CONTEXT AND OBJECTIVES

High blood pressure (HBP) is the number one cardiovascular risk factor (CVRF) in terms of its prevalence worldwide.
Some consider hypertension to be a state of insulin resistance (IR) given the high prevalence of IR among hypertensive patients, even those without diabetes and without obesity. During hypertension, the heart undergoes left ventricular remodeling (LVM), altering its size, shape, and function. Left ventricular hypertrophy (LVH), one of the phenotypes of this remodeling, has a poor prognostic value, although not all hypertensive patients are at the same risk.
cardiovascular, nor to that of RVG. IR is among the factors identified to explain this difference. The results of studies on the association between IR and RVG are not consistent. As the influence of IR on RVG has not yet been explored in sub-Saharan Africa (SSA), nor its impact on the vital prognosis associated with LVH worldwide, this doctoral dissertation aims to fill this gap.

METHODS

Five cross-sectional studies, including four in Kinshasa and one in Marrakech, were conducted to achieve this objective:

• a consecutive clinical cross-sectional analytical series of hypertensive patients followed as outpatients at the Lomo Médical Clinic, in Kinshasa in the Democratic Republic of Congo (DRC), from January 2012 to January 2013. It made it possible to determine the prevalence and identify the determinants of IR in essential hypertension;
• A cross-sectional population-analytic study was conducted in the city of Marrakech, Kingdom of Morocco, from November 2015 to January 2016. It compared the left ventricular mass (LVM) of Black sub-Saharan students living in Marrakech with that of White Maghrebi students from the same city. It also studied the influence
  lifestyle on MVG in these two specific populations;
• a single-center, cross-sectional, analytical study included hypertensive patients monitored as outpatients at the Kinshasa Medical Center (CMK), from January to December 2019. It made it possible to study the effect of IR on RVG as well as the association between IR and LVH;
• a multicenter, cross-sectional, analytical hospital study included consecutively selected hypertensive patients during outpatient consultations in 5 hospitals in Kinshasa, from Tuesday, September 24, 2019, World Heart Day, to Saturday, September 28, 2019. It made it possible to study the influence of diet and intake
  sodium dietary intake on the IR on the one hand and on the RVG on the other;
• a multicenter, cross-sectional, analytical hospital study, also included hypertensive patients consecutively selected during outpatient consultations in 5 hospitals in Kinshasa, from October 1 to November 1, 2019. It made it possible to study the prognostic value of LVH using cardiorespiratory capacity expressed in
  V02max as a surrogate for overall mortality risk. It also investigated the effect of IR on the association between LVH and overall mortality risk in hypertensive patients.

RESULTS

Analysis of data from the five studies showed the following:

1. one in two hypertensive patients was insulin resistant;
2. the determinants of IR were behavioral (cigarette smoking), dietary (consumption of fruits and vegetables and daily intake of table salt), hemodynamic (non-control of hypertension) and biological (hypertriglyceridemia and hyperuricemia);
3. insulin-resistant hypertensives had a higher frequency of CVRF;
4. MVG was similar between sub-Saharan Blacks and North African Whites. However, the posterior wall (PPd) was thicker in the sub-Saharan Black population;
5. IR increased the risk of LVH eightfold, overall obesity threefold;
6. IR appeared to contribute to the increase in LVD by increasing the end-diastolic diameter (EDD), while hyperinsulinemia appeared to contribute by increasing the thickness of the PPd. Together, the two abnormalities would act on the interventricular septum and contribute to diastolic dysfunction by lengthening the EDD;
7. Daily sodium intake and average weekly red meat intake were positively correlated with VGM. Fruit intake was positively correlated with EL, and negatively with VGM and TDE. Fish intake was negatively correlated with VGM. Vegetable intake had a negative correlation with TDE;
8. Fruit consumption, red meat consumption and salt consumption emerged as independent determinants of MVG explaining 53% of its variability;

9. Participants with LVH had a lower V02max and therefore a higher risk of overall mortality than those without LVH. In participants with IR, LVH and V02max were negatively correlated. In participants without IR, LVH and V02max did not show a significant correlation. BMI and LVH appeared to be independent determinants of V02max in insulin-resistant participants. This relationship was not found in participants without IR.

CONCLUSION

IR is present in half of participants with essential hypertension. Like LVH, of which it is a determinant, IR is associated with an excess risk of overall mortality. The mortality risk associated with LVH is highly dependent on IR status.

Keywords: Sub-Saharan Africa, dietetics, essential hypertension, left ventricular hypertrophy, insulin resistance, left ventricular remodeling, sedentary lifestyle, V02max.

BACKGROUND AND AIMS

Hypertension (HTN) is the number one cardiovascular risk factor (CVRF) in terms of its prevalence worldwide. Given the high prevalence of insulin resistance (IR) among hypertensive patients and the strong link between HTN and IR, HTN has been considered by some authors to be an insulin resistance condition. During hypertension, the heart undergoes left ventricular remodeling, which is a collection of changes in its size, shape and function.

Left ventricular hypertrophy (L VH), one of the phenotypes of this left ventricular remodeling, has po or prognostic value. It seems that not ail hypertensive patients are exposed to the same cardiovascular risk, nor to the same risk of left ventricular remodeling. IR is one of the factors identified to explain this difference. The results of various studies on the association between IR and left ventricular remodeling are not consistent.

To our knowledge, the influence of IR on left ventricular remodeling has not yet been studied in the Democratic Republic of Congo (DRC) in particular and in sub-Saharan Africa (SSA) in general. The influence of IR on L VH-related prognosis has not yet been studied in the DRC or anywhere else in the world. This thesis intends to fill this gap.

METHODS

Five cross-sectional studies, including four in Kinshasa and one in Marrakech, were carried out to achieve this objective:

1. A clinical cross-sectional analytical series was carried out on a sample of 163 cases of essential hypertension received in outpatient consultation at the Lomo-medical Clinic. It determined the prevalence and identified the determinants of IR in essential hypertension.

2. A descriptive analytical cross-sectional population-based study was carried out in the City of Marrakech, in the Kingdom of Morocco. It compared the left ventricular mass (LVM) of Black sub-Saharan students living in Marrakech to that of White Maghrebi students from the same city. This study also examined the influence of lifestyle (diet and sedentary behavior) on L VM in these two specified populations.

3. a descriptive analytical cross-sectional single-center study included hypertensive patients followed on an outpatient basis at the Center Médical de Kinshasa (CMK) from January to December 2019. It made it possible to study the effect of IR on left ventricular remodeling as weil as the association between IR and L VH.

4. A descriptive analytical cross-sectional multicenter hospital study included consecutively selected participants during outpatient consultations in 5 hospitals in Kinshasa, for 5 consecutive days during “Heart Week”, that is to say from Tuesday September 24, 2019, World Heart Day, until Saturday September 28,2019. It allowed us to study the influence of diet and dietary sodium intake on IR and on left ventricular remodeling.

5. Another descriptive analytical cross-sectional mu1ticentre hospital study included consecutively selected participants during outpatient consultations in 5 hospitals in Kinshasa, from October 1 to November 1, 2019. It made it possible to study the
prognostic value of LVH using cardiopulmonary capacity as a surrogate for overall mortality risk. This study also assessed the influence of IR on LVH-related overall mortality risk.

RESULTS

• Analysis of the data from the five studies showed the following:
• With the eut-off for IR defined as a homeostasis model assessment of IR (HOMA-IR) ≥ 2.5, the hospital prevalence of IR was 48.5%;
• Cigarette smoking, hypertriglyceridaemia, hyperuricaemia and uncontrolled hypertension appear to be independent determinants of IR, according to the single-center hospital study. Other determinants have been identified in a multicenter hospital study; they are total obesity and low consumption of fruits, vegetables and fish;
• Insulin-resistant hypertensive patients are at increased cardiovascular risk compared to non-insulin-resistant hypertensive patients. This is evidenced by a higher frequency of cardiovascular risk factors and lower cardiorespiratory capacity, expressed in V02 max (15.7 ± 5.5 ml/min/kg vs 18.4 ± 3.7 ml/min/kg; p = 0.001);
• LVM – crude or indexed by body surface area or by height 2. 7 – was similar between Black sub-Saharans and White. However, the posterior wall thickness (PWT) was greater in the Black sub-Saharans (8.3 ± 1.2 mm vs 7.9 ± 1.3 mm, p = 0.0 Il);
• ln multivariate analysis, 46.8% of the variation in the interventricular septum thickness (lVS; R2 = 0.468; global p overall 0.001) and 30.9% of the deceleration time of the E wave (DT; R2 = 0.309; global p = 0.003) were explained by insulin and HOMA-IR; 30.1% of the variation in left ventricular end-diastolic diameter (LVED; R2 = 0.301; P = 0.013)
  by HOMA-IR alone; and 46.3% of posterior wall thickness (PWT; R2 = 0.463; P = 0.002) and 29.4% of the relative wall thickness (RWT; R2 = 0.294; P = 0.007) by insulin alone;
• Daily sodium consumption was positively correlated with LVM and associated measurements (lVS, PWT, RWT). Red meat consumption was positively correlated with IVS, sum of wall thicknesses and LVM. Fruit consumption was positively correlated with the parameter of diastolic function and negatively correlated with L VED, LVM and DT.
  Fish consumption was negatively correlated with LVM. Vegetable consumption was negatively correlated with DT. ln multiple linear regression analysis, fruit consumption, red meat consumption and knows consumption emerged as independent determinants of LVM, L VM indexed to height (L VMlh) and LVM indexed to body surface area (LVMIbsa), respectively explaining 53%, 51 % and 52% of the parameters' variability;
• ln participants with IR, LVM (r = -0.261, P = 0.012), LVMlbsa (r = -0.229, P = 0.027) and L VMlh (1′ = -0.351, P = 0.001) were negatively correlated with V02 max. ln participants without IR, these same parameters did not correlate with V02 max.

CONCLUSION

IR is present in half of patients with essential hypertension. IR is a determinant of LVH. Both are associated with an increased risk of overall mortality and are linked to dietary factors and sedentary lifestyle. L VH related overall mortality risk is strongly dependent on the IR condition.

Keywords: Essential hypertension, diet, Insulin resistance, left ventricular hypertrophy, left ventricular remodeling, sedentary lifestyle, sub-Saharan Africa, V02 max.