CONTEXT AND OBJECTIVES

L’hypertension artérielle (HTA) est le facteur de risque cardiovasculaire (FRCV) numéro un de par sa prévalence dans le monde.
D’aucuns considèrent l’HTA comme un état d’insulinorésistance (IR) étant donné la grande prévalence de l’IR parmi les hypertendus même non diabétiques et non obèses. Au cours de l’HTA, le cœur subit un remodelage ventriculaire gauche (RVG) modifiant sa taille, sa forme et sa fonction. L’hypertrophie ventriculaire gauche (HVG), un des phénotypes de ce remodelage, revêt une valeur pronostique péjorative quoique tous les hypertendus ne soient pas exposés au même risque
cardiovasculaire, ni à celui de RVG. L’IR figure parmi les facteurs identifiés pour expliquer cette différence. Les résultats des études sur l’association entre l’IR et le RVG ne sont pas concordants. L’influence de l’IR sur le RVG n’ayant pas encore été explorée en Afrique subsaharienne (ASS), ni son impact sur le pronostic vital associé à l’HVG dans le monde, la présente dissertation doctorale entend combler cette lacune.

METHODS

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

• une série consécutive clinique transversale analytique d’hypertendus suivis en ambulatoire à la Clinique Lomo Médical, à Kinshasa en République Démocratique du Congo (RDC), de janvier 2012 à janvier 2013. Elle a permis de déterminer la prévalence et d’identifier les déterminants de l’IR dans l’HTA essentielle;
• une étude populationnelle transversale-analytique a été menée dans la Ville de Marrakech, au Royaume du Maroc, de novembre 2015 à janvier 2016. Elle a permis de comparer la masse ventriculaire gauche (MVG) d’étudiants Noirs subsahariens vivant à Marrakech à celle d’étudiants Blancs Maghrébins de la même ville. Elle a également étudié l’influence
  lifestyle on MVG in these two specific populations;
• une étude monocentrique transversale analytique a inclus des hypertendus SUIVIS en ambulatoire au Centre Médical de Kinshasa (CMK), de janvier à décembre 2019. Elle a permis d’étudier l’effet de l’IR sur le RVG ainsi que l’association entre l’IR et l’HVG ;
• une étude hospitalière multicentrique transversale analytique, a inclus des hypertendus consécutivement sélectionnés lors des consultations ambulatoires dans 5 hôpitaux de Kinshasa, du mardi 24 septembre 2019, journée mondiale du cœur, au samedi 28 septembre 2019. Elle a permis d’étudier l’influence du régime alimentaire et des apports
  alimentaires en sodium sur l’IR d’une part et sur le RVG d’autre part;
• une étude également hospitalière multicentrique transversale analytique, a inclus des hypertendus consécutivement sélectionnés lors de consultations ambulatoires dans 5 hôpitaux de Kinshasa, du 1er octobre au 1er novembre 2019. Elle a permis d’étudier la valeur pronostique de l’HVG en utilisant la capacité cardiorespiratoire exprimée en
  V02max comme substitut du risque de mortalité globale. Elle a également étudié l’effet de l’IR sur l’association entre l’HVG et le risque de mortalité globale des hypertendus.

RESULTS

L’analyse des données des cinq études a montré ce qui suit:

1. one in two hypertensive patients was insulin resistant;
2. les déterminants de l’IR étaient d’ordre comportemental (le tabagisme par cigarette), alimentaire (la consommation de fruits et légumes et les apports journaliers de sel de cuisine), hémodynamique (le non contrôle de l’HT A) et biologique (hypertriglycéridémie et hyperuricémie);
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. l’IR multipliait par huit le risque d’HVG, l’obésité globale par trois;
6. l’IR semblait contribuer .à la majoration de la MVG en augmentant le diamètre télédiastolique (DTD), tandis que l’hyperinsulinémie semblait y contribuer en augmentant l’épaisseur de la PPd. Ensemble,· les deux anomalies agiraient sur le septum interventriculaire et contribueraient à la dysfonction diastolique en allongeant le TDE;
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. les participants avec HVG avaient un V02max plus bas et donc un risque de mortalité globale plus élevé que ceux sans HVG. Chez les participants avec IR, la MVG et le V02max étaient corrélés négativement. Chez les participants sans IR, la MVG et le V02max n’ont pas montré de corrélation significative. L’IMC et la MVG sont apparus comme des déterminants indépendants du V02max chez les participants insulinorésistants. Cette relation n’a pas été retrouvée chez les participants sans IR.

CONCLUSION

L’IR est présente chez la moitié des participants avec HTA essentielle. Comme l’HVG dont elle est un déterminant, l’IR est associée à un sur-risque de mortalité globale. Le risque de mortalité associé à l’HVG est fortement dépendant de l’état d’IR.

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 multicentre 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 remodelling.

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 sait 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.