; Omole, O.B.; Bondo, M.C. Factors associated with blood pressure control among patients attending the outpatients clinic of a South Africa district hospital. Trop. Dr. 2015, 45, 1–5. [Google Scholar]
  14. Ekore, R.I.; Ajayi, I.O.; Arije, A. Case finding for hypertension in young adult patients attending a missionary hospital in Nigeria. Afr. Health Sci. 2009, 9, 193–199. [Google Scholar] [PubMed]
  15. Addo, J.; Smeeth, L.; Leon, D.A. Hypertensive target organ damage in Ghanaian civil servants with hypertension. PLoS ONE 2009, 4, e6672. [Google Scholar] [CrossRef] [PubMed]
  16. Stewart, S.; Libhaber, E.; Carrington, M.; Damasceno, A.; Abbasi, H.; Hansen, C.; Wilkinson, D.; Sliwa, K. The clinical consequences and challenges of hypertension in urban-dwelling black Africans: Insights from the Heart of Soweto Study. Int. J. Cardiol. 2009, 146, 22–27. [Google Scholar] [CrossRef] [PubMed]
  17. Oladapo, O.O.; Salako, L.; Sodiq, L.; Shoyinka, K.; Adedapo, K.; Falase, A.O. Target-organ damage and cardiovascular complications in hypertensive Nigerian Yoruba adults: A cross-sectional study. Cardiovasc. J. Afr. 2012, 23, 379–384. [Google Scholar] [CrossRef] [PubMed]
  18. Al-Hadi, H.A.; Fox, K.A. Cardiac markers in the early diagnosis and management of patients with acute coronary syndrome. SQU Med. J. 2009, 9, 231–246. [Google Scholar]
  19. Aeschbacher, S.; Schoen, T.; Bossard, M.; van der, Lely S.; Glattli, K.; Todd, J.; Estis, J.; Risch, M.; Mueller, C.; Risch, L.; et al. Relationship Between High-Sensitivity Cardiac Troponin I and Blood Pressure Among Young and Healthy Adults. Am. J. Hypertens. 2014, 28, 789–796. [Google Scholar] [CrossRef] [PubMed]
  20. Bjurman, C.; Petzold, M.; Venge, P.; Farbemo, J.; Fu, M.L.; Hammarsten, O. High sensitive cardiac troponin, NT-pro BNp, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease. Clin. Biochem. 2015, 48, 302–307. [Google Scholar] [CrossRef] [PubMed]
  21. Welsch, T.M.; Kukes, G.D.; Sandweiss, L.M. Differences of creatine kinase MB and cardiac troponin I concentrations in normal and diseased human myocardium. Ann. Clin. Lab. Sci. 2002, 32, 44–49. [Google Scholar]
  22. Emokpae, M.A.; Abdu, A. Serum Uric acid levels among Nigerians with Essential Hypertension. Niger. J. Physiol. Sci. 2013, 28, 41–44. [Google Scholar] [PubMed]
  23. Mels, C.M.C.; Zyl, C.V.; Huisman, H.W. Cardiovascular function is not associated with creatine kinase activity in a black African population: The SABPA study. BMC Cardiovasc. Disord. 2016, 16, 134. [Google Scholar] [CrossRef] [PubMed]
  24. Brewster, L.M.; Clark, J.F.; van Montfrans, G.A. Is greater tissue activity of creatine kinase the genetic factor increasing hypertension risk in black people of sub-Saharan African descent? J. Hypertens. 2000, 18, 1537–1544. [Google Scholar] [CrossRef] [PubMed]
  25. Apple, F.S.; Quist, H.E.; Doyle, P.J.; Otto, A.P.; Murakami, M.M. Plasma 99th Percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American College of Cardiology Consensus Recommendations. Clin. Chem. 2003, 49, 1331–1336. [Google Scholar] [CrossRef] [PubMed]
  26. Delanghe, J.R.; De Mol, A.M.; De Buyzere, M.L.; DeScheerder, I.K.; Weime, R.J. Mass concentration andactivity concentration of creatine kinase isoenzyme MB compared in serum after acute myocardialinfarction. Clin. Chem. 1990, 36, 149–153. [Google Scholar] [PubMed]
  27. Alpert, J.S.; Thygesen, K. Myocardial Infarction Redefined—A consensus document of the joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of Myocardial Infarction. Eur. Heart J. 2000, 21, 1502–1513. [Google Scholar]
  28. Friedewald, W.T.; Levy, R.L.; Fredrickson, D.S. Estimation of concentration of low density lipoprotein cholesterol in plasma without use of preparative ultracentrifuge. Clin. Chem. 1972, 10, 499–502. [Google Scholar]
  29. National Institute of Health. Sex Differences and Implications for Translational Neuroscience Research: Workshop Summary. National Academy of Sciences, 2011. Available online: (accessed on 6 February 2017).
  30. Ahmad, M.; Arifi, A.A.; van Onselen, R.; Alkodami, A.A.; Zaibag, M.; Khaldi, A.A.; Najm, H.K. Gender differences in the surgical management and early clinical outcome of coronary artery disease: Single centre experience. J. Saudi Heart Assoc. 2010, 22, 47–53. [Google Scholar] [CrossRef] [PubMed]
  31. Dey, S.; Flather, M.D.; Devlin, G.; Brieger, D.; Gurfinkel, E.P.; Steg, P.G.; Fitzgerald, G.; Jackson, E.A.; Eagle, K.A.; Global Registry of Acute Coronary Events investigators. Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: The Global Registry of Acute Coronary Events. Heart 2009, 95, 20–26. [Google Scholar] [CrossRef] [PubMed]
  32. El-Menyar, A.A.; Al Suwaidi, J. Impact of gender in patients with acute coronary syndrome. Expert Rev. Cardiovasc. Ther. 2009, 7, 411–421. [Google Scholar] [CrossRef] [PubMed]
  33. Vaccarino, V.; Rathore, S.S.; Wenger, N.K.; National Registry of Myocardial Infarction Investigators. Sex and racial differences in the management of acute myocardial infarction, 1994 through 2002. N. Engl. J. Med. 2005, 353, 671–682. [Google Scholar] [CrossRef] [PubMed]
  34. Fox, K.A.; Poole-Wilson, P.A.; Henderson, R.A.; Clayton, T.C.; Chamberlan, D.A.; Shaw, T.R.; Wheatley, D.J.; Pocock, S.J.; Randomized Intervention Trial of unstable Angina Investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: The British Heart Foundation RITA 3 randomized trial. Randomized Intervention Trial of unstable Angina. Lancet 2002, 360, 743–751. [Google Scholar] [PubMed]
  35. Lagerqvist, B.; Safstrom, K.; Stahle, E.; Wallentin, L.; Swahn, E.; FRISC II Study Group Investigators. Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? J. Am. Coll. Cardiol. 2001, 38, 41–48. [Google Scholar] [CrossRef]
  36. Assiri, A.S. Gender differences in Clinical presentation and management of patients with acute coronary syndrome in South West of Saudi Arabia. J. Saudi Heart Assoc. 2011, 23, 135–141. [Google Scholar] [CrossRef] [PubMed]
  37. Pancholy, S.B.; Shantha, G.P.S.; Patel, T.; Cheskin, L. Sex differences in short-term and long-term all-cause mortality among patients with ST-Segment elevation myocardial infarction treated by primary percutaneous intervention. A meta analysis. JAMA Intern. Med. 2014, 174, 1822–1830. [Google Scholar] [CrossRef] [PubMed]
  38. Strunz, C.M.C.; Araki, L.M.; Nogueira, A.A.R.; Mansur, A.P. Gender differences in serum creatine kinase-MB mass levels in healthy Brazilian subjects. Braz. J. Med. Biol. Res. 2011, 44, 236–239. [Google Scholar] [CrossRef] [PubMed]
  39. Johnsen, S.H.; Lilleng, H.; Bekkelund, S.I. Creatine Kinase as Predictor of Blood Pressure and Hypertension. Is It All About Body Mass Index? A Follow-up Study of 250 Patients. J. Clin. Hypertens. 2014, 16, 820–826. [Google Scholar] [CrossRef] [PubMed]
  40. Amin, E.A.; Hassan, S.A.; Ali, S.T. ACE1 Relation with cardiac enzyme creatine-kinase-MB levels in hypertensive patients. Iraqi J. Comm. Med. 2009, 22, 260–263. [Google Scholar]
  41. Alexander, J.H.; Sparapani, R.A.; Mahaffey, K.W.; Deckers, J.W.; Newby, L.K.; Ohman, E.M.; Corbalán, R.; Chierchia, S.L.; Boland, J.B.; Simoons, M.L.; et al. Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-Segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. JAMA 2000, 283, 347–353. [Google Scholar] [PubMed]
  42. Pettersson, T.; Ohlsson, O.; Tryding, N. Increased CK-MB (mass concentration) in patients without traditional evidence of acute myocardial infarction. A risk indicator of coronary death. Eur. Heart J. 1992, 13, 1387–1392. [Google Scholar] [CrossRef] [PubMed]
  43. White, R.D.; Grande, P.; Califf, L.; Palmeri, S.T.; Califf, R.M.; Wanger, G.S. Diagnostic and prognostic significance of minimally elevated creatine kinase-MB in suspected acute myocardial infarction. Am. J.Cardiol. 1985, 55, 1478–1484. [Google Scholar] [CrossRef]
  44. Brewster, L.M.; Mairuhu, G.; Strurk, A.; van Montfrans, G.A. Distribution of creatine kinase in the general population: Implications for Statin therapy. Am. Heart J. 2007, 154, 655–661. [Google Scholar] [CrossRef] [PubMed]
  45. Pickering, T.G. Muscular hypertension: Is creatine kinase responsible for hypertension in blacks? J. Clin. Hypertens. 2008, 10, 73–76. [Google Scholar] [CrossRef]
  46. Gledhill, R.F.; Van de Merwe, C.A.; Greyling, M.; Van Niekerk, M.M. Race-gender differences in serum creatine kinase activity: A study among South Africans. J. Neurol. Neurosurg. Psychiatry 1988, 51, 301–304. [Google Scholar] [CrossRef] [PubMed]
  47. Meltzer, H.Y. Factors affecting serum creatine phosphokinase levels in the general population: The role of race, activity and age. Clin. Chim. Acta 1971, 33, 165–172. [Google Scholar] [CrossRef]
  48. Van Steirtegham, A.C.; Robertson, E.A.; Zweig, M.H. Distribution of serum concentrations of creatine kinase MM and BB isoenzymes measured by radioimmunoassay. Clin. Chim. Acta 1979, 93, 25–28. [Google Scholar]
  49. Wong, E.T.; Cobb, C.; Umehara, M.; Wolff, G.; Haywood, L.; Greenberg, T.; Shaw, S., Jr. Heterogeneity of serum creatine kinase activity among racial and gender groups of the population. Am. J. Clin. Pathol. 1983, 79, 582–586. [Google Scholar] [CrossRef] [PubMed]
  50. Miller, W.G.; Gruemer, H.D.; Chinchilli, V.M. Upper reference limit for creatine kinase. Clin. Chem. 1985, 31, 158. [Google Scholar]
  51. Black, H.R.; Quallich, H.; Gareleck, C.B. Racial differences in serum creatine kinase levels. Am. J. Med. 1986, 81, 479–487. [Google Scholar] [CrossRef]
  52. Griffiths, P.D. Serum levels of ATP: Creatine phosphotransferase (creatine kinase). The normal range and effect of muscular activity. Clin. Chim. Acta 1966, 13, 413–420. [Google Scholar] [CrossRef]
  53. Norton, J.P.; Clarkson, P.M.; Graves, J.E.; Lichfield, P.; Kirwan, J. Serum creatine kinase activity and body composition in males and females. Hum. Biol. 1985, 57, 591–598. [Google Scholar] [PubMed]
  54. Cook, J.C.; Wong, E.; Haywood, J. Creatine kinase: Race-gender differences in patients hospitalized for suspected myocardial infarction. J. Natl. Med. Assoc. 1990, 82, 249–254. [Google Scholar] [PubMed]
  55. Brewster, L.M.; Mairuhu, G.; Bindraban, N.R.; Koopmans, R.P.; Clark, J.F.; van Montfrans, G.A. Creatine kinase activity is associated with blood pressure. Circulation 2006, 114, 2034–2039. [Google Scholar] [CrossRef] [PubMed]
  56. Mueller, H.S.; Forman, S.A.; Menegus, M.A.; Cohen, L.S.; Knatterud, G.L.; Braunwald, E. Prognostic significance of nonfatal reinfarction during 3-year follow-up (TIMI) phase II clinical trial. J. Am. Coll.Cardiol. 1995, 26, 900–907. [Google Scholar] [CrossRef]
  57. Hudson, M.P.; Granger, C.B.; Pleper, K.S. Reinfarction after thrombolytic therapy: Experience from the GUSTO-I and II trials. J. Am. Coll. Cardiol. 1999, 33, 325A. [Google Scholar]
  58. Boersma, E.; Pieper, K.S.; Steyerberg, E.W.; Wilcox, R.G.; Chang, W.C.; Lee, K.L.; Akkerhuis, K.M.; Harrington, R.A.; Deckers, J.W.; Armstrong, P.W.; et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-Segment elevation: Results from an International Trials of 9461 patients. The PURSUIT Investigators. Circulation 2000, 101, 2557–2567. [Google Scholar] [CrossRef] [PubMed]
  59. Ahmed, S.A.; Williamson, J.R.; Roberts, R.; Clark, R.E.; Sobel, B.E. The association of increased plasma MB-CPK activity and irreversible ischemic myocardial injury in dog. Circulation 1976, 54, 187–193. [Google Scholar] [CrossRef] [PubMed]
  60. Cohen, L.; Morgan, J.; Gustafson, G. Enzyme and isoenzyme analysis in the coronary care unit. In Principles and Practice of Acute Cardiac Care; Gupta, D.S., Ed.; Year Book: Chicago, IL, USA, 1984; pp. 383–403. [Google Scholar]
  61. Bittl, J.A.; Weisfeld, M.L.; Jacobus, W.E. Creatine kinase of heart mitochondria: The progressive loss of enzyme activity during in vivo ischemia and its correlation to depressed myocardial function. J. Biol. Chem. 1985, 260, 208–214. [Google Scholar] [PubMed]
  62. Marmor, A.; Alpan, G.; Keider, S.; Grendaier, E.; Palant, A. The MB isoenzyme of creatine kinase as an indicator of severity of myocardial ischemia. Lancet. 1978, 2, 812–814. [Google Scholar] [CrossRef]
  63. Hong, R.A.; Licht, J.D.; Wei, J.Y.; Heller, G.V.; Blaustein, A.S.; Pastemak, P.C. Elevated CK-MB with normal total creatine kinase in suspected myocardial infarction. Am. Heart J. 1986, 111, 1041–1047. [Google Scholar] [CrossRef]
  64. Yusuf, S.; Collins, R.; Lin, L.; Sterry, H.; Pearson, M.; Sleight, P. Significance of elevated MB isoenzyme with normal creatine kinase in acute myocardial infarction. Am. J. Cardiol. 1987, 59, 245–250. [Google Scholar] [CrossRef]
  65. Clyne, C.A.; Mederiros, J.L.; Marton, K.I. The prognostic significance of immunoradiometric CK-MB assay (IRMA) diagnosis of myocardial infarction in patients with low total creatine kinas and elevated MB-isoenzyme. Am. Heart J. 1989, 118, 901–906. [Google Scholar] [CrossRef]
  66. Savonitto, S.; Granger, C.B.; Ardissono, D. Even minor elevations of creatine kinase predict increased risk of cardiac events in acute coronary syndromes without ST-Segment elevation. J. Am. Coll. Cardiol. 1999, 33, 346A. [Google Scholar]
  67. Jevric-Causevic, A.; Malenica, M.; Dujic, T. Creatine kinase activity in patients with Diabetes Mellitus type 1 and type II. Bosn. Basic Med. Sci. 2006, 6, 5–9. [Google Scholar]
  68. Calliff, R.M.; Abdelmeguid, A.E.; Kuntz, R.E.; Popma, J.J.; Davidson, C.J.; Cohen, E.A.; Kleiman, N.S.; Mahaffey, K.W.; Topol, E.J.; Pepine, C.J.; et al. Myonecrosis after revascularization procedures. J. Am. Coll. Cardiol. 1988, 31, 241–251. [Google Scholar] [CrossRef]
  69. Adgey, A.A.J.; Mathew, T.P.; Harbinson, M.T. Periprocedural creatine kinase-MB elevations: Long-term impact and clinical implications. Clin. Cardiol. 1999, 22, 257–265. [Google Scholar] [CrossRef] [PubMed]
  70. Harrington, R.A.; Lincoff, A.M.; Califf, R.M.; Holmes, D.R., Jr.; Berdan, L.G.; O’Hanesian, M.A.; Keeler, G.P.; Garratt, K.N.; Ohman, E.M.; Mark, D.B.; et al. Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT). J. Am. Coll. Cardiol. 1995, 25, 1693–1699. [Google Scholar] [CrossRef]
  71. Abdelmeguid, A.E.; Topol, E.J.; Whitlow, P.L.; Sapp, S.K.; Ellis, S.G. Significance of mild transient release of creatine kinase MB fraction after percutaneous coronary interventions. Circulation 1996, 94, 1528–1536. [Google Scholar] [CrossRef] [PubMed]
  72. Kong, T.Q.; Dandson, C.J.; Meyers, S.N.; Tauke, J.T.; Parker, M.A.; Bonow, R.O. Prognostic implication of creatine kinase elevation following elective coronary interventions. JAMA 1997, 277, 461–466. [Google Scholar] [CrossRef] [PubMed]
  73. Tardiff, B.E.; Califf, R.M.; Tcheng, J.E.; Lincoff, A.M.; Sigmon, K.N.; Harrington, R.A.; Mahaffey, K.W.; Ohman, E.M.; Teirstein, P.S.; Blankenship, J.C.; et al. Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention. IMPACT-II Investigators. Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II. J. Am. Coll. Cardiol. 1999, 33, 88–96. [Google Scholar] [PubMed]
  74. Simoons, M.L.; van Den Brand, M.; Lincoff, M.; Harrington, R.; van der Wieken, R. Minimal myocardial damage during coronary interventions associated with impaired outcome. Eur. Heart J. 1999, 33, 88–96. [Google Scholar] [CrossRef] [PubMed]
  75. Cutlip, D.E.; Baim, D.S.; Senerchia, C. Clinical consequences of myocardial infarction following balloon angioplasty or directional coronary atherectomy: Acute and one-year results of the Balloon vs Optimal atherectomy Trial(BOAT). J. Am. Coll. Cardiol. 1997, 29, 187A. [Google Scholar]
  76. Stone, G.W.; Mehran, R.; Lansky, A.J.; Dangas, G.; Kornowski, R.; Leon, M.B.; et al. Long-term influence of CPK-MB elevation on mortality after percutaneous intervention: Analysis of 7359 patients. J. Am. Coll. Cardiol. 1999, 33, 80A. [Google Scholar]
  77. Benneth, P.N.; Brown, M.J. Angiotensin Converting Enzyme (ACE) Inhibitors. Clinical Pharmacology Textbook, 9th ed.; Churchill Livingstone: Edinburgh, UK, 2005; pp. 467–469. [Google Scholar]
  78. Edelman, B.; Koch, T.R.; Raab, C. Evaluation of the new Beckman electrophoretic method for CK-MB: Comparison with ion exchange chromatography and investigation of a reference outpatient population. Clin. Biochem. 1981, 14, 39–44. [Google Scholar] [CrossRef]
  79. Brewster, L.M.; van Bree, S.; de Visser, M.; van Montfrans, G.A. Hypertension in patients with idiopathic hyperCKemia. J. Hypertens. 2004, 22, S253. [Google Scholar] [CrossRef]
  80. Horan, L.G.; Flowers, N.C.; Johnson, J.C. Significance of the diagnostic Q wave of myocardial infarction. Circulation 1971, 43, 428–436. [Google Scholar] [CrossRef] [PubMed]
  81. Grande, P.; Christiansen, C.; Pedersen, A.; Christensen, M.S. Optimal diagnosis in myocardial infarction. A cost-effectiveness study. Circulation 1980, 61, 723–728. [Google Scholar] [CrossRef] [PubMed]
  82. Ljungdahl, L.; Gerhardt, W.; Hofvendahl, S. Serum creatine kinase B subunit activity in diagnosis of acute myocardial infarction. Br. Heart J. 1980, 43, 514–522. [Google Scholar] [CrossRef] [PubMed]
  83. Brewster, L.M.; Taherzadeh, Z.; Clark, J.F.; van Bavel, E.; Wolf, H.; van Montfrans, G.A. Contraction in human resistance arteries depends on creatine kinase. J. Hypertens. 2006, 24, S403. [Google Scholar]
  84. Neubauer, S. The failing heart: An engine out of fuel. N. Engl. J. Med. 2007, 356, 1140–1151. [Google Scholar] [CrossRef] [PubMed]
  85. Delanghe, J.R.; De Mol, A.M.; De Buyzere, M.L.; DeScheerder, I.K.; Weime, R.J. Mass concentration and activity concentration of creatine kinase isoenzyme MB compared in serum after acute myocardial infarction. Clin. Chem. 1990, 36, 149–153. [Google Scholar] [PubMed]
Table 1. Comparison of measured parameters in male and female hypertensive and normotensive subjects (mean ± SEM).
Table 1. Comparison of measured parameters in male and female hypertensive and normotensive subjects (mean ± SEM).
Measured ParametersMale hypertensive Subjects (n = 140)Female Hypertensive Subjects (n = 100)p-ValueMale Normotensive Subjects (n = 50)Female Normotensive Subjects (n = 50)p-Value
Age (Years)48.3 ± 1.15 (34–62)44.7 ± 1.7 (28–61)0.0541.7 ± 1.70 (29–54)40.0 ± 1.40 (28–61)0.50
SBP (mmHg)148.02 ± 2.28 (121–174)152.16 ± 2.33 (129–175)0.6121.17 ± 2.10 (106–136)118.25 ± 2.61 (102–136)0.5
DBP(mmHg)95.32 ± 1.70 (75–115)96.23 ± 1.12 (85–107)0.880.50 ± 2.10 (65–90)71.61 ± 2.16 (56–86)0.001
cTnI (ng/mL)0.074 ± 0.001 (0.062–0.086)0.081 ± 0.001 (0.071–0.90)0.0010.001 ± 0.000.001 ± 0.001.0
CK-MB (U/L)48.6 ± 1.71 (28.6–68.2)56.2 ± 1.50 (41–71)0.00115.5 ± 0.20 (14.0–16.9)14.0 ± 0.25 (12.2–15.8)0.001
Total Cholesterol (mmol/L)5.45 ± 0.13 (3.92–6.98)5.83 ± 0.12 (4.61–7.02)0.013.94 ± 0.12 (3.09–4.79)4.10 ± 0.10 (3.42–4.85)0.1
Triglycerides (mmol/L)1.63 ± 0.03 (1.28–1.98)1.30 ± 0.01 (1.20–1.40)0.020.89 ± 0.04 (0.60–1.17)0.87 ± 0.04 (0.60–1.15)0.6
HDL-c (mmol/L)1.16 ± 0.04 (0.70–1.63)1.30 ± 0.04 (0.92–1.70)0.0011.21 ± 0.05 (0.85–1.56)1.36 ± 0.05 (1.00–1.71)0.005
LDL-c (mmol/L)3.38 ± 0.02 (3.14–3.62)3.78 ± 0.12 (2.58–4.98)0.0022.30 ± 0.10 (1.59–3.00)2.40 ± 0.07 (1.90–2.89)0.2
CK-MB = Creatine kinase-MB isoenzyme; cTnI = cardiac troponin I; DBP = diastolic blood pressure; HDL-c = high density lipoprotein cholesterol; LDL-c = low density lipoprotein cholesterol; SBP: systolic blood pressure. Values in parenthesis are confidence intervals.
Table 2. Serum activity of CK-MB and troponin I levels in hypertensive and normotensive subjects.
Table 2. Serum activity of CK-MB and troponin I levels in hypertensive and normotensive subjects.
ParametersHypertensive Subjects (n = 240)Normotensive Subjects (n = 100)p-Values
CK-MB (U/L)51.6 ± 3.0 (45–58)15.0 ± 0.75(13–16)0.001
cTnI(ng/mL)0.077 ± 0.001(0.055–0.099)0.001 ± 0.00(0–0.001)0.001

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Emokpae, M.A.; Nwagbara, G.O.N.A. Serum Creatine Kinase-MB Isoenzyme Activity among Subjects with Uncomplicated Essential Hypertension: Any Sex Differences. Med. Sci. 2017, 5, 8.

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Emokpae MA, Nwagbara GONA. Serum Creatine Kinase-MB Isoenzyme Activity among Subjects with Uncomplicated Essential Hypertension: Any Sex Differences. Medical Sciences. 2017; 5(2):8.

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Emokpae, Mathias Abiodun, and Goodluck O. N. A. Nwagbara. 2017. "Serum Creatine Kinase-MB Isoenzyme Activity among Subjects with Uncomplicated Essential Hypertension: Any Sex Differences" Medical Sciences 5, no. 2: 8.

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