Study design and setting
The present study was a case-control study conducted at the Centre Médical de Kinshasa (CMK) between January and December 2019. The CMK is a reference clinic that operates according to international standards and norms, with a cardiology unit named “Pôle de Cardiologie” (cardiology center), which is staffed by highly qualified and regularly retrained personnel. The cardiology unit provides cardiovascular explorations, such as Doppler echocardiography, coronary scanning, and cardiopulmonary exercise testing. A cardiovascular rehabilitation unit is also operational at this hospital and represents the only such unit in central Africa.
Consecutive asymptomatic hypertensive patients, aged 20 years or older, who attended the outpatient clinic of the CMK Pôle de Cardiologie between January and December 2019, were screened for clinical or laboratory evidence of secondary HTN and renal or hepatic disease. Patients in whom a cause of secondary HTN was found, as well as patients diagnosed with renal or hepatic disease, were excluded from this study. All other patients were invited to sign written informed consent forms to participate in this study and underwent cardiac Doppler ultrasound.
Participants with heart disease unrelated to high blood pressure (BP) were excluded from this study. Each participant who met the echocardiographic diagnostic criteria for LVH was matched for sex and age with two hypertensive patients without LVH.
A total of 267 participants were initially selected to participate in the study, including 106 with LVH and 161 without LVH. Of these, 47 were excluded for various reasons, including: dilated cardiomyopathy in 20 participants (8 with LVH and 12 without LVH); ischemic cardiopathy in 14 participants (5 with LVH and 9 without LVH); significant valvulopathy in 5 participants (2 with LVH and 3 without LVH); pericarditis in 5 participants without LVH; and hypertrophic cardiomyopathy in 3 participants with LVH. Therefore, the final analysis included 220 participants: 88 (40%) with LVH and 132 (60%) without LVH. The flow chart in Figure 1 summarizes the selection of cases and controls.
Anamnestic data were obtained using a standard questionnaire. The anamnesis focused on self-reported age, gender, sedentary behavior, alcohol use and smoking habits, history of diabetes mellitus, and current medication use to treat chronic diseases, especially antihypertensive drugs, anti-diabetic treatments, statins, antiplatelet agents, hypouricemics, oral contraceptives, and hormone replacement therapy. Participants were also asked to report their histories of cardiovascular events, including stroke, ischemic heart disease, heart failure, chronic kidney disease, and cardiovascular surgery.
The measurement of anthropometric parameters was performed by a final-year medical student who had previously undergone a practical training session for this purpose. Weight and height were measured using a validated electronic weight scale and a wall height gauge, respectively, while the participant was standing, barefoot, and lightly dressed. Body mass index (BMI) was calculated as the ratio of weight (kg) to height squared (m2). The waist circumference (WC) and hip circumference (HC) were obtained in cm using a tape measure.
The body surface area (BSA) was calculated using the DuBois formula , as follows:
BSA (m2) = 0.725 height (cm) × 0.425 weight (kg) × 0.00718413.
Blood pressure (BP) was measured non-invasively through 24-hour ambulatory blood pressure monitoring (ABPM) using a fully automatic recorder (Model TONOPORT V; GE Health care, Freiburg, GERMANY). The recorder was programmed to perform a BP measurement every 15 minutes during the waking period and every 30 minutes during sleep. The 24-hour average BP was used for these analyses.
In all participants, a detailed, two-dimensional, transthoracic echocardiography was performed by a single certified cardiac sonographer using a commercially available system (Vivid T8, GE Health care, Freiburg, GERMANY) equipped with a 3.5 MHz transducer. Left ventricular measurements were obtained, according to the 2015 American Society of Echocardiography and the European Association of Cardiovascular Imaging updated guidelines for cardiac chamber quantification . Measurements of left ventricular diameter (LVED), interventricular septum thickness (IVS), and posterior wall thickness (PWT) were measured at the end of diastole. Simultaneous ECG was performed to correlate the left ventricular measurements with the cardiac cycle. Left ventricular mass (LVM) was calculated according to the American Society of Echocardiography simplified cubed equation linear method, using the following equation: LVM (grams) = 0.8 × 1.04 × [(LVED + IVS + PWT)3 − (LVED)3] + 0.6 g, where LVED is the left ventricular end-diastolic diameter, IVS is the interventricular septal thickness, and PWT is the left ventricular posterior wall thickness. Left ventricular mass was indexed against BSA and height [2,7]. The relative wall thickness (RWT) was calculated as follows: (2 × PWT) / LVED.
In accordance with international recommendations , LV diastolic function was assessed from the apical four-chamber view, which included transmitral, pulsed-wave Doppler and mitral annular velocities with tissue Doppler echocardiography. The transmitral peak early (E) and peak late (A) diastolic velocities were recorded. The mitral annular early diastolic velocity (e’) was measured at the lateral mitral annulus using pulsed-wave tissue Doppler in the apical four-chamber view with gains minimized to allow for a clear tissue signal.
For all analyses, all participants provided a morning blood sample after an overnight fast. All samples were analyzed at the CMK laboratory. The blood for the determination of serum uric acid, total cholesterol (TC), LDL-c, HDL-c, and triglycerides was collected in a dry tube. The assay used to measure these biological parameters was performed using standard colorimetric methods, and the readings were performed using the HELIOS Epsilon brand colorimetric spectrophotometer (Milwaukee, USA). Glucose was assayed on oxalated plasma according to a colorimetric method using the “BIOLABO” test (France).
Insulinemia was assessed using ethylenediaminetetraacetic acid (EDTA) plasma by enzyme-linked immunosorbent assay (ELISA). The optical density reading was performed on a string read from HUMAREADER HUMAN (Germany).
Assessments of glycated hemoglobin (HbA1c) were performed using EDTA plasma by the electrophoretic method, with HYRYS HYDRASIS from SEBIA (France).
Serum creatinemia was measured by the simple colorimetric Jaffe method. Readings were assessed with a colorimetric spectrophotometer (Spectrum 2100 brand, South Africa).
Sedentary was defined as sitting for more than 7 hours a day . Cigarette smoking was defined as regular smoking for at least 30 days preceding the interview date, regardless of the number of cigarettes smoked .
Excessive alcohol consumption was defined as drinking more than 2 glasses of beer or its equivalent every day for at least a year .
Overweight was defined as a BMI between 25 and 29.9 kg/m2 of BSA .
Obesity was defined as a BMI equal to or greater than 30 kg/m2 of BSA . Abdominal obesity was defined as a WC greater than 102 cm for men and greater than 88 cm for women .
Poor control of arterial HTN was defined as an average systolic BP greater than 130 mmHg or an average diastolic BP greater than 80 mmHg, as assessed by 24-hour ABPM .
Diabetes mellitus was defined as a fasting blood glucose level ≥ 10 mmol/L and HbA1c > 7% .
Hyperinsulinemia was defined as fasting insulinemia > 90 mmol/L.
IR was defined as HOMA-IR ≥ 2.5 .
Dyslipidemia was defined as an HDL-c level of < 1.03 mmol/L for men and < 1.04 mmol/L for women, an LDL-c level ≥ 3.38 mmol/L, a TC level ≥ 5.17 mmol/L, or a triglyceride level ≥ 1.69 mmol/L .
The atherogenicity index (AI) was calculated as the TC-to-HDL-c ratio. The AI was considered high when this ratio was greater than 5 .
Hyperuricemia was defined as a fasting uric acid level > 420 mmol/L .
LVH was defined as LVM > 115 g/m2 or > 48 g/m2.7 for men when indexed to BSA or to height, respectively, and as LVM > 95 g/m2 or > 44 g/m2.7 for women when indexed to BSA or to height, respectively. Four LV geometric patterns were defined as follows : normal geometry (normal LVM and RWT ≤ 0.42), concentric remodeling (normal LVM and RWT > 0.42), eccentric hypertrophy (LVH and RWT ≤ 0.42), and concentric hypertrophy (LVH and RWT > 0.42).
Three patterns of diastolic dysfunction (DD) were defined according to the E/A ratio, as follows [41, 42]: abnormal relaxation (grade I DD: E/A ratio < 1 and prolonged deceleration time), pseudonormal relaxation (grade II: E/A ratio > 1 and intermediate deceleration time), and restrictive patterns (reversible and irreversible, grades III and IV, respectively; E/A ratio > 2 and shortened deceleration time).
Normal left ventricular filling pressure (LVFP) was defined by an E/e’ ratio < 8 . Elevated LVFP was defined by an E/e’ lateral > 12 
The dilation of the left atrium (LA) was defined as an LA body surface area > 20 cm2 .
Data are presented as the absolute (n) and relative (%) frequencies for categorical variables and as averages (± standard deviation) for quantitative variables. Paired comparisons between the cases and controls were performed using Pearson’s Chi-square test or Fisher’s Exact test, as appropriate, for categorical variables and using Student’s t-test for continuous variables.
Linear regression was used to determine the predictive factors associated with LVM variations. The following variables were entered in the univariate analysis: parameters of obesity (WC, HC, and BMI), parameters of glucose metabolism (fasting glucose, HbA1c, fasting insulinemia, and HOMA-IR), parameters of lipid metabolism (TC, HDL-c, LDL-c, and triglycerides), parameters of renal function (creatinine and uricemia), parameters of phosphocalcic metabolism (calcium, ionized calcium, and phosphorus). When significant associations were observed between LVM and these independent variables, the effects of potential confounders were studied by adjustment in multiple linear regression.
Simple logistic regression was used to determine which factors were predictive of LVH. The following variables were entered into the univariate analysis: Medical and social history (duration of HTN, cigarette smoking, excessive alcohol consumption, and menopause), sedentary lifestyle, uncontrolled HTN, dyslipidemia, high AI, diabetes mellitus, hyperinsulinemia, hyperuricemia, and IR. When associations were observed between LVH and these independent variables, the effects of potential confounders were studied by adjustment in a conditional logistic regression (multivariate analysis).
The significance threshold retained was p < 0.05. Statistical analyses were performed using XLStat 2020 and SPSS (Statistic Package for Social Sciences) software for Windows, version 24.
This research was conducted in strict compliance with the recommendations of the Helsinki Declaration III. Approval to conduct the study was obtained from the National Health Ethics Committee (No. 219 / CNES / BN / PMMF / 220). All respondents were debriefed on the results of the study.