Keywords |
| QT interval, Electrocardiogram, Anemia, Anisocytosis, Macrocytosis |
Introduction |
| A high risk of sudden cardiac death was previously demonstrated in hypertensive patients,
related to left ventricular hypertrophy, myocardial ischemia, interstitial fibrosis and autonomic
imbalances.1 |
| Anemia, a global public health problem, affecting both developing and developed countries, is
known as a negative prognosis factor in cardiovascular diseases and a strong predictor of death. |
| Electrocardiographic changes were previously mentioned in patients with chronic anemia.2,3 |
| Prolonged ECG QT intervals are predictors of sudden cardiac death.4,5 |
Aim |
| The aim of the present study was to assess the relationship between anemia and QT intervals in
hypertensive patients. |
Material and Method |
| A total of 72 consecutive hypertensive patients were enrolled in the study. They underwent
standard 12-lead ECG and complete blood count was performed. The investigations conformed
to the principles outlined in the Declaration of Helsinki6 and were approved by the Ethics
Committee of the university. |
Inclusion criteria |
| Consecutive patients diagnosed with hypertension according to the criteria of the European
Society of Hypertension7 were included. A written informed consent of the patients was
requested. |
Exclusion criteria |
| The most important exclusion criteria were: atrial flutter, atrial fibrillation, electrolytic
imbalances, systemic inflammatory processes, active infections and trauma, peripheral edema,
chronic obstructive pulmonary disease, history of myocardial infarction, therapy with
angiotensin converting enzyme inhibitors and angiotensin receptor blockers. |
Sample size and power of the study |
| A power analysis was conducted to determine the number of participants needed in the present
study. The minimum sample size required for regression analysis was 54 (anticipated effect size:
0.15; desired statistical power level: 0.8). |
Standard 12-lead ECG |
| The participants underwent standard 12-lead ECG at a paper speed of 25 mm/seconds. The QT
interval duration was manually measured, from the beginning of the Q wave (or R wave) to the end of the T wave, in all measurable leads. Maximal QT interval duration in all measurable leads
(QTmax), heart rate corrected QT interval according to Bazett formula (QTc), QT interval in
lead DII (QTII), heart rate corrected QTII interval (QTIIc) and QT dispersion (QTd) were
assessed. QTd was calculated as the difference between the maximal and minimal duration of the
QT interval in all measurable leads. Two consecutive QT intervals were measured for each ECG
and the arithmetic mean was calculated. A QT interval of 450 ms was considered prolonged. |
Complete blood count |
| Complete blood count was also performed: red blood cell count (RBC), hemoglobin (Hb),
hematocrite (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH),
mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW).
Anemia was defined using the World Health Organization criteria: hemoglobin levels < 12 g/dL
in women and < 13 g/dL in men, macrocytosis as MCV>97 fl and anisocytosis as RDW>15%. |
Statistical methods |
| Categorical data are given as numbers and percentages, continuous data are given as
means±standard deviation (SD). Sensitivity and specificity, linear and multiple regression
analysis were used as statistical methods. |
Results |
| The study population comprised 72 hypertensive patients, aged 63±12 years, 39% male. The data
obtained for QT intervals and complete blood count results are included in table 1. |
Regression analysis |
| Linear regression analysis revealed significant associations between prolonged QTc and
increased QTd and anemia and macrocytosis, respectively (table 2). |
| Multiple regression analysis revealed a significant association between RDW>15% and
prolonged QTc and QTIIc (table 3). |
Sensitivity and specificity |
| The most sensitive and specific predictor of prolonged QTc and QTIIc was anisocytosis. Anemia
was the most sensitive predictor of QTd > 60ms and macrocytosis, the most specific (table 4). |
Discussion |
| The most important finding of the present paper is the association between prolonged QT
intervals and anemia, macrocytosis and anisocytosis, respectively. |
| Increased red cell distribution width (RDW) was associated with a worse outcome in several
cardiovascular diseases7-10 and with mortality in the general population.11 The correlation
between RDW, a measurement of the variability in size of circulating erythrocytes, and
inflammatory markers, biomarkers of ineffective erythropoiesis, undernutrition and impaired
renal function explained the association between RDW and adverse outcomes in heart failure
patients[8] Increased RDW was associated with a worse outcome in myocardial infarction
patients too, with or without anemia.9 |
| Hemoglobin concentration was previously found as a predictor of prolonged QT intervals in
chronic kidney disease patients.12 |
| A shortened QT interval was observed in patients with iron deficiency anemia, and a positive
correlation was found between serum ferritin and QTc. |
| Scheller et al.3 reported a gradual prolongation of the QT and QTc interval in normovolemic
anemia. |
| Anemia may increase cardiac output and heart rate, may lead to eccentric left ventricular
hypertrophy, activation of the sympathetic nervous system, stimulation of the renin angiotensin
aldosterone system, and is closely associated with chronic inflammation and increased oxidative
stress.14 Tissue hypoxia and changes in blood flow patterns due to low hemoglobin may play an
atherogenic role.14 The pathophysiological link between anemia and prolonged QT intervals is,
probably, hypoxia and decreased myocardial oxygen supply. Anisocytosis appears as an early
sign of anemia, also linked with prolonged QT intervals. The results of the present study indicate
that macrocytosis and the degree of heterogenous distribution of red blood cells provide
important additive prognostic information. Thus, the present paper reports, for the first time, as
far as we know, an association between QT intervals and macrocytosis and anisocytosis,
respectively. |
| The most important limitations of the present study are due to the use of the Bazett formula for
heart rate adjustment of QT intervals, methodological differences in delineating the end of the T
interval, several sources of variability of the QT interval and lack of standardization of QT
dispersion data. |
| The Bazett formula results in overcorrection of the QT interval at higher heart rates and
undercorrection at lower heart rates.15 Despite the mentioned limitation, it is the most frequently
used in clinical practice and it is appropriate for the average physiological heart rate. The heart
rates of the patients in the present study ranged between 52 and 113 beats/minute. Only 6
patients had a heart rate below 60 beats/minute and only 2 >100 beats/minute. |
| Methodological differences in delineating the end of the T interval may appear if the T wave is
flat or bizarre.16,17 Leads, in which the Tend could not be assessed, were eliminated in the present
study. |
| Comorbidities, including age, diabetes mellitus (25% of the patients included in the study
population), obesity (28%), dyslipidemia (14%), smoking (35%), left ventricular hypertrophy
(63%), renal failure (3%), and therapy, including beta-blockers (74%), may change QT interval
duration.15-20 However, the number of comorbidities was low in the present study, considering
that mainly newly diagnosed hypertensive patients were included. Electrolytic imbalances,
systemic inflammatory processes, active infections, chronic obstructive pulmonary disease and
history of myocardial infarction were exclusion criteria. Patients taking angiotensin converting
enzyme inhibitors and angiotensin receptor blockers, known to suppress erythropoiesis21 have
been also excluded. |
Conclusion |
| Anemia, macrocytosis and anisocytosis predict prolonged QT intervals in hypertensive patients
and may contribute to risk assessment of sudden cardiac death. Longitudinal studies are needed
to confirm the association between complete blood count and ventricular arrhythmias and sudden
cardiac death. The advantage to treat anemia in hypertensive patients for reducing the risk of
sudden cardiac death due to ventricular arrhythmias remains to be demonstrated. |
Conflict of Interest: |
| None declared. |
References |
- Breijo-Marquez FR. Cardiac arrhythmias. New Considerations. Rijeka, Croatia: InTech.2012:236.
- Stanojevic M, Stankov S: Electrocardiographic changes in patients with chronic anemia. SrpArhCelokLek. 1998;126(11-12):461-6.
- Scheller B, Pipa G, Kertscho H, et al: Low haemoglobin levels during normovolemia areassociated with electrocardiographic changes in pigs. Shock.2011;34(4):375-81.
- Al-Khatib SM, Allen La Pointe NM, Kramer JM et al: What clinicians should know aboutthe QT interval.JAMA.2003; 289(16):2120-2127.
- Rautaharju PM, Surawicz B, Gettes LS: AHA/ACCF/HRS Recommendations for theStandardization and Interpretation of the Electrocardiogram: Part IV: The ST Segment, Tand U Waves, and the QT Interval A Scientific Statement From the American HeartAssociation Electrocardiography and Arrhythmias Committee, Council on ClinicalCardiology; the American College of Cardiology Foundation; and the Heart Rhythm SocietyEndorsed by the International Society for Computerized Electrocardiology. J Am CollCardiol. 2009; 53:982-991.
- World Medical Association Declaration of Helsinki Recommendations guiding physicians inbiomedical research involving human subjects. Cardiovascular Research 1997;35(1):2-3.
- Mancia G, De Baker G, Dominiczak A, et al: Guidelines for the management of arterialhypertension. Eur Heart J. 2007;28:1462-536.
- Forhecz Z, Gombos T, Borgulya G, et al: Red cell distribution width in heart failure:prediction of clinical events and relationship with markers of ineffective erythropoiesis,inflammation, renal function, and nutritional state. Am Heart J. 2009;158(4):659-66.
- Dabbah S, Hammerman H, Markiewicz W, et al: Relation between red cell distributionwidth and clinical outcomes after acute myocardial infarction. Am J Cardiol.2010;105(3):312-7.
- Ye Z, Smith C, Kullo IJ: Usefulness of red cell distribution width to predict mortality inpatients with peripheral artery disease. Am J Cardiol.2011;107(8):1241-1245.
- Perlstein TS, Weuve J, Pfeffer A, et al: Red blood cell distribution width and mortality riskin a community-based prospective cohort. Arch Intern Med. 2009;169(6):588-594.
- Ijoma CK, Ulasi II, Anisiuba BC: Anemia predicts prolonged QT interval in predialysischronic kidney disease patients. The Intenet Journal of Cardiovascular Research 2010;7(1) :Doi: 10.5580/1d12
- Khode VH, Kammar KF: QTc changes in non-pregnant females with severe iron deficiencyanaemia. Journal of Clinical and Diagnostic Research.2012; 6(5):777-779.
- Zoppini G, Targher G, Chonchol M, et al: Anemia, independent of chronic kidney disease,predicts all-cause and cardiovascular mortality in type 2 diabetic patients. Atherosclerosis.2010;210:575-580.
- Mozos I, Serban C: The relation between QT interval and T-wave variables in hypertensivepatients. J Pharm Bioall Sci. 2011;3:339-44.
- Turrini P, Corrado D, Basso C, et al: Dispersion of Ventricular Depolarisation-Repolarisation. Circulation.2001;103:3075-80.
- Kumar R, Fisher M, Macfarlane PW: Diabetes and the QT interval: Time for debate. Br JDiabetes Vasc Dis. 2004;4:146-50.
- Szabo Z, Harangi M, Lorincz I, et al: Effect of hyperlipidemia on QT dispersion in patientswithout ischemic heart disease. Can J Cardiol. 2005;21(10):847-850.
- Andrassy G, Szabo A, Dunai A, et al: Acute effects of cigarette smoking on the QT intervalin healthy smokers. Am J Cardiol.2003;92(4):489-492.
- Pala AM, Ricciardelli D, Sanna A, Vinattieri MA: The effect of beta blockers on the QTinterval: the possible role of mechanisms other than beta block. Minerva Med.1989;80(12):1283-7.
- Macdougall IC: The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin. Nephrol Dial Transplant.1999;14:1836-1841.
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