- Email: [email protected]
Metabolic syndrome in hypertensive women
Topic 6 - Hypertension 331
Respective roles of genetic background and high fat diet in a rodent model of metabolic syndrome G. Hubesch ∗ , A. Hanthazi , A. Acheampong , C. Watu Malu , E. Hupkens , P. Jespers , G. Vegh , L. Dewachter , K. Mc Entee Laboratoire de physiologie et pharmacologie, ULB, Bruxelles, Belgique ∗ Corresponding author. E-mail address: [email protected] (G. Hubesch) Introduction The metabolic syndrome is a worldwide public health problem. Major cause is the junk food associated with a genetic predisposition. To better understand the mechanisms it is imperative to develop animal models closest to human problem. Objective Cardiometabolic alterations were studied in a polygenic rat model of metabolic syndrome. We therefore evaluated the respective roles of the substrain and the diet. Method Ten obese prone (OP), obese resistant (OR) and control (CTRL) Sprague—Dawley rats were fed with high fat (HF) or standard diet (SD) for 16 weeks. Feeding behaviour and criteria of the metabolic syndrome were determined. Arterial pressure was weekly recorded. Leptin and adiponectin were measured. Results CTRL and OR rats regulated their appetite to maintain a reasonable global calorie intake irrespective of the diet. OP rats showed higher food consumption and their calorie intake increased on HF. The mean abdominal fat % increase when on HF was higher in OP compared to CTRL and OR (236.1% vs. 89.97% and 65.99%). Total cholesterol and triglycerides were increased in OP-HF rats compared to the 5 other groups while OP showed a high nonHDL/HDL ratio already on SD. OP-HF rats had glucose intolerance. OP-HF rats showed an over time increase of systolic and diastolic arterial pressures and increased diastolic pressure at week 16 (117 ± 6 vs. 89 ± 6 and 93 ± 3 mmHg in OR-HF and CTRL-HF). Plasma leptin was increased in OP rats irrespective of the diet, suggesting a leptin resistance (4.8 ± 0.8 and 5.8 ± 0.5 ng/ml in OPSD and OP-HF). In accordance with their satiety, leptin increased in CTRL and OR fed with HF (2.95 ± 0.6 and 2.98 ± 0.7 ng/ml vs. 0.65 ± 0.1 and 1 ± 0.1 ng/ml in CTRL-SD and OR-SD). The leptin/adiponectin ratio was elevated in OP regardless of the diet. Conclusion The OP substrain is characterized by high plasma leptin and a loss of satiety leading to obesity and increased nonHDL/HDL ratio. When associated with HF, OP rats develop a metabolic syndrome. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.047 277
Role of Connexin 43 increased expression in pulmonary arterial hyperreactivity induced by the nerve growth factor NGF G. Cardouat 1,∗ , M. Douard 1 , P. Robillard 1 , M. Dubois 1 , R. Marthan 1,2 , B. Muller 1 , C. Guibert 1 , V. Freund-Michel 1 , Z. Kmecová 3 1 Centre de Recherche Cardio-Thoracique de Bordeaux, Inserm U1045 Université de Bordeaux, Pessac 2 CHU de Bordeaux, Bordeaux, France 3 Département de Pharmacologie et de Toxicologie, Université Comonius, Bratislava, Slovaquie ∗ Corresponding author. E-mail address: [email protected] (G. Cardouat) Introduction We have previously shown that the nerve growth factor (NGF) plays a critical role in pathophysiology of pulmonary
203 hypertension (PH) by promoting pulmonary arterial (PA) inflammation, remodelling and hyperreactivity. Aim To characterize mechanisms activated by NGF to induce PA hyperreactivity, focusing in particular on Connexin 43 (Cx43), a gap junction protein essential for vascular reactivity. Methods Cx43 expression was evaluated by Western blotting after NGF treatment (100 ng/ml, 24 h) ex vivo on rat pulmonary arteries or in vitro in primary human PA smooth muscle cells (hPASMC). Cx43 sub-cellular localization in hPASMC was evaluated by cell surface biotinylation and mitochondrial isolation. Contractions of control rat pulmonary arteries were induced ex vivo by phenylephrine (PHE, 10-10-10-4 M) in absence or presence of NGF (100 ng/ml, 24 h). The role of Cx43 in NGF-induced rat PA reactivity was evaluated ex vivo by use of 43Gap26 (Cx43 blocking peptide, 300 M), or in vivo by use of an anti-Cx43 siRNA (10nmol IV). Results NGF increases Cx43 total expression in rat pulmonary arteries and in hPASMC. This effect is totally abolished after treatment with K252a (TrkA kinase inhibitor), wortmannin (PI3 K inhibitor) or PD98059 (ERK pathway inhibitor). NGF-induced PA hyperreactivity to PHE is inhibited ex vivo by treatment with 43Gap26 or in vivo after administration of Cx43 siRNA. Subcellular localization experiments in hPASMC show, as expected, Cx43 increased expression by NGF at the plasma membrane, but surprisingly also in mitochondria. Conclusion These results show that NGF increases Cx43 PA expression through activation of its TrkA receptor and a PI3 K/ERKdependent signalling pathway. Cx43 increased expression at hPASMC plasma membrane seems to participate in NGF-induced PA hyperreactivity. The role of Cx43 increased mitochondrial expression by NGF in hPASMC needs to be further elucidated. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.048 186
Metabolic syndrome in hypertensive women M. Mouadili ∗ , C. Mbauchy , S. Elkarimi , M. Elhattaoui Cardiologie et maladies vasculaires, Centre hospitalier universitaire Mohammed VI Marrakech, Marrakech, Maroc ∗ Corresponding author. E-mail address: [email protected] (M. Mouadili) Background The metabolic syndrome (MetS) is recognized as a cluster of cardiovascular risk factors. Appropriate treatment can reduce cardiovascular morbidity and mortality. However, cardiologists may not routinely diagnosis the MetS. Aim To identify the prevalence of MetS among hypertensive women and to study the characteristics of this population. Methods We studied 248 hypertensive women, of median age 61(range: 18—86) years. Ten percent of them only were diagnosed as MetS. A health questionnaire was completed for all participants, including personal history of hypertension, diabetes mellitus (DM), smoking habits and medication. The waist circumference and blood pressure were measured as well as plasma glucose and the complete lipid profile. Results One hundred twenty two patients (49.19%) met the criteria for MetS. We divided our patients in three groups according their age (< 40, 40—65and > 65 years). There was no statistical significant difference in the prevalence of MetS in these 3 groups (50.7%, 43.6% and 53% respectively). Concerning MetS related factors; increased waist circumference was by far the most common one (86.88%). There was no significant difference in the prevalence of MetS between women with controlled or uncontrolled HTA. One hundred eight out of 248 females (43.54%) were diabetics, and the majority of them 92 (85.18%) met the criteria for MetS.
204
Topic 6 - Hypertension
Conclusion Our results suggest that the prevalence of MetS is dramatically increased among hypertensive women and this prevalence is not influenced by age. Interventions should be planned to increase the awareness of cardiologists to diagnose and treat the MetS. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.049 198
Hypertensive patients: Evaluation of a therapeutic education program M. Mouadili ∗ , C. Mbauchy , D. Benzaroual , S. Elkarimi , M. Elhattaoui Cardiologie et maladies vasculaires, Centre hospitalier universitaire Mohammed VI Marrakech, Marrakech, Maroc ∗ Corresponding author. E-mail address: [email protected] (M. Mouadili) Objective Evaluation of a therapeutic education program for hypertensive patients over a 6-month period with personalized objectives. Patients and methods A prospective single-center study conducted in 106 patients, the study was conducted as follows: — an initial collection of epidemiological, clinical and paraclinical data from patients in normal consultation; — each patient received a therapeutic education session personalized- with education in the use of the ‘‘hypertension follow-up notebooks’’ developed by the work team (Fig. 1); — the monitoring of the effectiveness of the education program was carried out over three evaluation consultations over the 6 months of the survey. Results One hundred and six patients participated in the study: mean age 47 ± 10 years; 62.26% of them were male (66 patients). Essential hypertension in 95.28% of patients, grade II to III, uncontrolled in approximately 70% of them. With an average evolution period of 9.5 ± 7.5 years. At 6 months, a significant decrease of SAP (from 154 ± 3 to 143 ± 3 mmHg, P less than 0.01) and DAP (from 95 ± 2 to 87 ± 2 mmHg, P less than 0.01) was notified. 50.7% versus 33.8% of patients have SAP and DAP in the therapeutic objectives. The monitoring of dietary and physical activity objectives is correlated with the decrease in BP (P < 0.05). A significant increase in self-monitoring with therapeutic decision-making (P < 0.01). A significant decrease in hypertension-related distress and feelings of failure (P < 0.01). Success rate among patients who chose the objective ‘‘reduce salt’’: 53%, ‘‘reduce fat’’: 50%, ‘‘walk several times/week (30 min)’’: 88%, ‘‘exercise at least once/week’’: 22%. 67% have at least one physical activity objective in place. No significant decrease in weight (−0.6 ± 4.1 kg) but 39% lost at least 2 kg. Conclusion A therapeutic education program with personalized objectives can give significant results at 6 months in terms of BP figures, dietetics and physical activity, self-monitoring of hypertension while reducing feelings of distress.
Fig. 1 Booklet of information and monitoring of hypertensive patients.
Disclosure of interest peting interest
The authors declare that they have no com-
https://doi.org/10.1016/j.acvdsp.2019.02.050 406
Specific treatment of pulmonary artery hypertension in Eisenmenger patients: About 4 cases H. Adnane ∗ , A. Eladaoui , O. Naour , A. Drighil , R. Habbal Cardiologie, CHU Ibn Rochd Casablanca, Casablanca, Maroc ∗ Corresponding author. E-mail address: [email protected] (H. Adnane) Introduction Eisenmenger’s syndrome is defined by the appearance of cyanosis during the evolution of left-right shunts, due to a progressive alteration of the pulmonary arteriolar bed, leading to an increase in pulmonary vascular resistance. This evolution of the shunt towards a reaction of Eisenmenger, makes that its simple surgical closure becomes useless. The only surgical treatment is pulmonary transplantation, or cardiopulmonary transplantation. The interest of specific medical treatment of pulmonary arterial hypertension in Eisenmenger Syndrome remains controversial. Objective Evaluate the impact of the specific treatment of PAH on Eisenmenger patients. Methods We report the evolution over 1 year of 4 patients with congenital heart diseases in Eisenmenger. For each patient we evaluated NYHA functional class, 6 MWT, echocardiographic and hemodynamic parameters. Results Two of our patients had atrioventricular canal defect: — one complete; — the other partial; 2 patients with patent arterial duct. These patients were put under specific treatment of PAH: sildenafil + macitentan. Clinically, there was a slight improvement in the dyspnoea stage from stage III to II, with an average of 6MWT at 287 m. On the echocardiographic plan Peak tricuspid regurgitation velocity which averaged 4.59 m/s decreased to 3.5 m/s after one year of treatment with PASP by tricuspid regurgitation on average at 93 mmHg at the beginning of the treatment then at 70 mmHg at 1 year. Humodynamically, the PAPm (mmHg) were at 38 before specific treatment and decreased to 32 at the end of treatment, with a cardiac output that went from 2.3 to 2.5 l/min/m2 , and an RVP of 7 to 5 wood units. We did not notice any complications and no deaths were reported.
Respective roles of genetic background and high fat diet in a rodent model of metabolic syndrome G. Hubesch ∗ , A. Hanthazi , A. Acheampong , C. Watu Malu , E. Hupkens , P. Jespers , G. Vegh , L. Dewachter , K. Mc Entee Laboratoire de physiologie et pharmacologie, ULB, Bruxelles, Belgique ∗ Corresponding author. E-mail address: [email protected] (G. Hubesch) Introduction The metabolic syndrome is a worldwide public health problem. Major cause is the junk food associated with a genetic predisposition. To better understand the mechanisms it is imperative to develop animal models closest to human problem. Objective Cardiometabolic alterations were studied in a polygenic rat model of metabolic syndrome. We therefore evaluated the respective roles of the substrain and the diet. Method Ten obese prone (OP), obese resistant (OR) and control (CTRL) Sprague—Dawley rats were fed with high fat (HF) or standard diet (SD) for 16 weeks. Feeding behaviour and criteria of the metabolic syndrome were determined. Arterial pressure was weekly recorded. Leptin and adiponectin were measured. Results CTRL and OR rats regulated their appetite to maintain a reasonable global calorie intake irrespective of the diet. OP rats showed higher food consumption and their calorie intake increased on HF. The mean abdominal fat % increase when on HF was higher in OP compared to CTRL and OR (236.1% vs. 89.97% and 65.99%). Total cholesterol and triglycerides were increased in OP-HF rats compared to the 5 other groups while OP showed a high nonHDL/HDL ratio already on SD. OP-HF rats had glucose intolerance. OP-HF rats showed an over time increase of systolic and diastolic arterial pressures and increased diastolic pressure at week 16 (117 ± 6 vs. 89 ± 6 and 93 ± 3 mmHg in OR-HF and CTRL-HF). Plasma leptin was increased in OP rats irrespective of the diet, suggesting a leptin resistance (4.8 ± 0.8 and 5.8 ± 0.5 ng/ml in OPSD and OP-HF). In accordance with their satiety, leptin increased in CTRL and OR fed with HF (2.95 ± 0.6 and 2.98 ± 0.7 ng/ml vs. 0.65 ± 0.1 and 1 ± 0.1 ng/ml in CTRL-SD and OR-SD). The leptin/adiponectin ratio was elevated in OP regardless of the diet. Conclusion The OP substrain is characterized by high plasma leptin and a loss of satiety leading to obesity and increased nonHDL/HDL ratio. When associated with HF, OP rats develop a metabolic syndrome. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.047 277
Role of Connexin 43 increased expression in pulmonary arterial hyperreactivity induced by the nerve growth factor NGF G. Cardouat 1,∗ , M. Douard 1 , P. Robillard 1 , M. Dubois 1 , R. Marthan 1,2 , B. Muller 1 , C. Guibert 1 , V. Freund-Michel 1 , Z. Kmecová 3 1 Centre de Recherche Cardio-Thoracique de Bordeaux, Inserm U1045 Université de Bordeaux, Pessac 2 CHU de Bordeaux, Bordeaux, France 3 Département de Pharmacologie et de Toxicologie, Université Comonius, Bratislava, Slovaquie ∗ Corresponding author. E-mail address: [email protected] (G. Cardouat) Introduction We have previously shown that the nerve growth factor (NGF) plays a critical role in pathophysiology of pulmonary
203 hypertension (PH) by promoting pulmonary arterial (PA) inflammation, remodelling and hyperreactivity. Aim To characterize mechanisms activated by NGF to induce PA hyperreactivity, focusing in particular on Connexin 43 (Cx43), a gap junction protein essential for vascular reactivity. Methods Cx43 expression was evaluated by Western blotting after NGF treatment (100 ng/ml, 24 h) ex vivo on rat pulmonary arteries or in vitro in primary human PA smooth muscle cells (hPASMC). Cx43 sub-cellular localization in hPASMC was evaluated by cell surface biotinylation and mitochondrial isolation. Contractions of control rat pulmonary arteries were induced ex vivo by phenylephrine (PHE, 10-10-10-4 M) in absence or presence of NGF (100 ng/ml, 24 h). The role of Cx43 in NGF-induced rat PA reactivity was evaluated ex vivo by use of 43Gap26 (Cx43 blocking peptide, 300 M), or in vivo by use of an anti-Cx43 siRNA (10nmol IV). Results NGF increases Cx43 total expression in rat pulmonary arteries and in hPASMC. This effect is totally abolished after treatment with K252a (TrkA kinase inhibitor), wortmannin (PI3 K inhibitor) or PD98059 (ERK pathway inhibitor). NGF-induced PA hyperreactivity to PHE is inhibited ex vivo by treatment with 43Gap26 or in vivo after administration of Cx43 siRNA. Subcellular localization experiments in hPASMC show, as expected, Cx43 increased expression by NGF at the plasma membrane, but surprisingly also in mitochondria. Conclusion These results show that NGF increases Cx43 PA expression through activation of its TrkA receptor and a PI3 K/ERKdependent signalling pathway. Cx43 increased expression at hPASMC plasma membrane seems to participate in NGF-induced PA hyperreactivity. The role of Cx43 increased mitochondrial expression by NGF in hPASMC needs to be further elucidated. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.048 186
Metabolic syndrome in hypertensive women M. Mouadili ∗ , C. Mbauchy , S. Elkarimi , M. Elhattaoui Cardiologie et maladies vasculaires, Centre hospitalier universitaire Mohammed VI Marrakech, Marrakech, Maroc ∗ Corresponding author. E-mail address: [email protected] (M. Mouadili) Background The metabolic syndrome (MetS) is recognized as a cluster of cardiovascular risk factors. Appropriate treatment can reduce cardiovascular morbidity and mortality. However, cardiologists may not routinely diagnosis the MetS. Aim To identify the prevalence of MetS among hypertensive women and to study the characteristics of this population. Methods We studied 248 hypertensive women, of median age 61(range: 18—86) years. Ten percent of them only were diagnosed as MetS. A health questionnaire was completed for all participants, including personal history of hypertension, diabetes mellitus (DM), smoking habits and medication. The waist circumference and blood pressure were measured as well as plasma glucose and the complete lipid profile. Results One hundred twenty two patients (49.19%) met the criteria for MetS. We divided our patients in three groups according their age (< 40, 40—65and > 65 years). There was no statistical significant difference in the prevalence of MetS in these 3 groups (50.7%, 43.6% and 53% respectively). Concerning MetS related factors; increased waist circumference was by far the most common one (86.88%). There was no significant difference in the prevalence of MetS between women with controlled or uncontrolled HTA. One hundred eight out of 248 females (43.54%) were diabetics, and the majority of them 92 (85.18%) met the criteria for MetS.
204
Topic 6 - Hypertension
Conclusion Our results suggest that the prevalence of MetS is dramatically increased among hypertensive women and this prevalence is not influenced by age. Interventions should be planned to increase the awareness of cardiologists to diagnose and treat the MetS. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.049 198
Hypertensive patients: Evaluation of a therapeutic education program M. Mouadili ∗ , C. Mbauchy , D. Benzaroual , S. Elkarimi , M. Elhattaoui Cardiologie et maladies vasculaires, Centre hospitalier universitaire Mohammed VI Marrakech, Marrakech, Maroc ∗ Corresponding author. E-mail address: [email protected] (M. Mouadili) Objective Evaluation of a therapeutic education program for hypertensive patients over a 6-month period with personalized objectives. Patients and methods A prospective single-center study conducted in 106 patients, the study was conducted as follows: — an initial collection of epidemiological, clinical and paraclinical data from patients in normal consultation; — each patient received a therapeutic education session personalized- with education in the use of the ‘‘hypertension follow-up notebooks’’ developed by the work team (Fig. 1); — the monitoring of the effectiveness of the education program was carried out over three evaluation consultations over the 6 months of the survey. Results One hundred and six patients participated in the study: mean age 47 ± 10 years; 62.26% of them were male (66 patients). Essential hypertension in 95.28% of patients, grade II to III, uncontrolled in approximately 70% of them. With an average evolution period of 9.5 ± 7.5 years. At 6 months, a significant decrease of SAP (from 154 ± 3 to 143 ± 3 mmHg, P less than 0.01) and DAP (from 95 ± 2 to 87 ± 2 mmHg, P less than 0.01) was notified. 50.7% versus 33.8% of patients have SAP and DAP in the therapeutic objectives. The monitoring of dietary and physical activity objectives is correlated with the decrease in BP (P < 0.05). A significant increase in self-monitoring with therapeutic decision-making (P < 0.01). A significant decrease in hypertension-related distress and feelings of failure (P < 0.01). Success rate among patients who chose the objective ‘‘reduce salt’’: 53%, ‘‘reduce fat’’: 50%, ‘‘walk several times/week (30 min)’’: 88%, ‘‘exercise at least once/week’’: 22%. 67% have at least one physical activity objective in place. No significant decrease in weight (−0.6 ± 4.1 kg) but 39% lost at least 2 kg. Conclusion A therapeutic education program with personalized objectives can give significant results at 6 months in terms of BP figures, dietetics and physical activity, self-monitoring of hypertension while reducing feelings of distress.
Fig. 1 Booklet of information and monitoring of hypertensive patients.
Disclosure of interest peting interest
The authors declare that they have no com-
https://doi.org/10.1016/j.acvdsp.2019.02.050 406
Specific treatment of pulmonary artery hypertension in Eisenmenger patients: About 4 cases H. Adnane ∗ , A. Eladaoui , O. Naour , A. Drighil , R. Habbal Cardiologie, CHU Ibn Rochd Casablanca, Casablanca, Maroc ∗ Corresponding author. E-mail address: [email protected] (H. Adnane) Introduction Eisenmenger’s syndrome is defined by the appearance of cyanosis during the evolution of left-right shunts, due to a progressive alteration of the pulmonary arteriolar bed, leading to an increase in pulmonary vascular resistance. This evolution of the shunt towards a reaction of Eisenmenger, makes that its simple surgical closure becomes useless. The only surgical treatment is pulmonary transplantation, or cardiopulmonary transplantation. The interest of specific medical treatment of pulmonary arterial hypertension in Eisenmenger Syndrome remains controversial. Objective Evaluate the impact of the specific treatment of PAH on Eisenmenger patients. Methods We report the evolution over 1 year of 4 patients with congenital heart diseases in Eisenmenger. For each patient we evaluated NYHA functional class, 6 MWT, echocardiographic and hemodynamic parameters. Results Two of our patients had atrioventricular canal defect: — one complete; — the other partial; 2 patients with patent arterial duct. These patients were put under specific treatment of PAH: sildenafil + macitentan. Clinically, there was a slight improvement in the dyspnoea stage from stage III to II, with an average of 6MWT at 287 m. On the echocardiographic plan Peak tricuspid regurgitation velocity which averaged 4.59 m/s decreased to 3.5 m/s after one year of treatment with PASP by tricuspid regurgitation on average at 93 mmHg at the beginning of the treatment then at 70 mmHg at 1 year. Humodynamically, the PAPm (mmHg) were at 38 before specific treatment and decreased to 32 at the end of treatment, with a cardiac output that went from 2.3 to 2.5 l/min/m2 , and an RVP of 7 to 5 wood units. We did not notice any complications and no deaths were reported.