ABSTRACT
La hipertensión arterial (HTA), o presión arterial elevada, es una enfermedad que se caracteriza por la elevación persistente de la presión arterial sistólica >140 mmHg y diastólica >90 mmHg (1); la cual conlleva al incremento del riesgo de enfermedades en diferentes órganos como el corazón, cerebro, riñón, y otros (2). La Organización Panamericana de la Salud (OPS) menciona que el 20 al 40% de la población adulta padece de HTA, lo cual representa alrededor de 250 millones de personas en Las Américas (3). En el Perú, un estudio publicado en el 2021 mostró una prevalencia agregada de hipertensión de 22.0% (IC 95%: 20.0% - 25.0%; I2=99.2%), y una incidencia global de 4,2 (IC 95%: 2.0 6.4; I 2=98.6%) por cada 100 personas-año (4). El manejo oportuno y control de los factores de riesgo pueden mejorar el pronóstico de los pacientes con HTA, lo cual reduciría la mortalidad asociada principalmente a enfermedades cardiovasculares. Por ello, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia para gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.
Subject(s)
Humans , Adolescent , Adult , Blood Pressure Monitors , Essential Hypertension/drug therapy , Diet, Sodium-Restricted , Sodium Chloride Symporter Inhibitors/therapeutic use , Essential Hypertension/diagnosis , Heart Disease Risk Factors , Antihypertensive Agents/therapeutic useABSTRACT
Por medio de la presente queremos comentar acerca del artículo desarrollado por Góngora y otros (2021) acerca del Riesgo estimado de padecer diabetes mellitus tipo 2 (DM2) en pacientes hipertensos con tratamiento farmacológico.(1) Nos parece interesante la manera en la cual se ha desarrollado el artículo, sobre la relación que tiene la hipertensión arterial de debut como factor de riesgo directo para padecer DM2. Sin embargo, creemos que no se les da la debida importancia a otros factores con mayor predominio en el desarrollo de la DM2, como los que detallamos a continuación. Por ejemplo, Soares y otros (2014) demuestran que el factor de riesgo para DM2 más prevalente fue el sedentarismo, seguido por el exceso de peso, obesidad, glucosa plasmática e hipertensión arterial, todo esto ligado a malos hábitos alimenticios(2)(AU)
Subject(s)
Humans , Male , Female , Risk Factors , Diabetes Mellitus, Type 2/epidemiology , Feeding Behavior , Essential Hypertension/drug therapyABSTRACT
The development of essential hypertension involves several factors. Vascular dysfunction, characterized by endothelial dysfunction, low-grade inflammation and structural remodeling, plays an important role in the initiation and maintenance of essential hypertension. Although the mechanistic pathways by which essential hypertension develops are poorly understood, several pharmacological classes available on the clinical settings improve blood pressure by interfering in the cardiac output and/or vascular function. This review is divided in two major sections. The first section depicts the major molecular pathways as renin angiotensin aldosterone system (RAAS), endothelin, nitric oxide signalling pathway and oxidative stress in the development of vascular dysfunction. The second section describes the role of some pharmacological classes such as i) RAAS inhibitors, ii) dual angiotensin receptor-neprilysin inhibitors, iii) endothelin-1 receptor antagonists, iv) soluble guanylate cyclase modulators, v) phosphodiesterase type 5 inhibitors and vi) sodium-glucose cotransporter 2 inhibitors in the context of hypertension. Some classes are already approved in the treatment of hypertension, but others are not yet approved. However, due to their potential benefits these classes were included.
Subject(s)
Antihypertensive Agents , Hypertension , Humans , Antihypertensive Agents/pharmacology , Muscle, Smooth, Vascular/metabolism , Soluble Guanylyl Cyclase/metabolism , Neprilysin/metabolism , Nitric Oxide/metabolism , Essential Hypertension/drug therapy , Essential Hypertension/metabolism , Phosphodiesterase 5 Inhibitors/therapeutic use , Receptor, Endothelin A/metabolism , Hypertension/metabolism , Renin-Angiotensin System , Endothelins/metabolism , Endothelins/pharmacology , Endothelins/therapeutic use , Endothelin Receptor Antagonists/pharmacology , Receptors, Angiotensin/metabolism , Receptors, Angiotensin/therapeutic use , Glucose/metabolism , Sodium/metabolism , Sodium/pharmacology , Sodium/therapeutic useABSTRACT
Essential hypertension is considered to be a result of the interaction between genetic and environmental factors, including perinatal factors. Different advantageous perinatal factors proved to have beneficial long-lasting effects against an abnormal genetic background. Taurine is a ubiquitous sulphur-containing amino acid present in foods such as seafood. The antihypertensive effects of taurine have been reported in experimental studies and in human hypertension. We aimed to investigate the effects of perinatal treatment with taurine in spontaneously hypertensive rats (SHR), a known model of genetic hypertension. Female SHR were administered with taurine (3 g/L) during gestation and lactation (SHR-TAU). Untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. Long-lasting effects in offspring were investigated. Addition of taurine to the mother's drinking water reduced blood pressure in adult offspring. No differences were observed in cardiac hypertrophy. Findings on morphometric evaluations suggest that perinatal treatment with taurine would be partially effective in improving structural alterations of the aorta. Modifications in gene expression of Bcl-2 family members and upregulation of endothelial nitric oxide synthase in the aorta of 22-week-old male offspring were found. No differences were observed on relative telomere length in different cardiovascular tissues between SHR and SHR-TAU. Altogether results suggest that taurine programming, albeit sex specific, is associated with gene expression changes which ultimately may lead to improvement of aortic remodelling and enhanced endothelial function because of augmented nitric oxide (NO) production.
Subject(s)
Antihypertensive Agents/pharmacology , Aorta, Thoracic/drug effects , Blood Pressure/drug effects , Essential Hypertension/drug therapy , Nitric Oxide Synthase Type III/metabolism , Taurine/pharmacology , Animals , Aorta, Thoracic/enzymology , Aorta, Thoracic/physiopathology , Disease Models, Animal , Down-Regulation , Essential Hypertension/enzymology , Essential Hypertension/genetics , Essential Hypertension/physiopathology , Female , Gestational Age , Lactation , Male , Pregnancy , Prenatal Exposure Delayed Effects , Rats, Inbred SHR , Rats, Inbred WKY , Sex Factors , Signal TransductionABSTRACT
BACKGROUND: Angiotensin II is a potent activator of the Rho-kinase (ROCK) pathway, through which it exerts some of its adverse vasoconstrictor effects. Clinical evidence on the effects of blocking the angiotensin II receptor 1 on ROCK activity in hypertensive patients is scarce. OBJECTIVE: To demonstrate that ROCK activity in peripheral blood mononuclear cells (PMBCs) in patients with essential hypertension is reduced earlier than previously observed, along with blood pressure (BP) lowering on treatment with olmesartan. METHODS: Prospective pilot open study; 17 hypertensive patients were treated with progressive olmesartan doses starting with 20 mg qd. BP was measured at 3, 6 and 9 weeks after treatment initiation. If treatment failed to normalize BP after 3 weeks, olmesartan dose was increased to 40 mg qd, and if still hypertensive after 6 weeks, 12.5 mg of hydrochlorothiazide qd was added. ROCK activity was measured at baseline and 9 weeks after treatment as myosin phosphatase target subunit 1 phosphorylation (MYPT1-p/T ratio) in PBMC. RESULTS: Mean baseline BP was 162 ± 4.9/101 ± 2.4 mmHg. After 9 weeks of treatment, both systolic and diastolic BP were reduced by 41 and 22 mmHg, respectively (p<0.05). Mean pretreatment MYPT1- p/T ratio in PMBCs was significantly reduced by 80% after 9 weeks with olmesartan (p<0.01). CONCLUSION: Normotension achieved after 9 weeks in 82% of the patients treated with olmesartan was associated with a significant reduction of ROCK activity in PBMC.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/administration & dosage , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Essential Hypertension/drug therapy , Imidazoles/administration & dosage , Leukocytes, Mononuclear/drug effects , Tetrazoles/administration & dosage , rho-Associated Kinases/metabolism , Adult , Down-Regulation , Essential Hypertension/diagnosis , Essential Hypertension/enzymology , Essential Hypertension/physiopathology , Female , Humans , Leukocytes, Mononuclear/enzymology , Male , Middle Aged , Myosin-Light-Chain Phosphatase/metabolism , Phosphorylation , Pilot Projects , Prospective Studies , Time Factors , Treatment OutcomeABSTRACT
Generar recomendaciones basadas en la mejor evidencia disponible acerca del manejo de personas con Hipertensión Arterial esencial en personas de 15 años y más. Personas con Hipertensión Arterial esencial en personas de 15 años y más que reciben atención en el nivel primario, secundario y terciario de salud en el sector público y privado de salud.
Subject(s)
Humans , Adolescent , Essential Hypertension/prevention & control , Essential Hypertension/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Critical PathwaysABSTRACT
Abstract: Objective: To evaluate efficacy and safety of 60 mg and 120 mg Fimasartan (FMS) alone or combined with 12.5 mg hydrochlorothiazide (HCTZ) in a Mexican population. Methods: A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60 mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90 mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90 mmHg were randomised to either 120 mg FMS or 60 mg FMS + 12.5 mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90 mmHg received 120 mg FMS + 12.5 mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study. Results: FMS 60 mg (n = 272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3 ± 8.9 (p<.0001) and 16.0 ± 14.1 (p<.0001) mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120 mg, FMS 60 mg + HCTZ 12.5 mg, or FMS 120 mg + HCTZ 12.5 mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP < 90 mmHg and an SBP<140 mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%). Conclusion: Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.
Resumen: Objetivo: Evaluar la eficacia y la seguridad de 60 y 120 mg de fimasartán (FMS) solo o combinado con 12.5 mg de hidroclorotiazida (HCTZ) en población mexicana. Métodos: Estudio abierto, de 24 semanas, con tratamiento escalado hasta el objetivo terapéutico en sujetos hipertensos grados 1-2. Tratamiento inicial: FMS 60 mg una vez al día; en la semana 8, los sujetos con presión arterial diastólica (PAD) <90 mmHg mantuvieron su tratamiento inicial durante el estudio, mientras que los sujetos con PAD ≥90 mmHg fueron aleatorizados a 120 mg de FMS o a 60 mg de FMS + 12.5 mg de HCTZ. En la semana 12, los sujetos aleatorizados con PAD ≥90 mmHg recibieron 120 mg de FMS + 12.5 mg de HCTZ; quienes alcanzaron el objetivo terapéutico mantuvieron su tratamiento asignado hasta finalizar el estudio. Resultados: FMS 60 mg (n = 272) disminuyó la PAD y la presión arterial sistólica (PAS) en 11.3 ± 8.9 (p < 0.0001) y 16.0 ± 14.1 (p < 0.0001) mmHg, respectivamente, con logro del objetivo de tratamiento en el 75.4% de los sujetos. Los sujetos asignados a 120 mg de FMS, a 60 mg de FMS + 12.5 mg de HCTZ 12.5 y a 120 mg de FMS + 12.5 mg de HCTZ mostraron reducciones significativas de PAD y PAS; al final del estudio, 237/272 sujetos (87.1%) lograron PAD <90 y PAS <140 mmHg. Las reacciones adversas más frecuentemente reportadas fueron: cefalea (3.7%), boca seca (1.1%), incremento de enzimas hepáticas (1.1%) y mareo (0.7%). Conclusión: FMS es seguro y eficaz en sujetos mexicanos con hipertensión esencial de grados 1-2.
Subject(s)
Humans , Male , Female , Middle Aged , Pyrimidines/administration & dosage , Tetrazoles/administration & dosage , Biphenyl Compounds/administration & dosage , Essential Hypertension/drug therapy , Hydrochlorothiazide/administration & dosage , Antihypertensive Agents/administration & dosage , Pyrimidines/adverse effects , Tetrazoles/adverse effects , Biphenyl Compounds/adverse effects , Severity of Illness Index , Prospective Studies , Treatment Outcome , Drug Therapy, Combination , Mexico , Antihypertensive Agents/adverse effectsABSTRACT
Background There are few reviews comparing the long-term outcomes of the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in a hypertensive population because both are effective in reducing blood pressure. None of them compared angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with a placebo group in patients with essential hypertension, because few studies exist with this design. Methods A systematic search of PUBMED, LILACS, SCIELO, ICTRP, Cochrane, EMBASE and ClinicalTrials.gov from 1 January 2000 until 31 December 2015 selected prospective studies that reported an association between the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in the following cardiovascular outcomes: heart failure/hospitalisation, stroke, acute myocardial infarction, total cardiovascular deaths, total deaths and total outcomes. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were combined by using a fixed-effects model. Results Seventeen studies ( n = 73,761) were included of which 12 studies were randomly assigned to angiotensin II receptor blocker therapy ( n = 24,697) and five to angiotensin-converting enzyme inhibitors ( n = 12,170). Angiotensin-converting enzyme inhibitors proved to be significant in reducing total deaths (OR 0.85, 95% CI 0.78-0.93) and cardiovascular deaths (OR 0.77, 95% CI 0.69-0.87). Angiotensin II receptor blocker therapy did not show a reduction in total deaths (OR 1.02, 95% CI 0.96-1.09) or cardiovascular deaths (OR 0.95, 95% CI 0.86-1.06). For acute myocardial infarction, stroke and heart failure/hospitalisation, the reductions were significant for both classes. Conclusion Angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use is similar in preventing major cardiovascular outcomes regarding acute myocardial infarction, stroke and heart failure/hospitalisation. However, the use of angiotensin-converting enzyme inhibitors is more effective in reducing total deaths and cardiovascular deaths than angiotensin II receptor blockers.
Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Essential Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Aged , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Cause of Death , Chi-Square Distribution , Essential Hypertension/diagnosis , Essential Hypertension/mortality , Essential Hypertension/physiopathology , Female , Humans , Male , Middle Aged , Odds Ratio , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: This review covers the pharmacokinetics and pharmacodynamic of ß-blockers, the rationale for their use, some recent controversies in its use for managing hypertension, as well as, the beneficial properties of the third-generation ß-blockers beyond hypertension. BACKGROUND: The efficacy and safety of ß-blockers in the treatment of hypertension and other cardiovascular diseases have been established during more than 50 years of clinical experience. Recent updates of clinical guidelines have downgraded the use of ß-blockers for the treatment of uncomplicated hypertension to second and third line therapy. It is a well-known fact that ß-blockers exhibit heterogeneous pharmacokinetic and pharmacodynamic properties that clearly influence their clinical efficacy and tolerability in the management of essential hypertension. Conventional nonvasodilating ß-blockers (atenolol and metoprolol) are inferior to first-line antihypertensive agents in terms of cardioprotection due to lower ability to reduce central blood pressure and its variability and the adverse effects on glycemic and lipid metabolism. CONCLUSION: New vasodilating ß-blockers, mainly carvedilol and nebivolol, show enhanced hemodynamic and metabolic properties, which probably result in a higher prevention of major cardiovascular events in hypertensive patients. Despite head-to-head clinical trials comparing the effects of vasodilating vs nonvasodilating ß-blockers on hard clinical endpoints are lacking, the current evidence suggests that third-generation ß-blockers are superior to conventional ß-blockers for the prevention of cardiovascular events in patients with essential hypertension. Moreover, beyond their antihypertensive properties, third-generation ß-blockers also have pleiotropic, antioxidant and antiinflammatory effects that warrant a "promissory new era" of this newly group.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Antihypertensive Agents/therapeutic use , Essential Hypertension/drug therapy , Adrenergic beta-Antagonists/adverse effects , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Glycemic Index/drug effects , Humans , Lipid Metabolism/drug effectsABSTRACT
This study aimed to test the effects of xuezhikang, a cholestin extract that contains statin-like components, on arterial stiffness in patients with essential hypertension. One hundred hypertensive patients from the Chinese PLA General Hospital were randomly allocated to receive xuezhikang (1200 mg/day, orally) or placebo (same capsules containing only pharmaceutical excipients). Physical examination outcomes, lipid profile, high sensitivity C-reactive protein (hs-CRP) levels, matrix metalloproteinases-9 (MMP-9) levels, and arterial outcomes, including stiffness parameter (ß), pressure-strain elasticity modulus (Ep), arterial compliance (AC), augmentation index (AI), and one-point pulse wave velocity (PWVß) were obtained at baseline and after 6 months of the intervention. Xuezhikang significantly reduced ß (8.4±3.1 vs 6.8±2.1, P=0.007), Ep (122.8±43.9 vs 100.7±33.2, P=0.009), PWVß (6.7±1.2 vs 6.1±1.0, P=0.013), low-density lipoprotein cholesterol (3.4±0.6 vs 2.9±0.5, P=0.001), hs-CRP [2.1 (0.4-10.0) vs 1.4 (0.3-4.1), P=0.020], and MMP-9 (17.2±2.4 vs 12.7±3.8, P <0.001) compared to baseline. The placebo had no effect on these parameters. The changes of PWVß in the xuezhikang group was significantly associated with the changes of hs-CRP and MMP-9 (r=0.144, P=0.043; r=0.278, P=0.030, respectively) but not with lipid profile changes. Our research showed xuezhikang can improve the parameters of arterial stiffness in hypertensive patients, and its effect was independent of lipid lowering.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Essential Hypertension/drug therapy , Vascular Stiffness/drug effects , Drugs, Chinese Herbal/adverse effects , Essential Hypertension/blood , Essential Hypertension/physiopathology , Female , Humans , Lipids/blood , Male , Middle Aged , Pulse Wave Analysis , Vascular Stiffness/physiologyABSTRACT
PURPOSE: The aim of this study was to determine the gain and latency of arterial baroreflex control of heart rate in patients with resistant hypertension compared to patients with essential hypertension and normotensive subjects. METHODS: Eighteen patients with resistant hypertension (56 ± 10 years, mean of four antihypertensive drugs), 17 patients with essential hypertension (56 ± 11 years, mean of two antihypertensive drugs), and 17 untreated normotensive controls (50 ± 15 years) were evaluated by spectral analysis of the spontaneous fluctuations of arterial pressure (beat-to-beat) and heart rate (ECG). This analysis estimated vasomotor and cardiac autonomic modulations, respectively. The transfer function analysis quantified the gain and latency of the response of output signal (RR interval) per unit of spontaneous change of input signal (systolic arterial pressure). RESULTS: The gain was similarly lower in patients with resistant hypertension and patients with essential hypertension in relation to normotensive subjects (4.67 ± 2.96 vs. 6.60 ± 3.30 vs. 12.56 ± 8.81 ms/mmHg; P < 0.01, respectively). However, the latency of arterial baroreflex control of heart rate was significantly higher only in patients with resistant hypertension when compared to patients with essential hypertension and normotensive subjects (-4.01 ± 3.19 vs. -2.91 ± 2.10 vs. -1.82 ± 1.09 s; P = 0.04, respectively). In addition, the index of vasomotor sympathetic modulation was significantly increased only in patients with resistant hypertension when compared to patients with essential hypertension and normotensive subjects (4.04 ± 2.86 vs. 2.65 ± 1.88 vs. 2.06 ± 1.70 mmHg2; P < 0.01, respectively). CONCLUSIONS: Patients with resistant hypertension have reduced gain and increased latency of arterial baroreflex control of heart rate. These patients also have increased vasomotor sympathetic modulation.
Subject(s)
Baroreflex , Coronary Vasospasm/physiopathology , Hypertension/physiopathology , Muscle, Smooth, Vascular/physiopathology , Sympathetic Nervous System/physiopathology , Aged , Antihypertensive Agents/therapeutic use , Autonomic Nervous System/physiopathology , Electrocardiography , Essential Hypertension/drug therapy , Essential Hypertension/physiopathology , Female , Heart/innervation , Heart/physiopathology , Heart Rate , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: To evaluate efficacy and safety of 60mg and 120mg Fimasartan (FMS) alone or combined with 12.5mg hydrochlorothiazide (HCTZ) in a Mexican population. METHODS: A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90mmHg were randomised to either 120mg FMS or 60mg FMS + 12.5mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90mmHg received 120mg FMS+12.5mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study. RESULTS: FMS 60mg (n=272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3±8.9 (p<.0001) and 16.0±14.1 (p<.0001)mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120mg, FMS 60mg+HCTZ 12.5mg, or FMS 120mg+HCTZ 12.5mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP<90mmHg and an SBP<140mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%). CONCLUSION: Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.
Subject(s)
Antihypertensive Agents/administration & dosage , Biphenyl Compounds/administration & dosage , Essential Hypertension/drug therapy , Hydrochlorothiazide/administration & dosage , Pyrimidines/administration & dosage , Tetrazoles/administration & dosage , Antihypertensive Agents/adverse effects , Biphenyl Compounds/adverse effects , Drug Therapy, Combination , Essential Hypertension/classification , Female , Humans , Hydrochlorothiazide/adverse effects , Male , Mexico , Middle Aged , Prospective Studies , Pyrimidines/adverse effects , Severity of Illness Index , Tetrazoles/adverse effects , Treatment OutcomeABSTRACT
This study aimed to test the effects of xuezhikang, a cholestin extract that contains statin-like components, on arterial stiffness in patients with essential hypertension. One hundred hypertensive patients from the Chinese PLA General Hospital were randomly allocated to receive xuezhikang (1200 mg/day, orally) or placebo (same capsules containing only pharmaceutical excipients). Physical examination outcomes, lipid profile, high sensitivity C-reactive protein (hs-CRP) levels, matrix metalloproteinases-9 (MMP-9) levels, and arterial outcomes, including stiffness parameter (β), pressure-strain elasticity modulus (Ep), arterial compliance (AC), augmentation index (AI), and one-point pulse wave velocity (PWVβ) were obtained at baseline and after 6 months of the intervention. Xuezhikang significantly reduced β (8.4±3.1 vs 6.8±2.1, P=0.007), Ep (122.8±43.9 vs 100.7±33.2, P=0.009), PWVβ (6.7±1.2 vs 6.1±1.0, P=0.013), low-density lipoprotein cholesterol (3.4±0.6 vs 2.9±0.5, P=0.001), hs-CRP [2.1 (0.4-10.0) vs 1.4 (0.3-4.1), P=0.020], and MMP-9 (17.2±2.4 vs 12.7±3.8, P <0.001) compared to baseline. The placebo had no effect on these parameters. The changes of PWVβ in the xuezhikang group was significantly associated with the changes of hs-CRP and MMP-9 (r=0.144, P=0.043; r=0.278, P=0.030, respectively) but not with lipid profile changes. Our research showed xuezhikang can improve the parameters of arterial stiffness in hypertensive patients, and its effect was independent of lipid lowering.
Subject(s)
Humans , Male , Female , Middle Aged , Drugs, Chinese Herbal/therapeutic use , Essential Hypertension/drug therapy , Vascular Stiffness/drug effects , Drugs, Chinese Herbal/adverse effects , Essential Hypertension/blood , Essential Hypertension/physiopathology , Lipids/blood , Pulse Wave Analysis , Vascular Stiffness/physiologyABSTRACT
The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are associated with up-regulation of endothelial nitric oxide synthase (NOS3) activity. This mechanism may explain how polymorphisms in NOS3 gene affect the antihypertensive responses to ACEi. While clinically relevant NOS3 polymorphisms were previously shown to affect the antihypertensive responses to enalapril, no study has tested the hypothesis that NOS3 tagSNPs influence the antihypertensive effects of this drug. We examined whether the NOS3 tagSNPs rs3918226, rs3918188, and rs743506, and their haplotypes, affect the antihypertensive responses to enalapril in 101 patients with essential hypertension. Subjects were prospectively treated only with enalapril for 8 weeks. Genotypes were determined by Taqman(®) allele discrimination assay and real-time polymerase chain reaction (PCR) and haplotype frequencies were estimated. We compared the effects of NOS3 tagSNPs on changes in blood pressure after enalapril treatment. To confirm our findings, multiple linear regression analysis was performed adjusting for age, gender, ethnicity, and alcohol consumption. We found that hypertensive patients carrying the AA genotype for the tagSNP rs3918188 showed lower decreases in blood pressure in response to enalapril. Moreover, the TCA haplotype was associated with improved decreases in blood pressure in response to enalapril compared with the CAG haplotype. Adjustment for covariates in multiple linear regression analysis did not change these effects. In addition, when patients were stratified according to the dose of enalapril used, we found that the carries of the T allele for the functional tagSNP rs3918226 showed more intense decreases in blood pressure in response to enalapril 20 mg/day. Our findings suggest that NOS3 tagSNPs influence the effects of enalapril in essential hypertension.