|Year : 2021 | Volume
| Issue : 2 | Page : 44-50
Diagnostic usefulness of NT-proBNP in asymptomatic left ventricular dysunction in black hypertensive patients
Atinuke O K Richard1, Folasade Adeola Daniel2, Phillip Alaba Adebola2, Olayinka O Ogunleye3, Ayodele O Ekun4
1 Department of Medicine, General Hospital Odan Lagos, Departments of Medicine, Ikeja, Lagos, Nigeria
2 Lagos State University Teaching Hospital; Lagos State University College of Medicine, Ikeja, Lagos, Nigeria
3 Lagos State University Teaching Hospital; Department of Pharmacology, Therapeutics and Toxicology, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria
4 Lagos State University Teaching Hospital; Department of Medical Laboratory Sciences, Lagos University College of Medicine, Ikeja, Lagos, Nigeria
|Date of Submission||09-Dec-2020|
|Date of Decision||26-Dec-2021|
|Date of Acceptance||09-May-2022|
|Date of Web Publication||10-Dec-2022|
Dr. Folasade Adeola Daniel
Department of Medicine, Lagos State University, College of Medicine, Ikeja
Source of Support: None, Conflict of Interest: None
Background: Hypertensive patients with left ventricular (LV) dysfunction, may be asymptomatic early in the disease process but tend to develop overt heart failure later on. While the usefulness of NT-proBNP in the early detection of LV dysfunction has been well studied among the Western population, there remains a relative paucity of information about its usefulness among black hypertensive patients. The aim of this study was to determine the diagnostic usefulness of NT-proBNP in the early detection of asymptomatic LV dysfunction in black hypertensive patients.
Methodology: The LV function of 134 patients with hypertension who were never in heart failure and 89 age- and sex-matched normotensive individuals were assessed using echocardiography and serum NT-proBNP assay. However, due to various factors (such as drop out and abnormal laboratory results), 131 hypertensives and 79 controls were eventually analyzed. Echocardiography was used as gold standard in determining LV functions. NT-proBNP levels were measured using enzyme-linked immunosorbent assay. Data obtained were summarized with appropriate descriptive and inferential statistics at a 5% level of significance using the Statistical Package for the Social Science (SPSS) Version 22.0 software.
Results: Asymptomatic LV dysfunction was present in 107 hypertensive individuals (81.7%): 102 (77.9%) had isolated diastolic dysfunction and 5 (3.8%) had combined diastolic and systolic dysfunction; whereas the remaining 24 patients (18.3%) had normal LV function. NT-proBNP were 175.21 ± 227.75 and 430.13 ± 491.88 pg/ml, P = 0.017, in hypertensive individuals without and with asymptomatic LV dysfunction, respectively. Using the NT-proBNP level of 56 pg/ml obtained among the controls, NT-proBNP level had a sensitivity of 62.8% and specificity of 60.9%. NT-proBNP level also had a positive predictive value of 88.0% and negative predictive value of 26.4%.
Conclusion: NT-pro-BNP could be incorporated as a screening tool for early detection of asymptomatic LV dysfunction and possibly, stratify patients for further evaluation and treatment.
Keywords: Asymptomatic left ventricular dysfunction, echocardiography, hypertension, NT-proBNP
|How to cite this article:|
Richard AO, Daniel FA, Adebola PA, Ogunleye OO, Ekun AO. Diagnostic usefulness of NT-proBNP in asymptomatic left ventricular dysunction in black hypertensive patients. Nig J Cardiol 2021;18:44-50
|How to cite this URL:|
Richard AO, Daniel FA, Adebola PA, Ogunleye OO, Ekun AO. Diagnostic usefulness of NT-proBNP in asymptomatic left ventricular dysunction in black hypertensive patients. Nig J Cardiol [serial online] 2021 [cited 2023 Feb 7];18:44-50. Available from: https://www.nigjcardiol.org/text.asp?2021/18/2/44/363145
| Introduction|| |
Asymptomatic left ventricular dysfunction (ALVD) is a well-recognized preclinical stage of heart failure that is highly prevalent among hypertensive patients, with a substantial proportion of these patients eventually developing symptomatic heart failure., Heart failure is a major public health problem worldwide which imposes escalating financial, material, and human resources burden on health-care systems. Several hospital-based studies in Nigeria found heart failure as the major cause of medical admissions with a varying prevalence of 30.5% to 44.3%., Previous data from the Southwestern part of the country found heart failure to be the most prevalent disorder among patients diagnosed with cardiovascular disease over a 5-year period, with a prevalence of 35%. Heart failure carries a high mortality rate despite currently available therapies. In the Framingham Study, the median survival rate of patients with heart failure was 1.7 years for men and 3.2 years for women. Survival studies in Nigerian patients with heart failure also reported a high mortality rate., Isezuo et al., in a study of 52 Gambians and 55 Nigerians heart failure patients, reported overall 1-year survival rate of 71%. Familoni et al. reported 3-year survival rate of 32.1% in their study. In view of this bleak prognosis, primary prevention, earlier recognition, and prompt diagnosis of heart failure are therefore undoubtedly a priority.
Brain natriuretic peptide (BNP) has a well-established role in the diagnosis and prognostication of heart failure., Evidence is also emerging on its usefulness in guiding therapy and screening for asymptomatic disease. BNP is a cardiac biomarker and its level increases when myocytes are strained as a result of volume expansion and pressure overload., The levels of BNP are known to be elevated in patients with left ventricular (LV) dysfunction. The high negative predictive value of BNP tests is particularly helpful in ruling out a diagnosis of LV systolic dysfunction LVSD.,, The European Society of Cardiology guidelines for the diagnosis and treatment of heart failure recommend measurement of BNP in the assessment of heart failure patients, especially in low-resource settings. Despite this recommendation, BNP is still being largely underutilized in the assessment of heart failure patients in Nigeria, unlike in the case of developed countries., There are a limited number of published works on BNP among Nigerian patients and these were mainly in patients with overt heart failure., This study was therefore aimed at evaluating the usefulness of BNP as a screening tool for ALVD and early detection of heart failure in hypertensive patients seen in a tertiary hospital in Western Nigeria. This was with the hope of achieving reduction in morbidity and mortality, through early intervention.
| Methodology|| |
The study was a descriptive cross-sectional study carried out at the Lagos State University Teaching Hospital, a tertiary health center located in Ikeja, Lagos State. Consecutive patients with hypertension attending the medical and general outpatient clinics of the hospital who met the inclusion and exclusion criteria were recruited for the study. The inclusion criteria were age between 18 and 70 years, known hypertensive on treatment or patients with systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg and who were asymptomatic for heart failure. The exclusion criteria were patients with a history of breathlessness or any underlying/established cardiac disease apart from systemic hypertension, history of renal failure or (plasma creatinine value >2.0 mg/dl), liver disease or elevated ALT/AST >65u/l and/or low albumin <28 g/l, history of cigarette smoking, morbid obesity (Body Mass Index (BMI) ≥40 kg/m2), secondary hypertension, history of diabetes mellitus or fasting blood glucose level >126 mg/dl or random blood glucose level >200 mg/dl. A total of 134 asymptomatic hypertensive patients and 89 age- and sex-matched normotensive individuals were enrolled in the study. Institutional ethical approval and individuals informed consent were obtained before the individuals were enrolled in the study.
A structured questionnaire was used to obtain the biodata and clinical history of patients who met the inclusion and exclusion criteria. Patients' weight and height were measured according to standard recommendations and BMI was calculated based on: BMI = Weight (kg)/Height (m2). Morbid obesity was defined as a BMI ≥40 kg/m2. Blood pressure readings were measured according to standard recommendations, using a mercury sphygmomanometer with an appropriate cuff size. Hypertension was defined as an SBP ≥ 140 mm Hg and/or a DBP ≥90 mm Hg or current use of antihypertensive medications.
Measurements of serum BNP and other biochemical parameters
A volume of 8 ml of venous blood sample was taken for biochemistry (alanine transaminase, aspartate transaminase, total protein, albumin, urea, and creatinine) and NT-porBNP measurement. NT-proBNP was measured using a laboratory-based assay that uses a fully quantitative enzyme immunoassay method.
Baseline transthoracic echocardiography was carried out on the participants on the same day that the blood sample was taken. Standard M-mode and two-dimensional echocardiography were performed with patients in the left decubitus position using GE Healthcare Vivid q cardiovascular ultrasound system. Measurements were obtained according to the recommendations on M-mode standardization of the American Society of Echocardiography. Measurements were taken in three cardiac cycles and the mean was calculated. All measurements were made at end-diastole.
LV hypertrophy was considered present when indexed LV mass exceeds 115 g/m2 in men and 95 g/m2 in women.
Diastolic function was categorized as Normal (E/A 1–2; deceleration time (DT) 150–240 ms; isovolumic relaxation time [IVRT] 80–110 ms), impaired relaxation pattern (E/A <1; DT > 240 ms; IVRT >110 ms), pseudo normalization pattern (E/A 1–2; DT 150–240 ms; IVRT 80–110 ms) restrictive pattern (E/A >2; DT <150 ms; IVRT 80–110 ms) E/A: ratio of mitral inflow early rapid peak velocity to late atrial peak velocity, DT; IVRT. A reversal of pseudo normal to impaired relaxation pattern with valsava maneuver was used to differentiate normal diastolic function from pseudo normalized pattern of diastolic dysfunction. Tissue Doppler imaging would have been used to further characterize the diastolic function; however, the application was not available on the echocardiograph used for the study.
Endocardial fractional shortening (FS) was calculated from LV internal dimensions in systole and diastole using the formula: FS = (LVIDd − LVIDs)/LVIDd × 100%. LV ejection fraction (LVEF) was calculated using derived volumes by Teichholz formula based on M-mode LV dimensions. LV volume = 7/(LVID + 2.4) × (LVID). The criteria for depressed LV function was based on FS <29%, and EF ≤50%. The grading for systolic function will be classified as follows – Normal LV systolic function – EF= ≥50%, Mild LV systolic dysfunction – EF = 40%–49%, Moderate LV systolic dysfunction EF = 30%–39%, and Severe LV systolic dysfunction EF <30%
The data were analyzed using the Statistical Package for the Social Science (SPSS Version 20.0). Quantitative data were reported as mean ± standard deviation and qualitative data were expressed as percentages. Means were compared using Student's t-test and ANOVA as appropriate. In addition, the sensitivity and specificity of NT-proBNP in identifying ALVD were determined as stated below:
Sensitivity - TP/(TP + FN) × 100 and Specificity - TN/(TN + FP) × 100.
where: TP = True positives; TN = True negatives; FN = False negatives and FP = False positives.
True positives are cases with elevated BNP values and echo confirmed parameters of LV dysfunction. True negatives are cases with normal BNP values and echo confirmed parameters of normal LV function. False negatives are cases with normal BNP values, but the presence of LV dysfunction on echocardiography. False positives are cases with elevated BNP values, but the finding of normal LV function on echocardiography. Furthermore, positive predictive value-PV (+ve) and negative predictive value-PV (-ve) of NT-proBNP as a screening test will be determined as follows-PV (+ve) = TP/(TP + FP) × 100 and PV (−ve) = TN/(TN + FN) × 100.
| Results|| |
A total of 229 participants consisting of 140 hypertensive patients and 89 age- and sex-matched controls, were recruited into the study. However, due to various factors (such as drop out, abnormal laboratory results, etc), 131 hypertensives and 79 controls were eventually analyzed. Of the 131 hypertensives used in the research, 55 (42.0%) were males while 76 (58.0%) were females, whereas 30 (42.8%) were males and 40 (57.2%) were females in the controls group. The mean age of both hypertensive patients and controls was similar (53.64 ± 10.32 vs. 53.01 ± 11.17 years, P = 0.679). The mean age of hypertensive patients with ALVD was found to be significantly higher than those without dysfunction (43.17 ± 8.47 vs. 55.90 ± 9.28, P < 0.001). The mean BMI was significantly higher in hypertensive patients compared to controls (28.73 ± 4.12 vs. 26.65 ± 5.52, P = 0.004). Mean systolic and DBPs; and pulse rate were significantly lower in controlswhen compared with hypertensive patients with P < 0.001.
NT-proBNP level in hypertensive patients was much higher than in controls (390.33 ± 464.68 vs 55.58 ± 40.09, P < 0.001). Mean urea and creatinine were much higher in hypertensive patients when compared with their values in the control group (5.16 ± 2.11 vs. 3.61 ± 1.16, P < 0.001 and 96.95 ± 29.46 vs. 76.20 ± 17.77, P = 0.001, respectively). Baseline characteristics and biochemical parameters of subjects and controls are shown in [Table 1].
|Table 1: Baseline characteristics and biochemical parameters of hypertensive patients and controls|
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A total of 107 (81.7%) hypertensive individuals had asymptomatic LV dysfunction, whereas the remaining 24 (18.3%) had normal LV function. Majority of the hypertensive individuals 102, (95.3%), with asymptomatic LV dysfunction had isolated LVDD, while only 5 (4.7%) patients had both asymptomatic LV systolic dysfunction and LV diastolic dysfunction. Mild (Grade 1) diastolic dysfunction was found in 58.8%, moderate (Grade 2) diastolic dysfunction in 22.1%, and only one subject with severe (Grade 3) diastolic dysfunction constituting 0.8%. [Table 2] shows the LV echocardiographic parameters and NT-proBNP levels in hypertensive individuals with normal LV function compared to that of hypertensive patients with asymptomatic LV diastolic dysfunction.
|Table 2: Echocardiographic parameters and N-terminal pro-brain natriuretic peptide levels in the two hypertensive subgroups|
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The duration of hypertension was noted to differ significantly between the two hypertensive subgroups (P = 0.003). Hypertensive individuals with no LV dysfunction recorded a lower duration of hypertension (3.07 ± 3.32 years) compared with a duration of 9.21 ± 8.89 years recorded among hypertensives with ALVD. Hypertensive patients with ALVD had thicker IVS and LVPW in both systole and diastole compared to those without ALVD. The difference was statistically significant with P = 0.003 and 0.001 for IVS; 0.001 and 0.008 for LVPW, respectively. Similar pattern was noted in LVDD, AO, RWT, and LVMI values, whereas the reverse was true for the E/A ratio which was found to be significantly lower in hypertensives with ALVD. The mean LVEF and FS were normal and comparable in both subgroups of hypertensive individuals.
The findings showed that hypertensive patients with isolated LV diastolic dysfunction had NT-proBNP level that was significantly higher than hypertensive individuals with normal LV function (409.09 ± 480.63 vs. 175.21 ± 227.75). Among patients with ALVD, the highest mean value of NT-proBNP was found in hypertensive patients with combined asymptomatic systolic and diastolic dysfunction, compared to those with isolated asymptomatic LV diastolic dysfunction only (430.13 ± 491.88 vs. 409.09 ± 480.63). Hypertensive individuals with LV systolic dysfunction had the highest level of NT-proBNP. These data are summarized in [Table 3]a and [Table 3]b. All the different types of asymptomatic LV dysfunction were noted to have higher NT-proBNP compared to hypertensives without dysfunction.
Using cut-off value of 56.0 pg/ml obtained among controls as normal NT-proBNP level, the sensitivity and specificity was: Sensitivity = TP (TP + FN) × 100 = 66/(66 + 39) × 100 = 6600/105 = 62.8%. Specificity = TN/(TN + FP) × 100 = 14/(14 + 9) × 100 = 1400/23 = 60.9%. The obtained echocardiographic parameters of LV functions were taken as true positives. The calculation showed that NT-proBNP is moderately sensitive and specific for the detection of asymptomatic LV dysfunction in hypertensives. The positive and negative predictive values of NT-proBNP in detecting ALVD in hypertensive patients who were asymptomatic for heart failure using cut-off value of 56.0 pg/ml were as follows:
PV(+ve) = TP/(TP + FP) × 100 = 66/66 + 9 × 100 = 88.0%. PV (−ve) = TN/(TN + FN) × 100 = 14/14 + 39 × 100 = 26.4%. The calculation showed that NT-proBNP had a strong positive predictive value, but low negative predictive value [Table 4].
|Table 4: Sensitivity and specificity of N-terminal pro-brain natriuretic peptide in detecting asymptomatic left ventricular dysfunction in hypertensive patients|
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| Discussion|| |
The study was aimed at determining the diagnostic usefulness of NT-proBNP in the early detection of asymptomatic LV dysfunction in Nigerian patients with systemic hypertension. The mean age of hypertensive and controls in the study was 54 years and 53 years, respectively. The age recorded in our environment is much lower than that recorded in studies done in California and Italy with mean ages of 68.8 ± 11.7 and 66.4 ± 7.8 years, respectively., The lower age in this study population might be due to a higher risk of developing hypertension at an earlier age among blacks compared to Caucasians. The present study showed that the mean plasma levels of NT-proBNP were significantly higher in hypertensive patients with ALVD compared to hypertensives without LV dysfunction (430.13 ± 491.88 vs. 175.21 ± 227.75, P = 0.017). This finding is similar to that reported by Vikas Bhalla et al., in California and Betti et al., respectively, in Italy among patients at risk for heart failure., They recorded a higher level of NT-proBNP among high-risk hypertensive patients with LV dysfunction. The usefulness of NT-proBNP in detecting asymptomatic LV dysfunction is well established amongst Caucasians.,,,,, Results from the Dallas Heart Study also revealed a better performance of NT-proBNP in detecting LVH or LV systolic dysfunction in subjects at high risk for heart failure. Ajuluchukwu et al., in a Nigerian study on NT-proBNP in heart failure, showed that NT-proBNP rises significantly in both systolic and diastolic heart failure. Similar results were reported by Gbadamosi et al., at the University of Ilorin Teaching Hospital, Kwara State, Nigeria.
The study further demonstrated that NT-proBNP level increases significantly with increasing severity of diastolic dysfunction. The highest value was recorded among patients with moderate-to-severe diastolic dysfunction. This is partly, in keeping with the findings of Lang et al., which showed that BNP was raised in patients with isolated diastolic dysfunction. However, the level of rise was not conmesurate with the severity of diastolic dysfunction in that study. Troughton et al., in their study, found that plasma BNP levels increase significantly according to the severity of overall LV diastolic dysfunction, as it progresses from abnormal relaxation to pseudonormal and restrictive filling pattern. Similar finding was reported by the PROBE-HF study. However, the PROBE-HF study was only able to establish a significant relationship between NT-proBNP and moderate-severe-diastolic dysfunction, but not with mild diastolic dysfunction. On the contrary, Ojji et al., in their study on the proposed role of NT-proBNP in assessing cardiac remodeling in hypertensive African individuals, did not find any relationship between LV diastolic dysfunction and NT-proBNP levels in hypertensives. In his study, Ojji studied patients with LV hypertrophy and those with hypertensive heart failure; there was no selection of patients before echocardiography. Romano et al., in a similar study among diabetic patients, found that BNP correlated with diastolic dysfunction amongst uncontrolled diabetic patients. Bursi et al., in their study of systolic and diastolic heart failure in the community, demonstrated that diastolic dysfunction is independently related to levels BNP.
NT-proBNP is a fragment of brain natriuretic peptide prohormone that is released from cardiac myocytes in response to multiple pathologic stimuli. Such stimuli include LV hypertrophy, increased wall stress, pressure overload, and ventricular volume expansion. The findings of the current study suggest that measuring NT-proBNP levels may be a useful way to identify hypertensive patients with asymptomatic LV dysfunction. It might also possibly be used to stratify patients according to the severity of the dysfunction.
Sensitivity and Specificity of NT-proBNP
The sensitivity and specificity of NT-proBNP for ALVD were found to be 62.8% and 60.9%, respectively, using the NT-proBNP level of 56 pg/ml obtained among the controls. The study also showed that NT-proBNP has a high positive predictive value of 88.0%, but low negative predictive value of 26.4%. Betti et al. reported a sensitivity of 87.5%, specificity of 92.7%, negative predictive value of 100%, and positive predictive value of 32.5% in their study. Ajuluchukwu et al., and Gbadamosi et al., in their studies of BNP in heart failure patients, recorded high specificity and sensitivity of BNP for heart failure (85.7% sensitivity and 93.3% specificity vs 96.2% sensitivity and 74.8% specificity), respectively., The relatively lower specificity and lower sensitivity observed in this study compared to that of Ajuluchukwu et al., and PROBE-HF study could be due to differences in population characteristics., The PROBE-HF study had a much larger sample size (n = 1012) and a relatively older population (mean age = 66.4 ± 7.8 years). The study by Ajuluchukwu et al. was amongst heart failure patients, while the current study was done among hypertensives, who were asymptomatic for heart failure. The low negative predictive value obtained in the study could be due to the high prevalence of ALVD in the hypertensive cohort studied. Rodeheffer in his review article on measuring BNP in heart failure, showed that BNP has a good negative predictive value when the prevalence of the study entity in the cohort is low. When the prevalence is higher, positive predictive value is improved at the expense of a lower negative predictive value. Mahmoud et al. had also shown in their study that BNP and NT-pro BNP had comparable diagnostic values in the diagnosis of cardiac failure and that a BNP <200 pg/ml and an NT-proBNP <1000 pg/ml had excellent negative predictive values for excluding cardiac failure.
| Conclusions|| |
NT-proBNP was elevated in patients with asymptomatic LV dysfunction and its level was commensurate with the degree of dysfunction. NT-proBNP had a high positive predictive value of 88.0%, moderate sensitivity 62.8%, and moderate specificity 60.9% in detecting patients with asymptomatic LV dysfunction. The negative predictive value was low (26.4%). Hypertensive patients could be screened for asymptomatic LV dysfunction using NT-proBNP as a surrogate marker.
A larger sample size could not be studied because of the huge financial burden involve in procuring reagents for NT-proBNP and other reagents for the other biochemical parameters. The echocardiography machine did not have a facility for tissue Doppler, which could have enhanced the evaluation of LV diastolic dysfunction in the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]