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1.
Hypertension ; 75(6): 1584-1592, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32336236

RESUMO

Blood pressure-lowering drugs have different blood pressure-lowering profiles. We studied if differences in blood pressure mean and variability can explain the differences in risks of cardiovascular events and death among 15 245 high-risk hypertensive patients randomized to valsartan or amlodipine and followed for 4.2 years in the VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation). We selected patients with ≥3 visits and performed Cox regression analyses, defining mean blood pressure as a time-dependent covariate and visit-to-visit and within-visit blood pressure variability as the SD. Of 14 996 eligible patients, participants in the valsartan group had higher systolic mean blood pressure by 2.2 mm Hg, higher visit-to-visit systolic variability by 1.4 mm Hg, and higher within-visit systolic variability by 0.2 mm Hg (P values <0.0001). The higher risks of myocardial infarction and stroke in the valsartan group was attenuated after adjustment for mean and variability of systolic blood pressure, from HR 1.19 (95% CI, 1.02-1.39) to 1.11 (0.96-1.30) and from HR 1.13 (0.96-1.33) to 1.00 (0.85-1.18), respectively. The lower risk of congestive heart failure in the valsartan group was accentuated after adjustment, from HR 0.86 (0.74-1.00) to 0.76 (0.65-0.89). A smaller effect was seen on risk of death, from 1.01 (0.92-1.12) to 0.94 (0.85-1.04). In conclusion, the higher risks of myocardial infarction and stroke in patients randomized to valsartan versus amlodipine were related to the drugs' different blood pressure modulating profiles. The risk of congestive heart failure with valsartan was lower, independent of the less favorable blood pressure modulating profile.

2.
Hypertension ; 75(1): 23-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786973

RESUMO

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.

3.
J Hypertens ; 37(12): 2333-2340, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31335513

RESUMO

: In quadrupeds, the arterial baroreflex has dominance in the reflex homeostatic responses, which protect against haemorrhage. In humans, it is the low pressure cardiopulmonary reflex, which protects against the analogous cardiovascular challenge of gravity-dependent venous pooling with standing. To preserve orthostatic cardiovascular homeostasis with the emergence of bipedalism in humans the low pressure reflex, a minor, subsidiary reflex in quadripeds, was co-opted. Mirroring the imperfect skeletal evolution to bipedalism, this cardiovascular development has been problematic, with dysregulation manifesting as disabling orthostatic intolerance syndromes and, paradoxically, an orthostatic hypertensive response that appears to play a role in the development of essential hypertension in some people. Improved understanding of these evolutionary faults provides new options for postural and pharmacological treatments.

4.
J Hypertens ; 36(6): 1222-1236, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29570514

RESUMO

: Whether isolated systolic hypertension in the young (ISHY) implies a worse outcome and needs antihypertensive treatment is still a matter for dispute. ISHY is thought to have different mechanisms than systolic hypertension in the elderly. However, findings from previous studies have provided inconsistent results. From the analysis of the literature, two main lines of research and conceptualization have emerged. Simultaneous assessment of peripheral and central blood pressure led to the identification of a condition called pseudo or spurious hypertension, which was considered an innocent condition. However, an increase in pulse wave velocity has been found by some authors in about 20% of the individuals with ISHY. In addition, obesity and metabolic disturbances have often been documented to be associated with ISHY both in children and young adults. The first aspect to consider whenever evaluating a person with ISHY is the possible presence of white-coat hypertension, which has been frequently found in this condition. In addition, assessment of central blood pressure is useful for identifying ISHY patients whose central blood pressure is normal. ISHY is infrequently mentioned in the guidelines on diagnosis and treatment of hypertension. According to the 2013 European Guidelines on the management of hypertension, people with ISHY should be followed carefully, modifying risk factors by lifestyle changes and avoiding antihypertensive drugs. Only future clinical trials will elucidate if a benefit can be achieved with pharmacological treatment in some subgroups of ISHY patients with associated risk factors and/or high central blood pressure.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/epidemiologia , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial/métodos , Criança , Europa (Continente)/epidemiologia , Humanos , Hipertensão/diagnóstico , Estilo de Vida , Pessoa de Meia-Idade , Obesidade/diagnóstico , Guias de Prática Clínica como Assunto , Prevalência , Prognóstico , Análise de Onda de Pulso , Fatores de Risco , Sociedades Médicas , Hipertensão do Jaleco Branco/diagnóstico , Adulto Jovem
5.
Eur Heart J ; 39(24): 2243-2251, 2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29365085

RESUMO

Aims: Blood pressure variability is associated with increased risk of cardiovascular events, particularly in high-risk patients. We assessed if variability was associated with increased risk of cardiovascular events and death in hypertensive patients at different risk levels. Methods and results: The Valsartan Antihypertensive Long-term Use Evaluation trial was a randomized controlled trial of valsartan vs. amlodipine in patients with hypertension and different risks of cardiovascular events, followed for a mean of 4.2 years. We calculated standard deviation (SD) of mean systolic blood pressure from visits from 6 months onward in patients with ≥3 visits and no events during the first 6 months. We compared the risk of cardiovascular events in the highest and lowest quintile of visit-to-visit blood pressure variability, using Cox regression. For analysis of death, variability was analysed as a continuous variable. Of 13 803 patients included, 1557 (11.3%) had a cardiovascular event and 1089 (7.9%) died. Patients in the highest quintile of SD had an increased risk of cardiovascular events [hazard ratio (HR) 2.1, 95% confidence interval (95% CI) 1.7-2.4; P < 0.0001], and a 5 mmHg increase in SD of systolic blood pressure was associated with a 10% increase in the risk of death (HR 1.10, 95% CI 1.04-1.17; P = 0.002). Associations were stronger among younger patients and patients with lower systolic blood pressure, and similar between patients with different baseline risks, except for higher risk of death among patients with established cardiovascular disease. Conclusion: Higher visit-to-visit systolic blood pressure variability is associated with increased risk of cardiovascular events in patients with hypertension, irrespective of baseline risk of cardiovascular events. Associations were stronger in younger patients and in those with lower mean systolic blood pressure.


Assuntos
Insuficiência Cardíaca/epidemiologia , Hipertensão/fisiopatologia , Mortalidade , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Valsartana/uso terapêutico
6.
J Hypertens ; 34(10): 2103-4, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27579707
7.
J Hypertens ; 34(5): 813-21, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26982382

RESUMO

In June 2015, a panel of experts gathered in a consensus conference to plan updating recommendations on the management of the hypertensive patient with elevated heart rate (HR), previously released in 2006. The issues examined during that meeting and further discussed by the participants during the following months involved the assessment of HR, the relevance of HR as a cardiovascular risk factor, the definition of tachycardia and the treatment of the hypertensive patient with high HR. For the measurement of resting HR the panel experts recommended that scientific investigations focusing on HR should report information on length of resting period before measurement, information about temperature and environment, method of measurement, duration of measurement, number of readings, time interval between measurements, body position and type of observer. According to the panellists there is convincing evidence that HR is an important risk factor for cardiovascular disease and they suggest to routinely include HR measurement in the assessment of the hypertensive patient. Regarding the definition of tachycardia, the panellists acknowledged that in the absence of convincing data any threshold used to define tachycardia is arbitrary. Similarly, as there are no outcome studies of HR lowering in tachycardia hypertension, the panellists could not make practical therapeutic suggestions for the management of such patients. However, the experts remarked that absence of evidence does not mean evidence against the importance of tachycardia as a risk factor for cardiovascular disease and that long-term exposure to a potentially important risk factor may impair the patient's prognosis. The main aims of the present document are to alert researchers and physicians about the importance of measuring HR in hypertensive patients, and to stimulate research to clarify unresolved issues.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Taquicardia/complicações , Anti-Hipertensivos/administração & dosagem , Conferências de Consenso como Assunto , Gerenciamento Clínico , Europa (Continente) , Frequência Cardíaca , Humanos , Hipertensão/complicações , Monitorização Ambulatorial , Sociedades Médicas
8.
Blood Press ; 25(4): 235-40, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26808585

RESUMO

Diabetic and new-onset diabetic patients with hypertension have higher cardiac morbidity than patients without diabetes. We aimed to investigate whether baseline predictors of cardiac morbidity, the major constituent of the primary endpoint in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, were different in patients with diabetes and new-onset diabetes compared to patients without diabetes. In total, 15,245 high-risk hypertensive patients in the VALUE trial were followed for an average of 4.2 years. At baseline, 5250 patients were diabetic by the 1999 World Health Organization criteria, 1298 patients developed new-onset diabetes and 8697 patients stayed non-diabetic during follow-up. Cardiac morbidity was defined as a composite of myocardial infarction and heart failure requiring hospitalization, and baseline predictors were identified by univariate and multivariate stepwise Cox regression analyses. History of coronary heart disease (CHD) and age were the most important predictors of cardiac morbidity in both diabetic and non-diabetic patients. History of CHD, history of stroke and age were the only significant predictors of cardiac morbidity in patients with new-onset diabetes. Predictors of cardiac morbidity, in particular history of CHD and age, were essentially the same in high-risk hypertensive patients with diabetes, new-onset diabetes and without diabetes who participated in the VALUE trial.


Assuntos
Anti-Hipertensivos/uso terapêutico , Complicações do Diabetes/complicações , Insuficiência Cardíaca/etiologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/etiologia , Valsartana/uso terapêutico , Anlodipino/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Complicações do Diabetes/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/fisiopatologia , Fatores de Risco
9.
Blood Press ; 25(2): 83-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26511535

RESUMO

Previous studies have debated the notion that low blood pressure (BP) during treatment, particularly diastolic (DBP), is associated with increased risk of cardiovascular disease. We evaluated the impact of low BP on cardiovascular outcomes in a high-risk population of 15,244 hypertensive patients, almost half of whom had a history of coronary artery disease (CAD). In the prospective Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, patients were randomized to valsartan or amlodipine regimens and followed for 4.2 years (mean) with no difference in the primary cardiovascular endpoint. A Cox proportional hazards model was used to evaluate the relationship between average on-treatment BP and clinical outcomes. The relationship between BP and cardiovascular events was adjusted for age, gender and body mass index, and baseline qualifying risk factors and diseases (smoking, high total cholesterol, diabetes mellitus, proteinuria, CAD, previous stroke and left ventricular hypertrophy). DBP ≥ 90 mmHg, compared with < 90 mmHg, was associated with increased incidence of the primary cardiovascular endpoint (all cardiac events); however, DBP < 70 mmHg, compared with ≥ 70 mmHg, was not associated with increased incidence after covariate adjustment (no J-shaped curve). Similar results were observed for death, myocardial infarction (MI), heart failure and stroke, considered separately. Nadir for MI was at DBP of 76 mmHg and for stroke 60 mmHg. The ratio of MI to stroke increased with lower DBP. In CAD patients the MI to stroke ratio was more pronounced than in patients without CAD but there was no significant J-curve in either group. Systolic BP ≥ 150 but not < 130 mmHg, compared with 130-149 mmHg, similarly was associated with increased risk for primary outcome. In conclusion, patients in BP strata ≥ 150/90 mmHg, but not patients in BP strata < 130/70 mmHg, were at increased risk for adverse outcomes in this hypertensive, high-risk population. Although benefit in preventing MI in relation to preventing stroke levels off for the lowest BPs, these data provide no support for a J-curve in the treatment of high-risk hypertensive patients . The increase in the ratio of MI to stroke with lower DBP indicates target organ heterogeneity in that the optimal on-treatment DBP for cerebroprotection is below that for cardioprotection.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doença da Artéria Coronariana/diagnóstico , Hipertensão/diagnóstico , Infarto do Miocárdio/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Valsartana/uso terapêutico , Idoso , Determinação da Pressão Arterial , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/fisiopatologia , Diástole , Método Duplo-Cego , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Sístole , Resultado do Tratamento
10.
Eur Heart J ; 37(12): 955-64, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26590384

RESUMO

AIMS: Recent hypertension guidelines recommend that also in high cardiovascular (CV) risk, hypertensive patients blood pressure (BP) is lowered to <140/90 mmHg as no evidence is available supporting the lower target of <130/80 mmHg recommended in previous guidelines. Whether this represents the optimal treatment strategy is debated, however. METHODS AND RESULTS: The high CV risk hypertensive patients of the Valsartan Antihypertensive Long-term use Evaluation (VALUE) trial were divided into subgroups according to (i) the percentage of on-treatment visits in which BP was reduced to <140/90 or <130/80 mmHg or (ii) the mean systolic or diastolic BP (SBP/DBP) values achieved during the entire treatment period or up to the occurrence of an event. A progressive increase from <25 to ≥75% of the visits in which BP was <140/90 mmHg was accompanied by a significant, progressive marked decrease in the covariate adjusted risk of CV morbidity and mortality, cause specific CV events (myocardial infarction, heart failure, and stroke), and all-cause mortality. Except for a persistent progressive decrease in stroke, no significant trend to a risk decrease occurred for a similar progressive increment of the proportion of visits with BP <130/80 mmHg. Increasing the proportion of visits with a BP <140/90 mmHg (but not <130/80 mmHg) was accompanied by a decreased risk of events also when differences in baseline risk were adjusted using a propensity score. Finally, compared with patients remaining at a mean on-treatment SBP ≥140 or DBP ≥90 mmHg, the risk of all events was markedly reduced when on-treatment mean SBP was lowered to a mean SBP of 130-139 mmHg or a mean DBP of 80-89 mmHg, whereas at on-treatment mean SBP <130 mmHg or DBP <80 mmHg, an additional risk reduction was found for stroke but for any other type of event, the risk of which remained similar or only slightly greater than that seen at the higher BP target. CONCLUSIONS: In the high CV risk, hypertensives of the VALUE trial reducing BP consistently to <140/90 mmHg had marked beneficial effects both when data were calculated as proportion of visits at BP target or as on-treatment mean BP. Reducing BP to <130/80 mmHg led only to some possible further benefit on stroke, whereas the risk of other outcomes remained substantially similar to or slightly greater than that seen at the higher target. Thus, aggressive BP reductions when CV risk is high may not offer substantial advantages, except perhaps in patients or conditions in which stroke risk is particularly common.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Valsartana/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Masculino , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/prevenção & controle , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
11.
Blood Press ; 24(1): 1-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25162203

RESUMO

BACKGROUND: Treatment of resistant hypertension has attained much attention during the past few years and naturally so has the prevalence of resistant hypertension. In the search for sources of such documentation, the lack of blood pressure (BP) control in randomized clinical outcome trials in hypertension has been used as indication of treatment-resistant hypertension. In the present study, we aimed at using previously unpublished information from monitoring of clinical trials in investigating the mechanism explaining why large fractions of patients in the trials remained uncontrolled for their high BP. METHODS: We report insight information from LIFE (n = 9193), VALUE (n = 15,245), ASCOT (n = 19,257) and ACCOMPLISH (n = 11,506). Data stored during the course of the trials for monitoring purposes were scrutinized for fractions of patients with BP control, which was BP < 140/90 mmHg in all trials, and we identified monitoring data showing fractions of patients who had been uptitrated to the various dosing levels or combinations of study drugs in the trials. Fractions of patients who had not been uptitrated on drugs and who remained without BP control identified the level of physician (investigator) inertia in these trials. RESULTS: In the LIFE Study the majority of patients remained with systolic BP > 140 mmHg throughout. Approximately 1500 patients remained on the first dose titration step despite not having reached target BP. In the VALUE Trial 59.5% had reached systolic BP target 2 years into the study; 23.9% of patients remained on the lowest study dose and only 15.1% had been uptitrated to the highest study dose. In the ASCOT Trial, as many as 28% of participants had not reached target diastolic BP at year 4 in the study, and of these patients 37% still remained on the first drug dose titration step. In the ACCOMPLISH Trial approximately 80% had achieved the systolic BP target at study end; however, during the course of the trial approximately 25% of participants remained uncontrolled and at 6 months almost 60% of these patients had not been titrated to the highest drug dose level. CONCLUSION: These data, taken from the monitoring phases of large outcome trials in hypertension, show that inertia, the lack of titration of study drugs to higher dosing levels or drug combinations according to the study protocols, is a major cause of not reaching BP targets in the trials. Thus, fractions of patients not reaching BP targets in outcome trials cannot be taken as evidence of treatment-resistant hypertension.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Médicos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Stroke Cerebrovasc Dis ; 23(10): 2814-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25304725

RESUMO

BACKGROUND: Risk factors for first stroke are well established, but less is known about risk factors for recurrent stroke. In the present analysis, we aimed to assess the effect of heart rate and other possible predictors of stroke in a hypertensive population with previous stroke or transient ischemic attack (TIA). METHODS: The Valsartan Antihypertensive Long-Term Use Evaluation trial was a multicentre, double-masked, randomized controlled, parallel group trial comparing the effects of an angiotensin receptor blocker (valsartan) and a calcium channel blocker (amlodipine) in patients with hypertension and high cardiovascular risk. We used Cox proportional hazard models to investigate the effect of baseline variables on the risk of stroke. Quadratic terms of the continuous variables were entered in the models to test for linearity. RESULTS: Of 15,245 patients included in the trial, 3014 had a previous stroke or TIA at baseline and were included in the present analysis. Stroke recurrence occurred in 239 patients (7.9%) during a median of 4.5 years of follow-up. Resting heart rate (per 10 beats per minute; hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.18-6.58) and diabetes mellitus at baseline (HR, 1.47; 95% CI, 1.03-2.10) were significantly associated with an increased risk of stroke recurrence in the multivariable analysis. CONCLUSIONS: In high-risk, hypertensive patients with previous stroke or TIA, resting heart rate was the strongest predictor of recurrent stroke.


Assuntos
Frequência Cardíaca , Hipertensão/complicações , Ataque Isquêmico Transitório/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Tetrazóis/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Valina/análogos & derivados , Valina/uso terapêutico , Valsartana
14.
Hypertension ; 63(6): 1182-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24591335

RESUMO

Systolic blood pressure (SBP) rises approximately linearly with age in most societies. The cause of this rise is unclear. We tested the hypothesis that SBP is causally associated with the rate of rise in SBP with age by evaluating the effect of 12 polymorphisms associated with lower SBP on the age-related rate of rise in SBP in a series of meta-regression analyses involving ≤199 477 participants in 63 studies. We then evaluated the effect of these polymorphisms on the odds of coronary heart disease in 22,223 case and 64,762 control subjects and compared it with the effect of lower SBP observed in both prospective cohort studies and blood pressure-lowering randomized trials. All 12 polymorphisms were associated with both lower SBP and a slower age-related rise in SBP. The weighted mean effect of these 12 polymorphisms was associated with a 0.32-mm Hg lower SBP (P=1.79×10(-7)) and a 0.093-mm Hg/decade slower age-related rise in SBP (P=3.05×10(-5)). The effect of long-term exposure to lower SBP on coronary heart disease mediated by these polymorphisms was 2-fold greater than that observed in prospective cohort studies (P=0.006) and 3-fold greater than that observed in short-term blood pressure treatment trials (P=0.001). We conclude therefore that SBP seems to be causally associated with the rate of rise in SBP with age and has a cumulative effect on the risk of coronary heart disease.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Fatores Etários , Criança , Doença das Coronárias/genética , Doença das Coronárias/fisiopatologia , Doença das Coronárias/prevenção & controle , Frequência do Gene , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Hipertensão/genética , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Metanálise como Assunto , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
15.
Am J Hypertens ; 27(7): 966-72, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24552888

RESUMO

BACKGROUND: Blacks have a higher prevalence of risk factors for atrial fibrillation (AF), such as hypertension, obesity, and heart failure, than nonblacks. Although population-based studies have demonstrated a lower prevalence and incidence of AF in blacks, the relationship of incident AF to race among hypertensive patients undergoing blood pressure lowering has been less extensively examined. METHODS: Incident AF was examined in 518 black and 8,313 nonblack hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) with no history of AF in sinus rhythm on their baseline electrocardiogram, who were randomly assigned to losartan- or atenolol-based treatment. RESULTS: During a mean of 4.7±1.1 years of follow-up, new-onset AF occurred in 701 patients (7.9%); 5-year AF incidence was significantly lower in black than nonblack patients (6.1 vs. 8.3%; P = 0.03). In univariable Cox analyses, black race was associated with a 37% lower risk of new AF (hazard ratio (HR) = 0.63; 95% confidence interval (CI) = 0.45-1.00; P = 0.05). In multivariable Cox analyses adjusting for randomized treatment, age, sex, diabetes, history of heart failure, myocardial infarction, ischemic heart disease, stroke, peripheral vascular disease, smoking status, baseline body mass index, serum total and high-density lipoprotein cholesterol, creatinine, glucose, and urine albumin/creatinine ratio as standard risk factors, and for incident myocardial infarction, in-treatment heart rate, systolic and diastolic pressure, Cornell product, and Sokolow-Lyon voltage LVH treated as time-varying covariables, black race remained associated with a 45% decreased risk of developing new AF (HR = 0.55; 95% CI = 0.35-0.87; P = 0.01). CONCLUSIONS: Incident AF is substantially less common among black than nonblack hypertensive patients.


Assuntos
Fibrilação Atrial/epidemiologia , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Grupo com Ancestrais do Continente Africano , Idoso , Anti-Hipertensivos/uso terapêutico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
16.
J Hypertens ; 32(2): 251-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24275841

RESUMO

BACKGROUND: Previous studies reported increased white blood cell counts (WBCCs), an inflammatory marker, in hypertension, prehypertension and metabolic syndrome. Evidence suggests that inflammation precedes blood pressure (BP) elevation and may contribute to incident hypertension. Angiotensin receptor blockers (ARBs) may reduce inflammation. We analyzed WBCC trends in TRial Of Preventing HYpertension (TROPHY) to determine if this inflammatory marker predicted incident hypertension in prehypertensive individuals and whether randomized assignment to the ARB candesartan (391 individuals) for 2 years, lowered WBCC compared with placebo-treated controls (381 individuals). METHODS: A new analysis of TROPHY trial data. RESULTS: In the total population, baseline BMI correlated with WBCC (r = 0.185, P < 0.0001), neutrophils (r = 0.135, P < 0.001) and lymphocytes (r = 0.204, P < 0.0001). Baseline triglycerides also correlated significantly with inflammatory markers. Despite a wide range of home BP (HBP) values, HBP did not correlate with baseline WBCC counts. After 2 years, candesartan decreased placebo corrected HBP by -5.5/-2.5 mmHg, (P < 0.0001), but WBCC, neutrophil and lymphocyte counts were not different in placebo and in candesartan groups. Baseline WBCC, neutrophils and lymphocyte counts did not predict incident hypertension in the placebo group. CONCLUSION: In TROPHY, candesartan lowered BP but did not alter WBCC. Baseline WBCC did not predict incident hypertension. Our findings do not support the hypothesis that inflammation contributes to incident hypertension or that ARB treatment suppresses inflammation. The significant independent association of WBCC with baseline BMI and triglycerides is consistent with the evidence that obesity and insulin resistance are associated with inflammation. The findings highlight the importance of effective lifestyle modification in prehypertension to reduce inflammatory cardio-metabolic risk and suppress transition to hypertension.


Assuntos
Hipertensão/prevenção & controle , Leucocitose/complicações , Pré-Hipertensão/complicações , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Benzimidazóis/uso terapêutico , Pressão Sanguínea , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Humanos , Hipertensão/etiologia , Inflamação/complicações , Inflamação/tratamento farmacológico , Contagem de Leucócitos , Leucocitose/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pré-Hipertensão/tratamento farmacológico , Fatores de Risco , Tetrazóis/uso terapêutico
17.
Am J Hypertens ; 26(12): 1381-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24190927

RESUMO

BACKGROUND: Recently, we reported that transient treatment of genetically hypertensive rats with high-dose angiotensin receptor blocker (ARB) causes regression of established hypertension. In this study, we investigated whether treatment with candesartan or nifedipine controlled-release (CR) resulted in a sustained regression of hypertension in humans. METHODS: Patients aged 30 to 59 years with untreated stage 1 essential hypertension and a family history of hypertension were treated with the antihypertensive agents candesartan (n = 124) or nifedipine CR (n = 120). After 1 year of treatment (phase 1), the medications were tapered and discontinued (phase 2). During phase 2, home and office blood pressures were monitored for another year to assess posttreatment reoccurrence of stage 1 hypertension. RESULTS: In phase 1, after 1 year of treatment a similarly substantial BP decrease was seen in the candesartan (-24.5/16.1 mm Hg) and nifedipine (-26.8/18.0 mm Hg) groups. In phase 2 there was a substantial reoccurrence of hypertension; at the study end, only 1 patient was able to continue without antihypertensive medication. However, a Kaplan-Meier analysis revealed a significant delay of reoccurrence of hyper tension (P = 0.0001) in the candesartan group. CONCLUSIONS: One year of treatment with candesartan or nifedipine CR was not associated with marked regression of hypertension in humans at the standard doses used in this trial. However, withdrawal of candesartan was associated with a slightly longer delay before restarting medications. Further studies with larger doses of candesartan given over a longer time are required to determine whether such a regimen may induce sustainable and clinically relevant reversal of hypertension and alteration in its natural history.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Nifedipino/uso terapêutico , Tetrazóis/uso terapêutico , Adulto , Anti-Hipertensivos/administração & dosagem , Benzimidazóis/administração & dosagem , Determinação da Pressão Arterial , Método Duplo-Cego , Esquema de Medicação , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Hipertensão/dietoterapia , Hipertensão/fisiopatologia , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nifedipino/administração & dosagem , Estudos Prospectivos , Tetrazóis/administração & dosagem , Resultado do Tratamento
19.
J Clin Hypertens (Greenwich) ; 14(11): 744-50, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23126345

RESUMO

Visit-to-visit variability (VVV) of blood pressure is associated with cardiovascular disease. The authors examined the effects of visit number and timing and automated or manual measurement device on VVV in the placebo arm of the Trial of Preventing Hypertension (TROPHY) (N=225) and simulations. VVV was assessed using intra-individual standard deviation (SD), range, maximum, coefficient of variation, successive variation, and average real variability of systolic blood pressure. VVV increased with number of visits used to calculate it in the TROPHY population (P for trend <.05 for all metrics) and simulations. Using consecutive visits in TROPHY, average SD was 5.6 mm Hg from 3 visits, 6.8 mm Hg from 7 visits, and 7.7 mm Hg from 18 visits. When 7 visits were spread out across 4 years, the average SD was higher (7.5 mm Hg) than when visits were consecutive over 18 months (P<.001). SD was higher using a single blood pressure measurement per visit (compared with the mean of 3 measurements per visit P<.001) and with automated vs manual devices (P<.001). In summary, number and timing of visits and device used to measure blood pressure influence VVV and need to be considered when designing, interpreting, and comparing studies.


Assuntos
Determinação da Pressão Arterial/instrumentação , Visita a Consultório Médico , Adulto , Idoso , Determinação da Pressão Arterial/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
20.
J Hypertens ; 30(11): 2213-22, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23011525

RESUMO

OBJECTIVES: To determine whether blood pressure (BP) control in hypertensive patients achieved with combination drug therapy provides the same cardiovascular benefits as with single-agent therapy. BACKGROUND: Drug combinations, most often including hydrochlorothiazide (HCTZ), are now recommended for routine BP management, but their effects on cardiovascular event rates have not been compared with effective monotherapy. METHODS: We conducted retrospective analyses of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) data. VALUE compared cardiovascular event rates of valsartan and amlodipine. Patients with BPs not controlled (<140/90  mmHg) by the single agents had HCTZ and, if required, additional drugs of different classes, added. Using data pooled from the two treatment arms, we have now divided patients into those controlled on monotherapy and those controlled or not controlled by combination therapy. The primary study endpoint was first occurrence of cardiovascular death or nonfatal myocardial infarction or stroke. Comparisons between groups were by Cox regression, adjusted for on-treatment BP, age, prior cardiovascular events and left ventricular hypertrophy; the comparison between the monotherapy and combination therapy controlled groups was based on events occurring after 3 months by when the decision to use monotherapy or combination therapy was made. RESULTS: The primary endpoint occurred in 505 of 5924 (8.5%) monotherapy and 511 of 4621 (11.1%) combination therapy controlled patients: hazard ratio was 0.80 [95% confidence interval (CI) 0.70-0.90]. If these two groups were matched for baseline BPs and all events included from study baseline, the hazard ratio was 0.76 (95% CI 0.67-0.86). The difference between combination controlled and uncontrolled [434 of 3390 (12.8%)] groups was not significant [hazard ratio 0.90 (95% CI 0.80-1.03], nor when they were matched for baseline BPs [hazard ratio 0.95 (95% CI 0.81-1.11)]. CONCLUSION: Independent of prior cardiovascular history or baseline BP, hypertensive patients requiring combination therapy, which includes a thiazide diuretic for BP control, have a poorer cardiovascular prognosis than those controlled by monotherapy and only a nonsignificantly lower event rate than noncontrolled patients.


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Idoso , Anlodipino/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hipertensão/fisiopatologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/prevenção & controle , Tetrazóis/administração & dosagem , Resultado do Tratamento , Valina/administração & dosagem , Valina/análogos & derivados , Valsartana
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