RESUMEN
BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.
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Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/prevención & control , Tasa de Filtración Glomerular , Hipertensión/complicaciones , Hipertensión/terapia , Sístole , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Análisis de Regresión , Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear. METHODS: SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP. RESULTS: Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level (P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events. CONCLUSIONS: Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.
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Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Síndrome Coronario Agudo/epidemiología , Anciano , Anciano de 80 o más Años , Antihipertensivos/efectos adversos , Diástole/efectos de los fármacos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/mortalidad , Hipertensión/fisiopatología , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Puerto Rico , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events. STUDY DESIGN: Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease. INTERVENTIONS: Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm). OUTCOMES & MEASUREMENTS: Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event. RESULTS: There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively. LIMITATIONS: Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease. CONCLUSIONS: More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01206062.
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Lesión Renal Aguda/prevención & control , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Lesión Renal Aguda/etiología , Anciano , Determinación de la Presión Sanguínea , Cuidados Críticos/métodos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estándares de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
Rationale & Objective: Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship. Study Design: Retrospective cohort study. Setting & Participants: 24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to 2013. Exposures: AKI, AKI severity, and age. Outcomes: KFRT and death. Analytical Approach: The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death. Results: Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity. Limitations: Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity. Conclusions: In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT.
Older adults are at risk of acute kidney injury (AKI) and subsequent nonrecovery from AKI, resulting in long-term dialysis. Hospitalized patients have often been used in the past to study AKI. This could lead to biased conclusions when inferring from sicker populations. That is why we created a national cohort of 24,133 Veterans at least 65 years old with incident chronic kidney disease (CKD) stage 4 to examine the relationship between AKI and age and subsequent kidney failure with replacement therapy (KFRT). The data have showed that AKI and younger age are substantial risk factors for incident KFRT. As for older age, it appears to be protective against KFRT but not death. This is likely explained by the high frequency of deaths observed in our cohort.
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[Figure: see text].
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Antihipertensivos/farmacología , Aorta/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Rigidez Vascular/efectos de los fármacos , Anciano , Antihipertensivos/uso terapéutico , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Femenino , Humanos , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Sistema de RegistrosRESUMEN
OBJECTIVES: Concern about falling is common among older hypertension patients and could impact decisions to intensify blood pressure therapy. Our aim was to determine whether intensive therapy targeting a systolic blood pressure (SBP) of 120 mm Hg is associated with greater changes in concern about falling when compared with standard therapy targeting an SBP of 140 mm Hg. DESIGN: Subsample analysis of participants randomized to either intensive or standard therapy in the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING: Approximately 100 outpatient sites. PARTICIPANTS: A total of 2313 enrollees in SPRINT; participants were all age 50 or older (mean = 69 y) and diagnosed with hypertension. MEASUREMENTS: Concern about falling was described by the shortened version of the Falls Efficacy Scale International as measured at baseline, 6 months, 1 year, and annually thereafter. RESULTS: Concern about falling showed a small but significant increase over time among all hypertension patients. No differences were noted, however, among those randomized to intensive vs standard therapy (P = .95). Among participants younger than 75 years, no increase in concern about falling over time was noted, but among participants aged 75 years and older, the mean falls self-efficacy score increased by .3 points per year (P < .0001). No differences were observed between the intensive and standard treatment groups when stratified by age (P = .55). CONCLUSION: Intensive blood pressure therapy is not associated with increased concern about falling among older hypertension patients healthy enough to participate in SPRINT. J Am Geriatr Soc 68:614-618, 2020.
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Accidentes por Caídas/estadística & datos numéricos , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , MasculinoRESUMEN
BACKGROUND: Patients with stage 1 systolic hypertension have increased risk of cardiovascular disease (CVD) events. METHODS: Using Cox models, we assess the effect of targeting an intensive SBP goal of less than 120âmmHg compared with standard SBP goal of less than 140âmmHg on the risk of CVD events in adults with stage 1 systolic hypertension with diabetes mellitus enrolled in Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) (nâ=â1901) and without diabetes mellitus enrolled in Systolic Blood Pressure Intervention Trial (SPRINT) (nâ=â3484) that used identical SBP goal interventions. OUTCOMES: In ACCORD BP, the primary composite CVD outcome was the first occurrence of myocardial infarction, stroke, or CVD mortality. In SPRINT, the primary composite CVD outcome was the first occurrence of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or CVD mortality. RESULTS: In SPRINT, targeting an intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.75 (95% confidence interval, 0.58-0.98); events 1.78 vs. 2.37%/year]. In ACCORD BP, the relationships of SBP goal with the primary CVD outcome was modified by the glycemia goal intervention (interaction Pâ=â0.039). In the standard glycemia subgroup (A1c target 7-7.9%), intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.61 (0.40-0.94); events 1.63 vs. 2.56%/year]. In the intensive glycemia subgroup (A1c target <6%), the risk of the primary CVD outcome was not significantly different between groups [hazard ratio 1.20 (0.76-1.89); events 1.91 vs. 1.60%/year]. CONCLUSION: Targeting an intensive SBP goal significantly reduced the risk of CVD events in patients with stage 1 systolic hypertension without diabetes and with diabetes on standard glycemia goal.
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Presión Sanguínea/fisiología , Enfermedades Cardiovasculares , Complicaciones de la Diabetes , Adulto , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Complicaciones de la Diabetes/complicaciones , Complicaciones de la Diabetes/epidemiología , Humanos , Factores de Riesgo , Sístole/fisiologíaRESUMEN
Resistant hypertension is a common medical problem. It carries a significantly increased risk of end-organ damage and cardiovascular events compared with more easily controlled hypertension. Resistant hypertension is most often related to isolated systolic hypertension and is characterized by aldosterone excess and increased intravascular volume. Its diagnosis requires the exclusion of pseudoresistance. The etiology of resistant hypertension is almost always multifactorial. Common reversible contributing factors need to be identified and addressed. Secondary causes of hypertension, such as primary aldosteronism, parenchymal and vascular kidney disease, and obstructive sleep apnea, require investigation and effective treatment if present. Therapy for resistant hypertension should be based on use of rational drug class combinations at optimal doses, with particular attention to adequate diuretic use. The addition of an aldosterone antagonist may further improve blood pressure control.
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Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/complicaciones , Presión Sanguínea , Resistencia a Medicamentos , Humanos , Hiperaldosteronismo/complicaciones , Hipertensión/epidemiología , Hipertensión/etiología , Fallo Renal Crónico/complicaciones , Estilo de Vida , Obesidad/complicaciones , Feocromocitoma/complicaciones , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/complicaciones , Prevalencia , Pronóstico , Obstrucción de la Arteria Renal/complicaciones , Factores de Riesgo , Apnea Obstructiva del Sueño/complicaciones , Insuficiencia del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Chronic kidney disease (CKD) has been associated with higher incidence of complications after total joint arthroplasty (TJA) but the incidence, risk factors and outcomes of acute kidney injury (AKI) in this setting remains insufficiently understood. METHODS: We assessed the impact of baseline CKD on the risk of developing AKI after TJA performed between 1/2012 and 12/2016 in a single-center, retrospective cohort study. CKD was defined by estimated glomerular filtration rate <60 mL/min/1.73 m2 on 2 separate occasions within 3 months prior TJA. AKI was defined using a modified Kidney Disease: Improving Global Outcomes criteria based on serum creatinine (sCr) only to assess the severity of AKI. Complete AKI recovery was defined as the lowest post-AKI sCr within 20% of pre-AKI sCr values and partial recovery if within 30%, all within 90 days after TJA. RESULTS: Twenty-four percent of the 1,212 subjects undergoing TJA had pre-existing CKD. The overall incidence of AKI in the CKD subjects was 30%; of these, 55% had stage-1 AKI, 1% had stage-2 AKI and 44% had stage-3 AKI. AKI was more common in African Americans, those with diabetes or heart failure, requiring perioperative transfusions or receiving diuretics before surgery. While 82% of the AKI subjects achieved complete recovery of kidney function, 4% had only partial recovery and 14% did not reach a post-AKI sCr level within 30% of pre-AKI values. The incidence (P < 0.001) but not the severity (Pâ¯=â¯0.202) of AKI correlated with stages of baseline CKD. CONCLUSIONS: The presence of CKD was associated with a high incidence of AKI after TJA. In these subjects, more than half the cases of AKI were of mild degree and had a favorable outcome. However, 18% of them did not have complete recovery of kidney function. Stages of baseline CKD were associated with increased incidence but not severity of AKI after TJA.
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Lesión Renal Aguda/etiología , Artroplastia de Reemplazo/efectos adversos , Insuficiencia Renal Crónica/cirugía , Lesión Renal Aguda/epidemiología , Anciano , Estudios de Cohortes , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Various definitions of acute kidney injury (AKI) exist, making comparisons among studies difficult. Despite this, significant changes have occurred in the epidemiology of AKI during the last decade. Recent studies, including PICARD and BEST, have examined the epidemiology of ICU-related AKI in the USA and worldwide, respectively, and found that AKI remains a major cause of morbidity and mortality. The incidence of AKI has increased, most likely due to a trend toward older, more severely and chronically ill patients admitted to the hospital. Sepsis and multi-organ system failure continue to be strongly associated with AKI, as well as pre-morbid chronic kidney disease. The proportion of patients with AKI requiring dialysis is high. The mortality of ICU-related AKI, although still very elevated, may be decreasing. Understanding these changes, in the context of standardized definitions, will be essential for the design of successful interventional studies.
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Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Ensayos Clínicos como Asunto , Medición de Riesgo/métodos , Lesión Renal Aguda/clasificación , Humanos , Internacionalidad , Prevalencia , Factores de Riesgo , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction (P=0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Bloqueadores de los Canales de Calcio/uso terapéutico , Manejo de la Enfermedad , Diuréticos/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Determinación de la Presión Sanguínea , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sístole , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: To determine if the effects of intensive lowering of systolic blood pressure (goal of less than 120âmmHg) versus standard lowering (goal of less than 140âmmHg) upon cardiovascular, renal, and safety outcomes differed by gender. METHODS: Nine thousand three hundred and sixty-one men and women aged 50 years or older with systolic blood pressure of 130âmmHg or greater, taking 0-4 antihypertensive medications, and with increased risk of cardiovascular disease, but free of diabetes, were randomly assigned to either a systolic blood pressure target of less than 120âmmHg (intensive treatment) or a target of less than 140âmmHg (standard treatment). The primary composite outcome encompassed incident myocardial infarction, heart failure, other acute coronary syndromes, stroke, or cardiovascular-related death. All-cause mortality, renal outcomes, and serious adverse events were also assessed. RESULTS: Compared with the standard treatment group, the primary composite outcome in the intensive treatment group was reduced by 16% [hazard ratio 0.84 (0.61-1.13)] in women, and by 27% in men [hazard ratio 0.73 (0.59-0.89), P value for interaction between treatment and gender is 0.45]. Similarly, the effect of the intensive treatment on individual components of the primary composite outcome, renal outcomes, and overall serious adverse events was not significantly different according to gender. CONCLUSION: In adults with hypertension but not with diabetes, treatment to a systolic blood pressure goal of less than 120âmmHg, compared with a goal of less than 140âmmHg, resulted in no heterogeneity of effect between men and women on cardiovascular or renal outcomes, or on rates of serious adverse events.ClinicalTrials.gov number, NCT01206062.
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Antihipertensivos/uso terapéutico , Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Síndrome Coronario Agudo/epidemiología , Anciano , Enfermedades Cardiovasculares/mortalidad , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Incidencia , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Planificación de Atención al Paciente , Modelos de Riesgos Proporcionales , Factores Sexuales , Accidente Cerebrovascular/epidemiología , Sístole , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. METHODS: We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. RESULTS: Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57-0.86), 0.71 (0.51-0.98), 0.62 (0.33-1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29-0.81), 0.77 (0.37-1.57), and 0.17 (0.01-1.08). All-cause mortality HRs were 0.61 (0.47-0.80), 0.92 (0.63-1.35), and 1.58 (0.73-3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. CONCLUSION: Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications. CLINICAL TRIALS REGISTRATION: Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.
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Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/etiología , Anciano , Anciano de 80 o más Años , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Población Negra , Etnicidad , Femenino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Hispánicos o Latinos , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Grupos Raciales , Factores Socioeconómicos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Sístole , Resultado del Tratamiento , Población BlancaRESUMEN
Orthostatic changes in systolic blood pressure (SBP) impact cardiovascular outcomes. In this study, we aimed to determine the pattern of orthostatic systolic pressure changes in participants enrolled in the SBP Intervention Trial (SPRINT) at their baseline visit before randomization and sought to understand clinical factors predictive of these changes. Of the 9323 participants enrolled in SPRINT, 8662 had complete data for these analyses. The SBP after 1 minute of standing was subtracted from the mean value of the three preceding seated SBP values. At the baseline visit, medical history, medications, anthropometric measures, and standard laboratory testing were undertaken. The mean age of SPRINT participants was 68 years, two-thirds were male, with 30% black, 11% Hispanic, and 55% Caucasian. The spectrum of SBP changes on standing demonstrated that increases in SBP were as common as declines, and about 5% of participants had an increase, and 5% had a decrease of >20 mm Hg in SBP upon standing. Female sex, taller height, more advanced kidney disease, current smoking, and several drug classes were associated with larger declines in BP upon standing, while black race, higher blood levels of glucose and sodium, and heavier weight were associated with more positive values of the change in BP upon standing. Our cross-sectional results show a significant spectrum of orthostatic SBP changes, reflecting known (eg, age) and less well-known (eg, kidney function) relationships that may be important considerations in determining the optimal target blood pressure in long-term outcomes of older hypertensive patients.
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Presión Sanguínea/fisiología , Tasa de Filtración Glomerular , Hipertensión/complicaciones , Hipotensión Ortostática/fisiopatología , Postura/fisiología , Insuficiencia Renal Crónica/complicaciones , Factores de Edad , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Determinación de la Presión Sanguínea , Estatura , Estudios Transversales , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipotensión Ortostática/complicaciones , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , SístoleRESUMEN
BACKGROUND: Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria. METHODS AND RESULTS: In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients. CONCLUSIONS: In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Hipercolesterolemia/tratamiento farmacológico , Enfermedades Renales/tratamiento farmacológico , Lisinopril/farmacología , Proteinuria/tratamiento farmacológico , Adolescente , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/farmacología , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Enfermedad Crónica , Diuréticos/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Hipercolesterolemia/complicaciones , Hipoalbuminemia/sangre , Hipoalbuminemia/complicaciones , Hipoalbuminemia/tratamiento farmacológico , Hipotensión/inducido químicamente , Enfermedades Renales/complicaciones , Enfermedades Renales/fisiopatología , Pruebas de Función Renal , Lisinopril/administración & dosificación , Lisinopril/efectos adversos , Estudios Longitudinales , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Proteinuria/etiología , Sodio en la Dieta , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
Refractory hypertension is an extreme phenotype of treatment failure defined as uncontrolled blood pressure in spite of ≥5 classes of antihypertensive agents, including chlorthalidone and a mineralocorticoid receptor antagonist. A prospective evaluation of possible mechanisms of refractory hypertension has not been done. The goal of this study was to test for evidence of heightened sympathetic tone as indicated by 24-hour urinary normetanephrine levels, clinic and ambulatory heart rate (HR), HR variability, arterial stiffness as indexed by pulse wave velocity, and systemic vascular resistance compared with patients with controlled resistant hypertension. Forty-four consecutive patients, 15 with refractory and 29 with controlled resistant hypertension, were evaluated prospectively. Refractory hypertensive patients were younger (48±13.3 versus 56.5±14.1 years; P=0.038) and more likely women (80.0 versus 51.9%; P=0.047) compared with patients with controlled resistant hypertension. They also had higher urinary normetanephrine levels (464.4±250.2 versus 309.8±147.6 µg per 24 hours; P=0.03), higher clinic HR (77.8±7.7 versus 68.8±7.6 bpm; P=0.001) and 24-hour ambulatory HR (77.8±7.7 versus 68.8±7.6; P=0.0018), higher pulse wave velocity (11.8±2.2 versus 9.4±1.5 m/s; P=0.009), reduced HR variability (4.48 versus 6.11; P=0.03), and higher systemic vascular resistance (3795±1753 versus 2382±349 dyne·s·cm(5)·m(2); P=0.008). These findings are consistent with heightened sympathetic tone being a major contributor to antihypertensive treatment failure and highlight the need for effective sympatholytic therapies in patients with refractory hypertension.
Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Adulto , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Cardiografía de Impedancia , Quimioterapia Combinada , Femenino , Frecuencia Cardíaca , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/orina , Masculino , Persona de Mediana Edad , Normetanefrina/orina , Estudios Prospectivos , Análisis de la Onda del Pulso , Insuficiencia del Tratamiento , Resistencia Vascular , Rigidez VascularRESUMEN
Drugs that inhibit the renin-angiotensin system (RAS) are of proven benefit in the treatment of hypertension, congestive heart failure, or acute myocardial infarction. In the last decade, several clinical trials have shown that RAS inhibitors also offer significant renoprotection in both diabetic and non-diabetic nephropathy. However, patients with advanced renal insufficiency did not take part in these trials because of the risk of acute renal failure (ARF) and hyperkalemia, and, for the same reason, most physicians do not offer these drugs to patients with impaired renal function. Recently, a post-hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) study which included patients with severe renal insufficiency, showed that RAS inhibition slows glomerular filtration rate (GFR) decline over time and progression to end-stage renal disease (ESRD) in a safe way in patients quite close to ESRD (basal GFR, 10 to 30 ml/min/1.73m2). These beneficial effects have also been shown in the Reduction of Endpoints in NIDDM with the All Antagonist Losartan (RENAAL) study, in patients with type 2 diabetes mellitus, clinical proteinuria, and renal insufficiency, where RAS inhibition therapy significantly reduced the risk of ESRD once doubling of baseline serum creatinine levels had been achieved as compared to non-RAS anti-hypertensive treatment. Thus, these data suggest that RAS inhibition therapy should be given to all patients with proteinuric chronic nephropathy, independently of the level of renal function.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Tasa de Filtración Glomerular/efectos de los fármacos , Fallo Renal Crónico/tratamiento farmacológico , Ramipril/uso terapéutico , Sistema Renina-Angiotensina/efectos de los fármacos , Ensayos Clínicos Controlados como Asunto , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/diagnóstico , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Masculino , Pronóstico , Sistema Renina-Angiotensina/fisiología , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The morning blood pressure surge (MBPS) has been shown to be an independent predictor of cardiovascular events. There is insufficient evidence on the effect of nebivolol, a vasodilating ß1-receptor blocker, on the MBPS when given in the morning or the evening. This is a prospective, randomized, double-blind, crossover study designed to test morning vs. evening dosing of nebivolol in nondiabetic, hypertensive patients. Patients received nebivolol 5 mg/day (force-titrated to 10 mg/day after 1 week) in the morning or evening and corresponding placebos. Patients underwent ambulatory BP monitoring at baseline and after each treatment phase. Forty-two patients were randomized, of whom 38 completed both study periods. Both morning and evening dosed nebivolol significantly lowered daytime, nighttime, and 24-hour BP after 3 weeks of treatment. Evening (but not morning) dosing significantly reduced prewaking systolic BP from baseline (8.64 ± 26.46 mm Hg, P = .048). Nebivolol given in the morning or the evening significantly reduces 24-hour BP parameters. Evening dosed nebivolol may confer some advantage over morning dosing in reducing prewaking systolic BP.