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1.
J Hum Hypertens ; 34(2): 108-116, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30568290

RESUMO

Aortic pulse wave velocity has emerged as an important predictor of cardiovascular events, but data on ethnic differences in pulse wave velocity remain scarce. We explored differences in pulse wave velocity between people of Asian and African ancestry. Data were used from the cross-sectional Healthy Life in Suriname (HELISUR) study. Pulse wave velocity was estimated oscillometrically with the Arteriograph. We included 353 Asians and 364 Africans, aged respectively 44.9 (SD 13.5) and 42.8 (SD 14.1) years (p = 0.05). Crude median PWV was higher in Asians than in Africans (8.1 [IQR 6.9-10.1] m/s vs. 7.7 [IQR 6.5-9.3] m/s, p = 0.03), which was mainly attributable to an increased PWV in Asians ≥ 50 years (10.1 [IQR 8.7-11.8] m/s vs. 9.1 [IQR 7.9-11.3] m/s in Africans ≥50 years, p < 0.01). After adjustment for age and MAP in multivariable linear regression, Asians had a 1.044 [95% CI 1.019-1.072] m/s higher PWV compared to Africans. Additional adjustment for sex, glucose, total cholesterol, HDL cholesterol, triglycerides, BMI, and waist circumference did not substantially change the difference in pulse wave velocity between Asians and Africans (+1.044 [95% CI 1.016-1.074] m/s for Asians vs. Africans). In conclusion, persons of Asian ancestry have a higher pulse wave velocity than those of African ancestry. This persisted after adjustment for important cardiovascular risk parameters, including age and blood pressure. The higher PWV found in Asians could be consistent with their increased coronary heart disease risk.


Assuntos
Povo Asiático , Análise de Onda de Pulso , Idoso , Estudos Transversais , Humanos , Fatores de Risco , Suriname
2.
J Clin Hypertens (Greenwich) ; 20(2): 334-341, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29357199

RESUMO

Creatine kinase (CK) rapidly regenerates ATP for Na+ /K+ -ATPase driven sodium retention throughout the kidney. Therefore, we assessed whether resting plasma CK is associated with sodium retention after a high sodium diet. Sixty healthy men (29 European and 31 African ancestry) with a mean age of 37.2 years (SE 1.2) were assigned to low sodium intake (< 50 mmol/d) during 7 days, followed by 3 days of high sodium intake (> 200 mmol/d). Sodium excretion (mmol/24-h) after high sodium was 260.4 (28.3) in the high CK tertile versus 415.2 (26.3) mmol/24-h in the low CK tertile (P < .001), with a decrease in urinary sodium excretion of 98.4 mmol/24-h for each increase in log CK, adjusted for age and African ancestry. These preliminary results are in line with the energy buffering function of the CK system, but more direct assessments of kidney CK will be needed to further establish whether this enzyme enhances sodium sensitivity.


Assuntos
Creatina Quinase/sangue , Hipertensão , Eliminação Renal/fisiologia , Sódio na Dieta , Adulto , População Negra , Determinação da Pressão Arterial/métodos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/etnologia , Hipertensão/fisiopatologia , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Sódio na Dieta/sangue , Sódio na Dieta/metabolismo , População Branca
3.
Am J Hypertens ; 30(11): 1133-1140, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28985247

RESUMO

BACKGROUND: Hypertension is the leading risk factor responsible for premature death worldwide, but its burden has shifted to low- and middle-income countries. Therefore, we studied hypertension and cardiovascular risk in the population of Suriname, a middle-income country with a predominantly urban population of African and Asian ancestry. METHODS: A random sample of 1,800 noninstitutionalized men and women aged 18-70 years was selected to be interviewed at home and examined at the local hospital for cardiovascular risk factors, asymptomatic organ damage, and cardiovascular disease. RESULTS: The 1,157 participants examined (37% men) were mainly of self-defined Asian (43%) or African (39%) ancestry, mean age 43 years (SD 14). The majority of the population (71%) had hypertension or prehypertension, respectively, 40% and 31%. Furthermore, 72% was obese or overweight, while 63% had diabetes or prediabetes. Only 1% of the adult population had an optimal cardiovascular risk profile. Hypertension awareness, treatment, and control were respectively 68%, 56%, and 20%. In line with this, 22% of the adult population had asymptomatic organ damage, including increased arterial stiffness, left ventricular hypertrophy, microalbuminuria, or asymptomatic chronic kidney disease. CONCLUSIONS: In this first extensive cardiovascular assessment in the general population of this middle-income Caribbean country, high prevalence of hypertension with inadequate levels of treatment and control was predominant. The findings emphasize the need for collaborative effort from national and international bodies to prioritize the implementation of affordable and sustainable public health programs that combat the escalating hypertension and cardiovascular risk factor burden.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Hipertensão/epidemiologia , Fatores Socioeconômicos , Adolescente , Adulto , Idoso , Povo Asiático , População Negra , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Causas de Morte , Comorbidade , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Suriname/epidemiologia , Adulto Jovem
4.
Br J Clin Pharmacol ; 83(12): 2626-2635, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28795416

RESUMO

AIMS: Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure-lowering agent, we assessed the tolerability of a sub-therapeutic GPA dose in healthy men. METHODS: In this active and placebo-controlled, triple-blind, single-centre trial, we recruited 24 healthy men (18-50 years old, BMI 18.5-29.9 kg m-2 ) in the Netherlands. Participants were randomized (1:1:1) to one week daily oral administration of GPA 100 mg, creatine 5 g, or matching placebo. The primary outcome was the tolerability of GPA, in an intent-to-treat analysis. RESULTS: Twenty-four randomized participants received the allocated intervention and 23 completed the study. One participant in the placebo arm dropped out for personal reasons. GPA was well tolerated, without serious or severe adverse events. No abnormalities were reported with GPA use in clinical safety parameters, including physical examination, laboratory studies, or 12-Lead ECG. At day 8, mean plasma GPA was 213.88 (SE 0.07) in the GPA arm vs. 32.75 (0.00) nmol l-1 in the placebo arm, a mean difference of 181.13 (95% CI 26.53-335.72). CONCLUSION: In this first-in-human trial, low-dose GPA was safe and well-tolerated when used during 1 week in healthy men. Subsequent studies should focus on human pharmacokinetic and pharmacodynamic assessments with different doses.


Assuntos
Anti-Hipertensivos/administração & dosagem , Creatina/administração & dosagem , Guanidinas/administração & dosagem , Propionatos/administração & dosagem , Administração Oral , Adolescente , Adulto , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/sangue , Creatina/efeitos adversos , Esquema de Medicação , Guanidinas/efeitos adversos , Guanidinas/sangue , Voluntários Saudáveis , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Países Baixos , Propionatos/efeitos adversos , Propionatos/sangue , Resultado do Tratamento , Adulto Jovem
5.
Rev Panam Salud Publica ; 41: e46, 2017 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-28614469

RESUMO

OBJECTIVES: To determine the feasibility of assessing population cardiovascular risk with advanced hemodynamics in the Healthy Life in Suriname (HELISUR) study. METHODS: This was a preliminary study conducted in May - June 2012 using the Technical-Economic-Legal-Operational-Scheduling (TELOS) method to assess the feasibility of the HELISUR-a large-scale, cross-sectional population study of cardiovascular risk factors and disease in Suriname. Suriname, a middle-income country in South America with a population of mostly African and Asian ethnicity, has a high risk of cardiovascular disease. A total of 135 volunteers 18 - 70 years of age participated. A health questionnaire was tested in a primary health care center, and non-invasive cardiovascular evaluations were performed in an academic health center. The cardiovascular evaluation included sitting, supine, and standing blood pressure, and intermediate endpoints, such as cardiac output, peripheral vascular resistance, pulse wave velocity, and augmentation index. RESULTS: The TELOS testing found that communicating by cellular phone was most effective for appointment adherence, and that completion of the questionnaire often required assistance from a trained interviewer; modifications to improve the clarity of the questions are recommended. Regarding the extended cardiovascular assessments of peripheral and central hemodynamics, the findings showed these to be technically and operationally feasible and well tolerated by participants, in terms of burden and duration. CONCLUSIONS: Findings of this feasibility assessment indicate that large-scale, detailed evaluations of cardiovascular risk, including a questionnaire and advanced central and peripheral hemodynamics, are feasible in a high-risk population in a middle-income setting.


Assuntos
Doenças Cardiovasculares/diagnóstico , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Estudos de Viabilidade , Feminino , Testes de Função Cardíaca/métodos , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Suriname , Adulto Jovem
6.
Artigo em Inglês | PAHO-IRIS | ID: phr-34000

RESUMO

Objectives. To determine the feasibility of assessing population cardiovascular risk with advanced hemodynamics in the Healthy Life in Suriname (HELISUR) study. Methods. This was a preliminary study conducted in May – June 2012 using the Technical-Economic-Legal-Operational-Scheduling (TELOS) method to assess the feasibility of the HELISUR—a large-scale, cross-sectional population study of cardiovascular risk factors and disease in Suriname. Suriname, a middle-income country in South America with a population of mostly African and Asian ethnicity, has a high risk of cardiovascular disease. A total of 135 volunteers 18 – 70 years of age participated. A health questionnaire was tested in a primary health care center, and non-invasive cardiovascular evaluations were performed in an academic health center. The cardiovascular evaluation included sitting, supine, and standing blood pressure, and intermediate endpoints, such as cardiac output, peripheral vascular resistance, pulse wave velocity, and augmentation index. Results. The TELOS testing found that communicating by cellular phone was most effective for appointment adherence, and that completion of the questionnaire often required assistance from a trained interviewer; modifications to improve the clarity of the questions are recommended. Regarding the extended cardiovascular assessments of peripheral and central hemodynamics, the findings showed these to be technically and operationally feasible and well tolerated by participants, in terms of burden and duration. Conclusions. Findings of this feasibility assessment indicate that large-scale, detailed evaluations of cardiovascular risk, including a questionnaire and advanced central and peripheral hemodynamics, are feasible in a high-risk population in a middle-income setting.


Objetivos. Determinar la factibilidad de evaluar el riesgo de enfermedades cardiovasculares en la población utilizando hemodinámica avanzada en el estudio Vida Sana en Suriname (HELISUR por su sigla en inglés). Métodos. Este fue un estudio preliminar realizado de mayo a junio del 2012 empleando el método de factibilidad técnica, económica, legal, operativa y de programación (TELOS) para evaluar la factibilidad del HELISUR, un estudio poblacional transversal a gran escala de factores de riesgo y enfermedades cardiovasculares en Suriname. Suriname, un país de ingresos medianos de América del Sur, con una población de etnicidad principalmente africana y asiática, presenta un riesgo alto de enfermedades cardiovasculares. En el estudio participó un total de 135 voluntarios de 18 a 70 años de edad. Se puso a prueba un cuestionario de salud en un centro de atención primaria de salud, y se realizaron evaluaciones cardiovasculares no invasoras en un centro de salud académico. La evaluación cardiovascular incluyó mediciones de presión arterial en posición sentada, supina y de pie, y los criterios de valoración intermedios, como el gasto cardíaco, la resistencia vascular periférica, la velocidad de la onda de pulso y el índice de aumento. Resultados. En las pruebas del método TELOS se encontró que la comunicación por teléfono celular era la más eficaz para asegurar la asistencia a las citas y que a menudo se requería la presencia de un entrevistador capacitado para ayudar a los voluntarios a llenar el cuestionario; se recomienda modificar las preguntas para que sean más claras. Con respecto a las evaluaciones cardiovasculares prolongadas de hemodinámica periférica y central, los resultados demostraron que eran técnica y operativamente factibles, y bien toleradas por los participantes en cuanto a la carga y duración. Conclusiones. Los resultados de esta evaluación de factibilidad indican que las evaluaciones detalladas y a gran escala del riesgo de enfermedades cardiovasculares, que incluyen un cuestionario y hemodinámica central y periférica avanzada, son factibles para una población de alto riesgo en un país de ingresos medianos.


Objetivos. Determinar a viabilidade de avaliar o risco cardiovascular da população por meio de avaliação hemodinâmica avançada no Estudo de Vida Saudável no Suriname (HELISUR). Métodos. Estudo preliminar realizado em maio-junho de 2012 com o uso da metodologia TELOS (análise técnica, financeira, jurídica, operacional e do cronograma) para avaliar a viabilidade do HELISUR – estudo transversal de base populacional em grande escala dos fatores de risco e doenças cardiovasculares no Suriname. O Suriname é um país sul-americano de renda média de população majoritariamente de origem afro-asiática com alto risco da doença cardiovascular. Participaram do estudo 135 voluntários com 18 a 70 anos de idade. O questionário sobre saúde foi testado em uma unidade básica de saúde e avaliações cardiovasculares não invasivas foram realizadas em um centro de saúde acadêmico. A avaliação cardiovascular consistiu da medida da pressão arterial em posição sentada, supino e em pé, e da medida de parâmetros (endpoints) intermediários como débito cardíaco, resistência vascular periférica, velocidade da onda de pulso e índice de amplificação. Resultados. A análise TELOS indicou maior eficiência na adesão às consultas com a comunicação por celular e a necessidade frequente de auxílio de um entrevistador treinado para o preenchimento do questionário. Modificações para melhorar a compreensão das perguntas são recomendadas. Também se demonstrou que o amplo estudo da hemodinâmica central e periférica é viável do ponto de vista técnico e operacional e que os participantes toleram bem o incômodo e o tempo de avaliação. Conclusões. Os resultados da avaliação de viabilidade indicam que a avaliação aprofundada do risco cardiovascular em grande escala, incluindo a administração de questionário e estudos de hemodinâmica avançada central e periférica, é viável em uma população de renda média com alto risco.


Assuntos
Estudos de Viabilidade , Hemodinâmica , Técnicas de Diagnóstico Cardiovascular , Suriname , Estudos de Viabilidade , Hemodinâmica , Técnicas de Diagnóstico Cardiovascular , Saúde das Minorias Étnicas , Saúde das Minorias Étnicas
7.
Mol Cell Endocrinol ; 442: 24-31, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-27894867

RESUMO

OBJECTIVE: Creatine kinase (CK), the central regulatory enzyme of energy metabolism, is particularly high in type II skeletal muscle fibers, which are associated with insulin resistance and obesity. As resting plasma CK is mainly derived from skeletal muscle, we assessed whether plasma CK is associated with markers of obesity. METHODS: In this cross-sectional study, we analyzed a random sample of the multi-ethnic population of Amsterdam, the Netherlands, consisting of 1444 subjects aged 34-60 years. The primary outcome was the independent association between plasma CK after rest and waist circumference. Other outcomes included waist-to-hip ratio and body mass index. RESULTS: Mean waist circumference increased from the first through the third CK tertile, respectively 90.3 (SD 13.4), 93.2 (SD 14.3), and 94.4 (SD 13.3) cm (p < 0.001 for differences between tertiles). The increase in waist circumference was 8.91 (95% CI 5.35 to 12.47) cm per log CK increase after adjustment for age, sex, African ethnicity, educational level, physical activity and plasma creatinine. Similarly, CK was independently associated with waist-to-hip ratio and body mass index, with an increase of respectively 0.05 (95% CI 0.03 to 0.07) and 3.6 (95% CI 2.3 to 5.0) kg/m2 per log CK increase. CONCLUSIONS: Plasma CK is independently associated with measures of obesity in a multi-ethnic population. This is in line with the central role of type II skeletal muscle fibers in energy metabolism and obesity. Prospective studies should assess whether resting plasma CK could be an easy accessible marker of CK rich type II fiber predominance that helps identify individuals at risk for obesity.


Assuntos
Biomarcadores/sangue , Creatina Quinase/sangue , Obesidade/sangue , Adulto , Índice de Massa Corporal , Estudos Transversais , Metabolismo Energético/fisiologia , Etnicidade , Exercício Físico/fisiologia , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura/fisiologia , Relação Cintura-Quadril/métodos
8.
Rev. panam. salud pública ; 41: e46, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-845701

RESUMO

ABSTRACT Objectives To determine the feasibility of assessing population cardiovascular risk with advanced hemodynamics in the Healthy Life in Suriname (HELISUR) study. Methods This was a preliminary study conducted in May – June 2012 using the Technical-Economic-Legal-Operational-Scheduling (TELOS) method to assess the feasibility of the HELISUR—a large-scale, cross-sectional population study of cardiovascular risk factors and disease in Suriname. Suriname, a middle-income country in South America with a population of mostly African and Asian ethnicity, has a high risk of cardiovascular disease. A total of 135 volunteers 18 – 70 years of age participated. A health questionnaire was tested in a primary health care center, and non-invasive cardiovascular evaluations were performed in an academic health center. The cardiovascular evaluation included sitting, supine, and standing blood pressure, and intermediate endpoints, such as cardiac output, peripheral vascular resistance, pulse wave velocity, and augmentation index. Results The TELOS testing found that communicating by cellular phone was most effective for appointment adherence, and that completion of the questionnaire often required assistance from a trained interviewer; modifications to improve the clarity of the questions are recommended. Regarding the extended cardiovascular assessments of peripheral and central hemodynamics, the findings showed these to be technically and operationally feasible and well tolerated by participants, in terms of burden and duration. Conclusions Findings of this feasibility assessment indicate that large-scale, detailed evaluations of cardiovascular risk, including a questionnaire and advanced central and peripheral hemodynamics, are feasible in a high-risk population in a middle-income setting.


RESUMEN Objetivos Determinar la factibilidad de evaluar el riesgo de enfermedades cardiovasculares en la población utilizando hemodinámica avanzada en el estudio Vida Sana en Suriname (HELISUR por su sigla en inglés). Métodos Este fue un estudio preliminar realizado de mayo a junio del 2012 empleando el método de factibilidad técnica, económica, legal, operativa y de programación (TELOS) para evaluar la factibilidad del HELISUR, un estudio poblacional transversal a gran escala de factores de riesgo y enfermedades cardiovasculares en Suriname. Suriname, un país de ingresos medianos de América del Sur, con una población de etnicidad principalmente africana y asiática, presenta un riesgo alto de enfermedades cardiovasculares. En el estudio participó un total de 135 voluntarios de 18 a 70 años de edad. Se puso a prueba un cuestionario de salud en un centro de atención primaria de salud, y se realizaron evaluaciones cardiovasculares no invasoras en un centro de salud académico. La evaluación cardiovascular incluyó mediciones de presión arterial en posición sentada, supina y de pie, y los criterios de valoración intermedios, como el gasto cardíaco, la resistencia vascular periférica, la velocidad de la onda de pulso y el índice de aumento. Resultados En las pruebas del método TELOS se encontró que la comunicación por teléfono celular era la más eficaz para asegurar la asistencia a las citas y que a menudo se requería la presencia de un entrevistador capacitado para ayudar a los voluntarios a llenar el cuestionario; se recomienda modificar las preguntas para que sean más claras. Con respecto a las evaluaciones cardiovasculares prolongadas de hemodinámica periférica y central, los resultados demostraron que eran técnica y operativamente factibles, y bien toleradas por los participantes en cuanto a la carga y duración. Conclusiones Los resultados de esta evaluación de factibilidad indican que las evaluaciones detalladas y a gran escala del riesgo de enfermedades cardiovasculares, que incluyen un cuestionario y hemodinámica central y periférica avanzada, son factibles para una población de alto riesgo en un país de ingresos medianos.


RESUMO Objetivos Determinar a viabilidade de avaliar o risco cardiovascular da população por meio de avaliação hemodinâmica avançada no Estudo de Vida Saudável no Suriname (HELISUR). Métodos Estudo preliminar realizado em maio-junho de 2012 com o uso da metodologia TELOS (análise técnica, financeira, jurídica, operacional e do cronograma) para avaliar a viabilidade do HELISUR – estudo transversal de base populacional em grande escala dos fatores de risco e doenças cardiovasculares no Suriname. O Suriname é um país sul-americano de renda média de população majoritariamente de origem afro-asiática com alto risco da doença cardiovascular. Participaram do estudo 135 voluntários com 18 a 70 anos de idade. O questionário sobre saúde foi testado em uma unidade básica de saúde e avaliações cardiovasculares não invasivas foram realizadas em um centro de saúde acadêmico. A avaliação cardiovascular consistiu da medida da pressão arterial em posição sentada, supino e em pé, e da medida de parâmetros (endpoints) intermediários como débito cardíaco, resistência vascular periférica, velocidade da onda de pulso e índice de amplificação. Resultados A análise TELOS indicou maior eficiência na adesão às consultas com a comunicação por celular e a necessidade frequente de auxílio de um entrevistador treinado para o preenchimento do questionário. Modificações para melhorar a compreensão das perguntas são recomendadas. Também se demonstrou que o amplo estudo da hemodinâmica central e periférica é viável do ponto de vista técnico e operacional e que os participantes toleram bem o incômodo e o tempo de avaliação. Conclusões Os resultados da avaliação de viabilidade indicam que a avaliação aprofundada do risco cardiovascular em grande escala, incluindo a administração de questionário e estudos de hemodinâmica avançada central e periférica, é viável em uma população de renda média com alto risco.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Estudos de Viabilidade , Suriname
9.
J Hypertens ; 34(12): 2418-2426, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27512977

RESUMO

OBJECTIVE: Creatine kinase is reported to be a main predictor of blood pressure (BP) in the general population, with a strong correlation between resistance artery creatine kinase expression and clinical BP in humans. The enzyme rapidly regenerates ATP near cytoplasmic ATPases involved in pressor responses, including resistance artery contractility and renal sodium retention. Therefore, we assessed whether creatine kinase inhibition reduces BP. METHODS: We implemented the 'Animal Research: Reporting of In Vivo Experiments' guideline. In a 4-week randomized controlled trial, male 16-week-old spontaneously hypertensive rats (N = 16) were randomly assigned to the specific competitive creatine kinase inhibitor beta-guanidinopropionic acid (3%)-supplemented chow vs. standard chow. BP measured by the tail-cuff method was the main outcome. Other outcomes included vasodilation in isolated arteries and renal renin expression. RESULTS: Creatine kinase inhibition reduced BP safely and reversibly. Mean baseline BP of, respectively, 191.5 (standard error 4.3) mmHg SBP and 143.1 (4.1) mmHg DBP was reduced by, respectively, 42.7 (5.5) mmHg SBP and 35.6 (5.0) mmHg DBP (P < 0.001) compared with controls, with evidence of enhanced vasodilation and a diuretic effect. CONCLUSION: To our knowledge, this is the first report on the BP-lowering effect of creatine kinase inhibition. Our data indicate that modulation of the creatine kinase system is a potential novel treatment target for hypertension.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Creatina Quinase/antagonistas & inibidores , Guanidinas/farmacologia , Propionatos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Artérias/efeitos dos fármacos , Artérias/fisiopatologia , Diurese/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Rim/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Renina/metabolismo , Vasodilatação/efeitos dos fármacos
10.
Am J Hypertens ; 29(2): 170-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26048947

RESUMO

BACKGROUND: Creatine kinase (CK) is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility. We previously reported an association between vascular contractility and CK in normotensive pregnancy, but pregnancy is a strong CK inducer, and data on human hypertension are lacking. Therefore, we further explored CK-dependency of vascular contractility outside the context of pregnancy in normotensive and hypertensive women. METHODS AND RESULTS: Nineteen consecutive women, mean age 42 years (SE 1.3), mean systolic/diastolic blood pressure respectively 142.6 (SE 5.9)/85.6 (3.4) mm Hg (9 hypertensive), donated an omental fat sample during abdominal surgery. We compared vasodilation after the specific CK inhibitor 2,4-dinitro-1-fluorobenzene (DNFB; 10(-6) mol/l) to sodium nitroprusside (10(-6) mol/l) in isolated resistance arteries using a wire myograph. Additionally, we assessed predictors of vasoconstrictive force. DNFB reduced vascular contractility to 24.3% (SE 4.4), P < 0.001, compared to baseline. Sodium nitroprusside reduced contractility to 89.8% (SE 2.3). Maximum contractile force correlated with DNFB effect as a measure of CK (r = 0.8), and with vessel diameter (r = 0.7). The increase in contractile force was 16.5 mN [9.1-23.9] per unit DNFB effect in univariable and 10.35 mN [2.10-18.60] in multivariable regression analysis. CONCLUSION: This study extends on our previous findings in pregnant normotensive women of CK-dependent microvascular contractility, indicating that CK contributes significantly to resistance artery contractility across human normotension and primary hypertension outside the context of pregnancy. Further studies should explore the effect of CK inhibitors on clinical blood pressure.


Assuntos
Artérias/fisiologia , Creatina Quinase/metabolismo , Adulto , Pressão Sanguínea , Creatina Quinase/antagonistas & inibidores , Dinitrofluorbenzeno , Feminino , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade
12.
Trials ; 16: 56, 2015 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-25888414

RESUMO

BACKGROUND: Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population. In addition, the creatine analog and competitive oral creatine kinase inhibitor beta-guanidinopropionic acid effectively and safely reduced blood pressure in the spontaneously hypertensive rat. However, to our knowledge there are no human data on the safety of oral supplementation with this substance. Therefore, we will assess the tolerability of beta-guanidinopropionic acid in men, compared to creatine and placebo. METHODS/DESIGN: This is a randomized, active and placebo controlled, triple blind, double dummy, single center clinical intervention trial in 24 healthy male volunteers, 18 to 50 years old, recruited in the Netherlands. The intervention consists of one week of daily oral administration of beta-guanidinopropionic acid 100 mg, creatine 5 gram, or placebo. The primary outcome is the tolerability of beta-guanidinopropionic acid as a descriptive measure, in an intent-to-treat analysis. Other outcomes include the placebo-adjusted differences with baseline in biochemical and hemodynamic parameters, including plasma markers of muscle tissue damage, urine sodium excretion, resting sitting systolic and diastolic brachial blood pressure, supine systolic and diastolic central blood pressure, pulse wave velocity and augmentation index, heart rate, cardiac contractility, cardiac output, and total peripheral resistance. DISCUSSION: There is an unfulfilled need for new conservative options to treat resistant hypertension. This study will provide first-in-men data on creatine kinase inhibition as a potential new class of antihypertensive drugs. TRIAL REGISTRATION: The Netherlands National Trial Register Trialregister.nl (identifier NTR 4444) , registered 9 March 2014.


Assuntos
Protocolos Clínicos , Creatina Quinase/antagonistas & inibidores , Creatina/uso terapêutico , Guanidinas/uso terapêutico , Hipertensão/tratamento farmacológico , Propionatos/uso terapêutico , Adolescente , Adulto , Creatina Quinase/sangue , Método Duplo-Cego , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Nível de Efeito Adverso não Observado
13.
BMJ Open ; 4(12): e006380, 2014 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-25537786

RESUMO

INTRODUCTION: Obesity, hypertension and diabetes are on a dramatic rise in low-income and middle-income countries, and this foretells an overwhelming increase in chronic disease burden from cardiovascular disease. Therefore, rapid action should be taken through preventive population-based programmes. However, in these regions, data on the population distribution of cardiovascular risk factors, and of intermediate and final end points for cardiovascular disease are scarce. The Healthy Life in Suriname (HELISUR) study is a cardiovascular population study in Suriname, which is part of the Caribbean Community. The HELISUR study is dedicated to provide data on risk factors and prevalent cardiovascular disease in the multiethnic population, which is mainly of African and Asian descent. METHODS AND ANALYSIS: In a cross-sectional, observational population-based setting, a random representative sample of 1800 citizens aged between 18 and 70 years will be selected using a cluster household sampling method. Self-reported demographic, socioeconomic and (cardiovascular) health-related data will be collected. Physical examination will include the assessment of cardiovascular risk factors and prevalent cardiovascular disease. In addition, we will study cardiovascular haemodynamics non-invasively, as a novel intermediate outcome. Finally, fasting blood and overnight urine samples will be collected to monitor cardiometabolic risk factors. The main outcome will be descriptive in reporting the prevalence of risk factors and measures of (sub) clinical end organ damage, stratified for ethnicity and sex-age groups. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the State Secretary of Health. Data analysis and manuscript submission are scheduled for 2016. Findings will be disseminated in peer-reviewed journals, and at national, regional and international scientific meetings. Importantly, data will be presented to Surinamese policymakers and healthcare workers, to develop preventive strategies to combat the rapid rise of cardiovascular disease.


Assuntos
Doenças Cardiovasculares/epidemiologia , Nível de Saúde , Saúde , Adulto , Povo Asiático , Biomarcadores/sangue , Biomarcadores/urina , População Negra , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Estudos Transversais , Hemodinâmica , Humanos , Exame Físico , Prevalência , Projetos de Pesquisa , Fatores de Risco , Fatores Socioeconômicos , Suriname/epidemiologia
14.
Hypertension ; 63(1): 68-73, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24126179

RESUMO

Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of high resistance artery creatine kinase-BB rapidly regenerating ATP for vascular contractility. Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human resistance arteries are associated with blood pressure. We isolated resistance-sized arteries from omental fat donated by consecutive women undergoing uterine fibroid surgery. Blood pressure was measured in the sitting position. Vessels of 13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect correlation with diastolic blood pressure (correlation coefficient, 0.9; 95% confidence interval, 0.6-1.0) and were well correlated with systolic blood pressure, with a 90% relative increase in resistance artery creatine kinase B mRNA in hypertensives compared with normotensives, normalized copy numbers were, respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1), P=0.0045. To our knowledge, this is the first direct evidence suggesting that resistance artery creatine kinase mRNA expression levels concur with blood pressure levels, almost doubling with hypertension. These findings add to the evidence that creatine kinase might be involved in the vasculature's pressor responses.


Assuntos
Artérias/fisiopatologia , Pressão Sanguínea/fisiologia , Creatina Quinase/biossíntese , Hipertensão/fisiopatologia , Resistência Vascular/fisiologia , Adulto , Artérias/química , Artérias/metabolismo , Creatina Quinase/análise , Feminino , Expressão Gênica , Humanos , Hipertensão/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro
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