CRCM Journal

Introduction

Heart failure (HF) affects up to one in five adults during their lifetime and is associated with considerable mortality and morbidity, despite advances in management [1-3]. Although most of the burden of HF is borne by people aged 65 or older, study reports show an increase in the incidence of HF, especially in younger people [4,5].

Diabetes mellitus (DS) is a progressive and chronic metabolic disorder characterized by insulin resistance and functional failure of pancreatic beta cells [6, 7]. The prevalence of DS has increased intensely over the past decades, with the highest growth rates observed in sub-Saharan Africa [8,9].

The most deleterious consequence of DS is the considerable high risk of developing IC. Diabetic patients have up to 74% increased risk of developing HF and are likely to die [10]. The link between DS and HF is now the subject of many studies in the West and is less so in sub-Saharan Africa, yet DS is a major risk factor for HF [11].

In addition to conventional cardiovascular risk factors leading to the development of HF, individuals with DS are more vulnerable due to the contributing influence of diabetes-related risk factors including chronic hyperglycemia, insulin resistance and collagen deposition in the myocardium, ultimately leading to the so-called “diabetic cardiomyopathy”, resulting in left ventricular and diastolic dysfunction [12]. Other than traditional cardiovascular risk factors, diabetic retinopathy (DR) is another common microvascular complication and is associated with cardiovascular events such as stroke, heart failure, and coronary artery disease in patients with type 1 and type 2 diabetes [13]. The elevated risk of HF in diabetic patients compared to non-diabetic patients underscores the need for cardiovascular risk screening in asymptomatic diabetic patients on the premise that earlier identification and stratification would lead to appropriate management of the disease. risk of long-term and short-term heart failure [14]. There is a dearth of comprehensive data on the determinants of HF in patients with diabetes in the Democratic Republic of Congo, particularly in Goma, North Kivu. This study was therefore conducted to assess the determinants of heart failure in patients with diabetes mellitus followed in Goma.

Patients and methods

The study was carried out at the Center of the Association of Diabetics in Congo (ADIC) in Goma, DRC. This site was selected on the basis of a reasoned choice based on the age of the center and the number of diabetic patients seen in one week. This was a crosssectional and analytical study including all known asymptomatic diabetics in the city of Goma during the period from February 5 to 19, 2023.

The study population consisted of all diabetics who consulted the ADIC Center and those from other hospitals during the study period; after raising awareness in their WhatsApp groups and on the radio. The sample size was calculated from Fisher’s formula: n ≥ (Z^2 x(p)(1-p))/d^2 where n = Sample size, z = 1.96 (confidence coefficient), p = previous prevalence, d = 0.05 (margin of error or range of imprecision reflecting the desired degree of absolute precision). The probability of the risk of IC in diabetics being not yet elucidated in our country, we prefer to take 50% which is the median where the phenomenon is better distributed. So p=0.5 was the prior prevalence used in all studies to calculate the sample size. So the calculated sample size is n≥(1.96)2x0.5x0.5/(0.05)2=384. By incorporating the 10% of non-respondents, we obtain 422 diabetics to be included. During the data collection period in this Center, 408 diabetics met the inclusion criteria.

The selection was made on free informed consent and recorded in writing. The inclusion criteria were asymptomatic diabetic status, residence in the city of Goma and age between 18 years minimum and 90 years maximum. The criteria for non-inclusion included diabetic complications including heart disease undergoing treatment, diabetics on dialysis, with serious complications related to diabetes mellitus.

Data collection was done using a form pre-established by our research group. The parameters of interest were retained and collected by way of questioning for the ethnic group, sex, age and by way of clinical and paraclinical examinations for the anthropometric, biochemical and hemodynamic parameters measured by the equipment indicated in following paragraphs.

Anthropometric data were measured for weight and height using the scale coupled with the Health O meter® brand height rod, model 500KL, SN 5000155271, DATE CODE: 3718, Made in China. A millimeter tape measure was used to measure waist circumference (TT) and hip circumference (TH). Systolic (PAS) and diastolic (PAD) arterial pressures (BP) were measured using an OMRON model M2 Basic electronic blood pressure monitor (HEM-7120-E). The electrocardiogram (ECG) was recorded by a Comen brand device, Model: CM 1200B, SN 92190522018B, manufactured on May 22, 2019, connected to the electric generator, after explaining the technique to the patient, he lies down on the bed examination in dorsal decubitus, undressed in the thorax and shoes, calm. After the identification of the patient, the application of the gel to the sites, the electrodes are placed on the thorax and the limbs, and then an electrocardiogram is printed. The Peguero index was used to look for left ventricular hypertrophy. The electrocardiograms were interpreted by a single cardiologist for better and uniform results.

Biological data included blood data. The venous blood was taken at the level of the fold of the elbow on dry tubes and EDTA tubes for the various analyses, 5ml of venous blood taken was put on an EDTA tube for the analyzes of glycated hemoglobin, BNP, hsTroponine and hs- CRP. The dry tubes were used for analyzes such as NT-proBNP, Creatinine, Total cholesterol, Cholesterol-HDL, Triglycerides and LDL-cholesterol. The packaging of the samples included first an absorbent paper, an appropriate Biohazard brand specimen transport bag, then in the isothermal container containing the ice packs. All the samples were stored in a blood bank type refrigerator, brand XY130 (in China) between 2 to 4°C. The tubes for biochemical analyze (total-cholesterol, HDL, LDL, creatinine and, triglycerides) were made on a spectrophotometer brand RAYTO 9200 Semi-auto chemistry Analyzer, SN: 602321157 IE (Rayto, Guangming in China). For glycemia was carried out after ring finger disinfection with a brand glucometer 2019TRUE METRIX®Meter,SERIAL:T07123273,LOT:KX0747,EXP DATE:2025-02-06. The dosage of glycated hemoglobin is carried out on whole blood collected on EDTA K2 anticoagulant by nephelometry method on Genrui PA120 Fully-auto Specific Protein Analyzer.SN: 1141030201223, REF 31000003.

Place the three reagents including the 20 ml diluent, the 15 ml latex and the 5 ml anti serum in the machine according to their programmed position in the machine, then you will have to read the Mag card for each Kit (which contains the reagent information), introduce the patient’s identity by the patient’s number then save, present the whole blood sample to be well homogenized to the probe of the machine and click on the start button, the machine allows 20 µl to be aspirated of the sample, the machine will automatically start the analysis by pipetting the three different reagents and the result appears on the screen of the machine in 60 seconds in a quantitative way in percentage whose reference value is from 4.2-6.5%.

The results were interpreted according to the threshold of reference values containing reagents on each kit as follows: blood sugar had a reference value of 70-110mg/dL, creatinine 0.5 to 1.3mg/ dL, total cholesterol <200mg /dL, HDL-c >55mg/dL for men and >65mg/dL for women, LDL-c <100mg/dL, Triglycerides<150mg/ dL (Figure 1).

Figure 1: Presentation of sampling tools and biochemical analyzes

In order to guarantee the accuracy of the results, the CIMAK laboratory carried out a commercial internal quality control (IQC) (freeze-dried serum to be reconstituted). These checks were carried out and validated each morning, and adapted to regulatory requirements. ELITROL I (normal references) and ELITROL II (pathological references) control sera were used. CQI results were interpreted taking into account Westgard rules and Levey-Jennings charts. Appropriate corrective measures were taken whenever the values fell outside the defined limits. Depending on the case, these measurements concerned the IQC serum and/or the automaton and/or the reagents and/or the calibration.

The following definitions were used in this work:

Hypertension was defined, for some studies, by blood pressure (BP) taken in the office, including systolic ≥ 140 mmHg and/or diastolic ≥ 90 mmHg and/or the presence of a personal history of hypertension [15]. Diabetes mellitus was defined by the following criteria: a fasting blood glucose level ≥ 126 mg/dl (7.0 mmol/l) and/or a personal history of known diabetes mellitus and/or a glycated haemoglobin level ≥ 6.5% (48 mmol/mol) [16]. Smoking by cigarette will be defined by a regular intake of tobacco by cigarette for at least 30 days before the present study, regardless of the number of cigarettes [17]. Excessive alcohol consumption will be defined by taking more than 2 glasses of beer/day or an equivalent for at least a year [18]. Overweight will be defined by a BMI ≥ 25 kg/m2, overweight by a BMI between 25 and 30 kg/m2 and overall obesity by a BMI ≥ 30 kg/m2 [19]. Abdominal obesity was defined by a TT > 94 Cm for men and > 80 Cm for women [20]. Dyslipidaemia was defined as HDL cholesterol level <1.03 mmol/L for men or <1.04 mmol/L for women, LDL cholesterol level ≥ 3.38 mmol/L, total cholesterol level ≥ 5.17 mmol/L and/ or a triglyceride level ≥ 1.69 mmol/ [21]. The incidence of heart failure in diabetics was defined with a pulse pressure ≥65mmHg [22]. The ophthalmological evaluation will be carried out by examination of the retinography, using an Intucan45, SN: AAIVL 19008, Model: GSM36E12, Made in China taking the 45-degree image of the retina. Image acquisition was performed by an experienced operator. Each patient had two images for each eye, one centered on the papilla and the other on the macula. Intraocular pressure was measured using an Icare TA01i rebound tonometer (normal intraocular pressure varies between 10 and 22 mmHg). The elements sought were diabetic macular edema (DME) including retinal thickening and/or lipid exudate in the macular region, diabetic retinopathy (vascular and cellular damage). Diabetic macular edema is defined by the presence of retinal thickening and/or fluid accumulation in the macular region. Diabetic retinopathy was defined by deterioration of retinal vessels and cells using the international classification of the American Society of Ophthalmology (AAO).

Statistical analyses

The data was compiled in an Excel 2010 database and then transferred to SPSS for Windows version 25 software for analysis. Descriptive statistics were presented as mean (plus or minus standard deviation) for continuous variables with normal distribution and as median (IQS: Interquartile Space) for continuous data with non-Gaussian distribution. The normality test (Kolmogorov-Smirnov or Shapiro-Wilk) was used to differentiate normally distributed and non-normally distributed quantitative variables. Absolute (n) and relative (%) frequencies were expressed for categorical variables. Student’s t-test, Mann-Whitney U-test, and Pearson’s chi-square or Fischer’s exact test were performed, respectively, to compare means, medians, and proportions in the two groups. Logistic regression was used to find the determinants of the incidence of heart failure in univariate and multivariate analysis with calculation of the OR and their 95% confidence interval. Two final models were developed by identifying collinear variables (gender and menopause). The VIF coefficient (variance inflation factor) made it possible to identify the collinear variables, a value of VIF greater than 10 indicated a high multi-collinearity between the factors. For all the tests used, the value of p < 0.05 was considered as the threshold of statistical significance.

Ethical considerations

Before the start of this study: the protocol was submitted for approval by the Medical Ethics Committee of the University of Goma at No. UNIGOM/CEM/09/2022. Informed consent must be obtained from the patient. During the course of the study, we will conduct our study based on the 3 main principles of ethics, namely: respect for the human person, benevolence and justice.

Results

Figure 2 illustrates the flow of participants in the present study where, out of 450 diabetics who responded to the call launched at Center ADIC, 20 were not included in the study for the following reasons: not being a resident of Goma, followed for IC and presenting with visible pregnancy. Of the 430 diabetics included in the study, 22 were excluded for not having carried out an ECG and the entire assessment. At the end of the study, the sample analyzed is 408 (Figure 2).

Figure 2: Participant Flowchart

Heart failure incidence

Of a total of 408 diabetic patients examined, 122 had an incidence of heart failure, a frequency of 29.98% (Figure 3).

HF: heart failure

Figure 3: Distribution of patients according to incidence of heart failure

In Figure 4, we note that women had a significantly higher proportion of incidence of insufficiency than men (33.9% vs 24.3% in men, p = 0.023). The same figure shows that patients with type 2 diabetes mellitus had a significantly higher proportion of incidence of heart failure than those with type 1 (p<0.001).

DM : Diabete Mellitus

Figure 4: Frequency of incidence of heart failure by sex and type of diabetes

By comparing the subjects with incidence of HF to those without incidence of HF ; we note that the patients with incidence of HF included a greater proportion of women, subjects with stroke, and with a background of pathological eye. Mean values of subjects with incidence of heart failure were higher than those with no incidence of heart failure for age, SBP, DBP, MBP, PP, HR, BMI, circumference hip and WC/Waist ratio (Table 1).

Table 1: Clinical characteristics according to incidence of heart failure

The comparison of cardiovascular risk factors in diabetics with incidence of heart failure with those without incidence of heart failure had shown that diabetics with incidence of heart failure had a higher frequency of subjects over 40 years of age, hypertension, type 2 diabetes mellitus, physical inactivity, menopause, stroke, obesity and metabolic syndrome (Table 2).

Table 2: Traditional risk factors according to the incidence of HF

HTA : Hypertension artérielle, DS : Diabète sucré, AVC : Accident vasculaire cérébral, RAH : rapport hauteur hanche, RCM : Risque cardiométaboliques.

With regard to (Table 3), we note that diabetic subjects with incidence of heart failure had a very high mean or median for Hb1AC, total cholesterol, creatinine than their counterparts who had no incidence of heart failure. cardiac. The proportion of Hb1AC ≥7%, CT ≥185 mg/dl and eGFR <60 ml/min/1.73m² were higher in diabetic subjects with incidence of heart failure.

HbA1c: Glycosylated hemoglobin, eGFR: Estimated glomerular filtration rate, NYHA: New York Heart Association; BNP: Bread Natriuretic Peptide, LDL-c: Low density lipoproteins cholesterol; HDL-c: High Density lipoproteins cholesterol, TC: Total Cholesterol.

Table 3: Biological characteristics according to incidence of heart failure

By introducing alone to test the association between the incidence of heart failure and the independent variables, it was noticed that only age ≥40 years, female gender, hypertension, type 2 diabetes mellitus, physical inactivity, obesity, menopause, Hb1AC≥7%, hypercholesterolemia, eGFR<60 ml/min/1.73m² and pathological FO were directly associated with the incidence of HF.

In multivariate analysis, adjusted for all these variables in multivariate without introducing sex into the model (model 1), hypertension (aOR: 5.93 95% CI: 2.42-14.51), SD type 2 (aOR: 3.60 95% CI: 1.63-4.25), menopause (aOR: 5.48 95% CI: 3.03-9.72) and eGFR<60 ml/min/1.73m² (ORa: 348 95% CI: 1.94-5.30) were the independent determinants of heart failure incidence.

In model 2 without introducing menopause, female gender (aOR: 2.80 95% CI: 1.06-3.80), hypertension (aOR: 3.99 95% CI: 2.16-7.41), DS type 2 (aOR: 5.72 95% CI: 1.77-8.52), eGFR <60 ml/min/1.73m² (aOR: 3.10 95% CI: 1.87-5.09) and fundus pathology (aOR: 2.04, 95% CI: 1.77-5.35) were the independent determinants of the incidence of heart failure (Table 4).

HTA: Hypertension; DM: Diabetes Mellitus, HbA1c: Glycosylated Hemoglobin, eGFR: Estimated Glomerular Filtration Rate, TC: Total Cholesterol, aOR: Adjusted Odd Ratio, CI: Confidence Interval, DR: Diabetic Retinopathy.

Table 4: Determinants of heart failure incidence in diabetics