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1.
Am J Kidney Dis ; 76(6): 765-774, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32682697

RESUMO

RATIONALE & OBJECTIVE: In prior research and in practice, the difference between estimated glomerular filtration rate (eGFR) calculated from cystatin C level and eGFR calculated from creatinine level has not been assessed for clinical significance and relevance. We evaluated whether these differences contain important information about frailty. STUDY DESIGN: A cohort analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9,092 hypertensive SPRINT participants who had baseline measurements of serum creatinine, cystatin C, and frailty. EXPOSURE: eGFRs calculated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (eGFRcys and eGFRcr), and eGFRDiff, calculated as eGFRcys-eGFRcr. OUTCOMES: A validated 35-item frailty index that included questionnaire data for general and physical health, limitations of activities, pain, depression, sleep, energy level, self-care, and smoking status, as well as medical history, cognitive assessment, and laboratory data. We defined frailty as frailty index score>0.21 (range, 0-1). The incidence of injurious falls, hospitalizations, cardiovascular events, and mortality was also recorded. ANALYTICAL APPROACH: We used logistic regression to model the cross-sectional association of baseline eGFRDiff with frailty among all SPRINT participants. Adjusted proportional hazards regression was used to evaluate the association of eGFRDiff with adverse outcomes and mortality. RESULTS: Mean age was 68±9 (SD) years, mean eGFRcys and eGFRcr were 73±23 and 72±20mL/min/1.73m2, and mean eGFRDiff was 0.5±15mL/min/1.73m2. In adjusted models, each 1-SD higher eGFRDiff was associated with 24% lower odds of prevalent frailty (OR, 0.76; 95% CI, 0.71-0.81), as well as with lower incidence rate of injurious falls (HR, 0.84; 95% CI, 0.77-0.92), hospitalization (HR, 0.91; 95% CI, 0.88-0.95), cardiovascular events (HR, 0.89; 95% CI, 0.81-0.97), and all-cause mortality (HR, 0.71; 95% CI, 0.63-0.82); P<0.01. LIMITATIONS: Gold-standard measure of kidney function and assessment of muscle mass were not available. CONCLUSIONS: The difference between eGFRcys and eGFRcr is associated with frailty and health status. Positive eGFRDiff is strongly associated with lower risks for longitudinal adverse outcomes and mortality, even after adjusting for chronic kidney disease stage and baseline frailty.


Assuntos
Pressão Sanguínea/fisiologia , Creatinina/sangue , Cistatina C/sangue , Fragilidade/sangue , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/sangue , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Fragilidade/complicações , Humanos , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Sístole
2.
Eur Heart J ; 40(42): 3486-3493, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257404

RESUMO

AIMS: Biomarkers of kidney tubule injury, inflammation and fibrosis have been studied extensively and established as risk markers of adverse kidney and cardiovascular disease (CVD) outcomes. However, associations of markers of kidney tubular function with adverse clinical events have not been well studied, especially in persons with chronic kidney disease (CKD). METHODS AND RESULTS: Using a sample of 2377 persons with CKD at the baseline Systolic Blood Pressure Intervention Trial (SPRINT) visit, we evaluated the association of three urine tubular function markers, alpha-1 microglobulin (α1m), beta-2 microglobulin (ß2m), and uromodulin, with a composite CVD endpoint (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes) and mortality using Cox proportional hazards regression, adjusted for baseline estimated glomerular filtration rate (eGFR), albuminuria, and CVD risk factors. In unadjusted analysis, over a median follow-up of 3.8 years, α1m and ß2m had positive associations with composite CVD events and mortality, whereas uromodulin had an inverse association with risk for both outcomes. In multivariable analysis including eGFR and albuminuria, a two-fold higher baseline concentration of α1m was associated with higher risk of CVD [hazard ratio (HR) 1.25; 95% confidence interval (CI): 1.10-1.45] and mortality (HR 1.25; 95% CI: 1.10-1.46), whereas ß2m had no association with either outcome. A two-fold higher uromodulin concentration was associated with lower CVD risk (HR 0.79; 95% CI: 0.68-0.90) but not mortality (HR 0.86; 95% CI: 0.73-1.01) after adjusting for similar confounders. CONCLUSION: Among non-diabetic persons with CKD, biomarkers of tubular function are associated with CVD events and mortality independent of glomerular function and albuminuria.


Assuntos
Doenças Cardiovasculares , Túbulos Renais/fisiologia , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Pressão Sanguínea , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Feminino , Taxa de Filtração Glomerular , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Uromodulina/urina
3.
Am J Kidney Dis ; 71(3): 352-361, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29162340

RESUMO

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.


Assuntos
Injúria Renal Aguda/prevenção & controle , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Injúria Renal Aguda/etiologia , Idoso , Determinação da Pressão Arterial , Cuidados Críticos/métodos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Padrões de Referência , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
4.
Clin Nephrol ; 90(4): 296-301, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106368

RESUMO

Adenine phosphoribosyltransferase (APRT) deficiency (OMIM #614723) is a rare autosomal recessive defect in the purine salvage pathway that causes excessive production of 2,8-dihydroxyadenine, leading to nephrolithiasis and chronic kidney disease (CKD). This case report describes the natural history of CKD in untreated APRT deficiency. We describe a novel APRT mutation (chr16:88877985 G / C; c.195 C>/G; p.His54Asp) presenting with CKD without nephrolithiasis. The patient initially required dialysis, but kidney function improved with allopurinol. We reviewed APRT deficiency reported in the literature to determine the loss of kidney function in individuals with untreated APRT deficiency and its relationship to nephrolithiasis. We identified 95 individuals in whom kidney function was assessed prior to treatment. There was a bimodal distribution of kidney failure. AKI occurred frequently in childhood due to obstructing nephrolithiasis or crystalline nephropathy and was usually reversible. CKD developed after age 20 in all patients irrespective of nephrolithiasis history, with 36/42 patients > 40 years of age having at least stage 3 CKD, and 24/42 having an eGFR > 10 mL/min/1.73m2 or being on dialysis. There were 13 adults without nephrolithiasis and 50 adults with nephrolithiasis. The mean age of end-stage renal diesease (ESRD) was 50.52 ± 13.9 for those without nephrolithiasis and 43.4 ± 15.8 years for those with nephrolithiasis (p = 0.24). APRT deficiency is associated with slowly progressive CKD that occurs independently of nephrolithiasis. Diagnosis should be considered in all individuals with chronic tubulointerstitial kidney disease, with or without the presence of nephrolithiasis. In our patient, allopurinol 300 mg/day resulted in improvement of kidney function.
.


Assuntos
Adenina Fosforribosiltransferase/deficiência , Cálculos Renais/etiologia , Erros Inatos do Metabolismo/complicações , Nefrite Intersticial/etiologia , Insuficiência Renal Crônica/etiologia , Urolitíase/complicações , Alopurinol/uso terapêutico , Antimetabólitos/uso terapêutico , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/complicações
5.
Ann Intern Med ; 167(6): 375-383, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28869987

RESUMO

BACKGROUND: The public health significance of the reported higher incidence of chronic kidney disease (CKD) with intensive systolic blood pressure (SBP) lowering is unclear. OBJECTIVE: To examine the effects of intensive SBP lowering on kidney and cardiovascular outcomes and contrast its apparent beneficial and adverse effects. DESIGN: Subgroup analyses of SPRINT (Systolic Blood Pressure Intervention Trial). (ClinicalTrials.gov: NCT01206062). SETTING: Adults with high blood pressure and elevated cardiovascular risk. PARTICIPANTS: 6662 participants with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2. INTERVENTION: Random assignment to an intensive or standard SBP goal (120 or 140 mm Hg, respectively). MEASUREMENTS: Differences in mean eGFR during follow-up (estimated with a linear mixed-effects model), prespecified incident CKD (defined as a >30% decrease in eGFR to a value <60 mL/min/1.73 m2), and a composite of all-cause death or cardiovascular event, with surveillance every 3 months. RESULTS: The difference in adjusted mean eGFR between the intensive and standard groups was -3.32 mL/min/1.73 m2 (95% CI, -3.90 to -2.74 mL/min/1.73 m2) at 6 months, was -4.50 mL/min/1.73 m2 (CI, -5.16 to -3.85 mL/min/1.73 m2) at 18 months, and remained relatively stable thereafter. An incident CKD event occurred in 3.7% of participants in the intensive group and 1.0% in the standard group at 3-year follow-up, with a hazard ratio of 3.54 (CI, 2.50 to 5.02). The corresponding percentages for the composite of death or cardiovascular event were 4.9% and 7.1% at 3-year follow-up, with a hazard ratio of 0.71 (CI, 0.59 to 0.86). LIMITATION: Long-term data were lacking. CONCLUSION: Intensive SBP lowering increased risk for incident CKD events, but this was outweighed by cardiovascular and all-cause mortality benefits. PRIMARY FUNDING SOURCE: National Institutes of Health.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Incidência , Insuficiência Renal Crônica/etiologia , Fatores de Risco
6.
J Am Soc Nephrol ; 28(9): 2812-2823, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28642330

RESUMO

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.


Assuntos
Pressão Sanguínea , Causas de Morte , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Síndrome Coronariana Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Feminino , Seguimentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Insuficiência Renal Crônica/complicações , Acidente Vascular Cerebral/epidemiologia , Sístole
7.
Nitric Oxide ; 69: 78-90, 2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-28549665

RESUMO

Aerobic exercise training is an effective therapy to improve peak aerobic power (peak VO2) in individuals with hypertension (HTN, AHA/ACC class A) and heart failure patients with preserved ejection fraction (HFpEF). High nitrate containing beetroot juice (BRJ) also improves sub-maximal endurance and decreases blood pressure in both HTN and HFpEF. We hypothesized that combining an aerobic exercise and dietary nitrate intervention would result in additive or even synergistic positive effects on exercise tolerance and blood pressure in HTN or HFpEF. We report results from two pilot studies examining the effects of supervised aerobic exercise combined with dietary nitrate in patients with controlled HTN (n = 26, average age 65 ± 5 years) and in patients with HFpEF (n = 20, average age 69 ± 7 years). All patients underwent an aerobic exercise training regimen; half were randomly assigned to consume a high nitrate-containing beet juice beverage (BRJ containing 6.1 mmol nitrate for the HFpEF study consumed three times a week and 8 mmol nitrate for the HTN study consumed daily) while the other half consumed a beet juice beverage with the nitrate removed (placebo). The main result was that there was no added benefit observed for any outcomes when comparing BRJ to placebo in either HTN or HFpEF patients undergoing exercise training (p ≥ 0.14). There were within-group benefits. In the pilot study in patients with HFpEF, aerobic endurance (primary outcome), defined as the exercise time to volitional exhaustion during submaximal cycling at 75% of maximal power output, improved during exercise training within each group from baseline to end of study, 369 ± 149 s vs 520 ± 257 s (p = 0.04) for the placebo group and 384 ± 129 s vs 483 ± 258 s for the BRJ group (p = 0.15). Resting systolic blood pressure in patients with HFpEF also improved during exercise training in both groups, 136 ± 16 mm Hg vs 122 ± 3 mm Hg for the placebo group (p < 0.05) and 132 ± 12 mm Hg vs 119 ± 9 mm Hg for the BRJ group (p < 0.05). In the HTN pilot study, during a treadmill graded exercise test, peak oxygen consumption (primary outcome) did not change significantly, but time to exhaustion (also a primary outcome) improved in both groups, 504 ± 32 s vs 601 ± 38 s (p < 0.05) for the placebo group and 690 ± 38 s vs 772 ± 95 s for the BRJ group (p < 0.05) which was associated with a reduction in supine resting systolic blood pressure in BRJ group. Arterial compliance also improved during aerobic exercise training in both the HFpEF and the HTN patients for both BRJ and placebo groups. Future work is needed to determine if larger nitrate doses would provide an added benefit to supervised aerobic exercise in HTN and HFpEF patients.


Assuntos
Suplementos Nutricionais , Exercício Físico , Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Nitratos/administração & dosagem , Idoso , Beta vulgaris , Pressão Sanguínea/efeitos dos fármacos , Feminino , Sucos de Frutas e Vegetais , Humanos , Pessoa de Meia-Idade , Nitratos/sangue , Nitritos/sangue , Oxigênio/sangue , Resistência Física/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos
8.
Kidney Int ; 90(2): 440-449, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27342958

RESUMO

To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (ß = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (ß = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (ß= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (ß/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease.


Assuntos
Apolipoproteínas/genética , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Substância Cinzenta/anatomia & histologia , Nefropatias/genética , Lipoproteínas HDL/genética , Substância Branca/anatomia & histologia , Negro ou Afro-Americano/genética , Apolipoproteína L1 , Pressão Sanguínea , Encéfalo/irrigação sanguínea , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Doenças de Pequenos Vasos Cerebrais/genética , Cognição , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Taxa de Filtração Glomerular , Substância Cinzenta/diagnóstico por imagem , Humanos , Hipertensão/epidemiologia , Nefropatias/complicações , Testes de Função Renal , Imageamento por Ressonância Magnética , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Substância Branca/diagnóstico por imagem
9.
Am J Nephrol ; 44(2): 130-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27513312

RESUMO

BACKGROUND: Interventional trials have used either the Modification of Diet in Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation for determination of estimated glomerular filtration rate (eGFR) to define whether participants have stages 3-5 CKD. The equation used to calculate eGFR may influence the number and characteristics of participants designated as having CKD. METHODS: We examined the classification of CKD at baseline using both equations in the Systolic Blood Pressure Intervention Trial (SPRINT). eGFR was calculated at baseline using fasting serum creatinine values from a central laboratory. RESULTS: Among 9,308 participants with baseline CKD classification using the 4-variable MDRD equation specified in the SPRINT protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage (higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage (lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90 ml/min/1.73 m2, participants <75 years were more likely to be reclassified to a less advanced CKD stage; this reclassification was more likely to occur in non-blacks rather than blacks. Participants aged ≥75 years were more likely to be reclassified to a more advanced than a less advanced CKD stage, regardless of baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73 m2) occurred in 3% of participants. CONCLUSIONS: Use of the MDRD equation led to a higher percentage of participants being classified as having CKD stages 3-4. Younger and non-black participants were more likely to be reclassified as not having CKD using the CKD-EPI equation.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/dietoterapia , Fatores Etários , Idoso , Determinação da Pressão Arterial , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
JAMA ; 315(24): 2673-82, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27195814

RESUMO

IMPORTANCE: The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. OBJECTIVE: To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. INTERVENTIONS: Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). MAIN OUTCOMES AND MEASURES: The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. RESULTS: Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). CONCLUSIONS AND RELEVANCE: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206062.


Assuntos
Síndrome Coronariana Aguda/mortalidade , Anti-Hipertensivos/uso terapêutico , Insuficiência Cardíaca/mortalidade , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial , Causas de Morte , Feminino , Humanos , Hipertensão/complicações , Masculino
11.
Kidney Int ; 87(1): 169-75, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25029429

RESUMO

Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (ß) 0.33) and negatively associated with eGFR (ß -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g.


Assuntos
Apolipoproteínas/genética , Doenças Cardiovasculares/genética , Lipoproteínas HDL/genética , Insuficiência Renal Crônica/genética , Negro ou Afro-Americano/genética , Apolipoproteína L1 , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade
12.
Am J Kidney Dis ; 61(5): 828-31, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23391537

RESUMO

Dysfunction of the alternative pathway of complement activation provides a pathophysiologic link between the C3 glomerulopathies dense deposit disease and glomerulonephritis with C3 deposition and the clinically and histologically distinct atypical hemolytic uremic syndrome. Previously, dense deposit disease was known as membranoproliferative glomerulonephritis type II, but paucity or complete lack of immunoglobulin deposition on immunofluorescence staining and advances in our understanding of alternative pathway dysregulation have separated it from immune complex-mediated membranoproliferative glomerulonephritis types I and III. We discuss a case of dense deposit disease and review the current pathologic classification, clinical course, treatment options, and related conditions.


Assuntos
Complemento C3/metabolismo , Via Alternativa do Complemento/imunologia , Glomerulonefrite Membranoproliferativa/imunologia , Glomérulos Renais/ultraestrutura , Adolescente , Complexo Antígeno-Anticorpo/imunologia , Biópsia , Complemento C3/imunologia , Glomerulonefrite Membranoproliferativa/metabolismo , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Glomérulos Renais/imunologia , Masculino , Microscopia Eletrônica , Microscopia de Fluorescência
13.
Hypertension ; 79(9): 2071-2080, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35766041

RESUMO

BACKGROUND: The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated reductions in major cardiovascular disease events and mortality with an intensive systolic blood pressure (SBP) goal intervention. However, a detailed description of the blood pressure intervention, antihypertensive medication usage, blood pressure levels, and rates and predictors of blood pressure control has not been reported previously. METHODS: Hypertensive participants (n=9361) 50 years and older with elevated cardiovascular disease risk were randomized 1:1 to SBP goal <120 mm Hg or SBP goal <140 mm Hg. Guideline-recommended antihypertensive medications and dosing were provided at no cost. Intensive group participants were started on at least 2 medications, and medications were adjusted monthly until SBP goal was achieved, if feasible. Standard group participants were treated to achieve SBP 135 to 139 mm Hg. RESULTS: Baseline blood pressure (median±interquartile range) was 138±19/78±16 mm Hg. For intensive group participants, percent at goal rose from 8.9% at baseline to 52.4% at 6 months and average antihypertensive medications rose from 2.2 to 2.7; SBP was <120 mm Hg in 61.6% and <130 mm Hg in 80.0% at their final visit. For the standard group participants, percent at goal rose from 53.0% at baseline to 68.6% at 6 months, while antihypertensive medications fell from 1.9 to 1.8. From 6 to 36 months, median SBP was stable at 119±14 mm Hg for intensive and 136±15 mm Hg for standard participants, with stable numbers of medications. Few predictors of SBP control were found in multiple regression models. CONCLUSIONS: These results may inform and help replicate the benefits of SPRINT in clinical practice. REGISTRATION: URL: http://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.


Assuntos
Doenças Cardiovasculares , Hipertensão , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Fatores de Risco , Resultado do Tratamento
14.
Hypertension ; 76(6): 1717-1724, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33100049

RESUMO

Intensive blood pressure control decreases the rate of cardiovascular events by >25% compared with standard blood pressure control. We sought to determine whether the decrease in cardiovascular events seen with intensive blood pressure control is associated with an increased rate of other causes of hospitalization. This is a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) in 9361 adult participants with hypertension and elevated cardiovascular risk. Participants were randomly assigned to an intensive or standard systolic blood pressure goal (<120 or <140 mm Hg, respectively). The primary outcome was hospitalization rates per 100 person-years for hospitalizations not associated with SPRINT primary events. After excluding hospitalizations linked to SPRINT primary events, there were 4678 participants with a rate of 19.70 hospitalizations per 100 person-years, compared with 4683 participants with a rate of 19.65 (P=0.37). Equivalence testing shows that these hospitalization rates were statistically equivalent at the P=0.05 level. Of those with hospitalizations, >1 hospitalization was seen in 38.8% of intensive arm participants and 41.9% of standard arm participants (P=0.08). The mean cumulative count of nonprimary event hospitalizations was comparable between the two arms. The most common causes of hospitalization were cardiovascular (23.6%) followed by injuries, including bone and joint therapeutic procedures (15.7%), infections (12.0%), and nervous systems disorders (10.7%). No categories of hospitalization were statistically more common in the intensive arm compared with the standard arm. Thus, the decrease in cardiovascular events seen with intensive blood pressure control is not associated with an increased rate of other causes of hospitalization. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hospitalização/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Idoso , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
15.
Clin J Am Soc Nephrol ; 15(8): 1121-1128, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669306

RESUMO

BACKGROUND AND OBJECTIVES: It is unclear whether the presence of albuminuria modifies the effects of intensive systolic BP control on risk of eGFR decline, cardiovascular events, or mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Systolic Blood Pressure Intervention Trial randomized nondiabetic adults ≥50 years of age at high cardiovascular risk to a systolic BP target of <120 or <140 mm Hg, measured by automated office BP. We compared the absolute risk differences and hazard ratios of ≥40% eGFR decline, the Systolic Blood Pressure Intervention Trial primary cardiovascular composite outcome, and all-cause death in those with or without baseline albuminuria (urine albumin-creatinine ratio ≥30 mg/g). RESULTS: Over a median follow-up of 3.1 years, 69 of 1723 (4%) participants with baseline albuminuria developed ≥40% eGFR decline compared with 61 of 7162 (1%) participants without albuminuria. Incidence rates of ≥40% eGFR decline were higher in participants with albuminuria (intensive, 1.74 per 100 person-years; standard, 1.17 per 100 person-years) than in participants without albuminuria (intensive, 0.48 per 100 person-years; standard, 0.11 per 100 person-years). Although effects of intensive BP lowering on ≥40% eGFR decline varied by albuminuria on the relative scale (hazard ratio, 1.48; 95% confidence interval, 0.91 to 2.39 for albumin-creatinine ratio ≥30 mg/g; hazard ratio, 4.55; 95% confidence interval, 2.37 to 8.75 for albumin-creatinine ratio <30 mg/g; P value for interaction <0.001), the absolute increase in ≥40% eGFR decline did not differ by baseline albuminuria (incidence difference, 0.38 events per 100 person-years for albumin-creatinine ratio ≥30 mg/g; incidence difference, 0.58 events per 100 person-years for albumin-creatinine ratio <30 mg/g; P value for interaction =0.60). Albuminuria did not significantly modify the beneficial effects of intensive systolic BP lowering on cardiovascular events or mortality evaluated on relative or absolute scales. CONCLUSIONS: Albuminuria did not modify the absolute benefits and risks of intensive systolic BP lowering.


Assuntos
Albuminúria/epidemiologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Taxa de Filtração Glomerular , Hipertensão/tratamento farmacológico , Nefropatias/epidemiologia , Rim/fisiopatologia , Idoso , Albuminúria/diagnóstico , Albuminúria/mortalidade , Albuminúria/fisiopatologia , Anti-Hipertensivos/efeitos adversos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Incidência , Nefropatias/diagnóstico , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
16.
Kidney Int Rep ; 2(4): 713-720, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28758155

RESUMO

INTRODUCTION: Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, 2,568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including non-fatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, non-fatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality. METHODS: Cox proportional hazards regression models were employed adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg versus <140 mm Hg). RESULTS: Fourteen percent of participants had two APOL1 RRVs; these individuals also had lower baseline estimated GFR and higher levels of albuminuria and BMI. After a median follow-up of 39 months, no significant association was observed between APOL1 RRVs and the primary composite CVD outcome, any of its components, or all-cause mortality (recessive or additive genetic models). APOL1 demonstrated a trend toward association with sustained 30% reduction in estimated GFR to <60 ml/min/1.73m2 in those with normal kidney function at baseline (hazard ratio [95% CI] 1.64 [0.85-2.93]; p=0.114, recessive model). CONCLUSION: APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, non-diabetic African American participants in SPRINT.

17.
Crit Rev Oncol Hematol ; 59(3): 250-5, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16527489

RESUMO

Use of adjuvant chemotherapy for breast cancer decreases with increasing age. We examined the effect of comorbidity on adjuvant chemotherapy use in older women (age >55 years) in a tertiary care Oncology Clinic. Clinic charts of new, early stage breast cancer patients over age 55 were reviewed. Multivariate analysis was used to determine the effect of age (55-64 versus > or =65 years), tumor stage, and comorbidity (Charlson score) on management. Two hundred and seventy-three charts were reviewed. Older women had a greater mean Charlson comorbidity score (0.72 versus 0.21; p<0.001). Tamoxifen use was similar in both groups (82.8% versus 81.1%, p=0.72). Chemotherapy was less frequently used in older women, regardless of nodal status: overall, 13.1% versus 45.6%, p<0.001; node-negative, 8.2% versus 32.1%, p<0.001; and node-positive, 25% versus 83.8%, p<0.001. In a multivariate analysis, lower stage, older age, and higher comorbidity were predictive of less frequent use of adjuvant chemotherapy. Though higher comorbidity was associated with less use of adjuvant chemotherapy, it did not totally account for the low use of chemotherapy in older compared to younger women. More work should be planned to dissect out specific reasons for differences in treatment by age.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Planejamento de Assistência ao Paciente/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Estudos Retrospectivos
18.
Hypertension ; 59(3): 740-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22311907

RESUMO

Imbalances in circulating angiogenic factors contribute to the pathogenesis of preeclampsia. To characterize levels of angiogenic factors in pregnant women with chronic hypertension, we prospectively followed 109 women and measured soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor at 12, 20, 28, and 36 weeks' gestation and postpartum. Superimposed preeclampsia developed in 37 (34%) and was early onset (<34 weeks) in 9 and later onset (≥34 weeks) in 28. Circulating levels of sFlt1 and the ratio of sFlt1 to placental growth factor were higher before clinical diagnosis at 20 weeks' gestation in women who subsequently developed early onset preeclampsia between 28 and 34 weeks compared with levels in women who never developed preeclampsia (P=0.001) or who developed late-onset preeclampsia (P=0.001). Circulating levels of sFlt1, soluble endoglin, and the ratio of sFlt1:placental growth factor were also significantly higher, and placental growth factor levels were significantly lower at the time of clinical diagnosis of superimposed preeclampsia in women with either early or late-onset superimposed preeclampsia compared with levels at similar gestational ages in those with uncomplicated chronic hypertension. We conclude that alterations in angiogenic factors are detectable before and at the time of clinical diagnosis of early onset superimposed preeclampsia, whereas alterations were observed only at the time of diagnosis in women with late-onset superimposed preeclampsia. Longitudinal measurements of angiogenic factors may help anticipate early onset superimposed preeclampsia and facilitate diagnosis of superimposed preeclampsia in women with chronic hypertension.


Assuntos
Indutores da Angiogênese/sangue , Pressão Sanguínea/fisiologia , Carbonato de Cálcio/administração & dosagem , Hipertensão/sangue , Pré-Eclâmpsia/sangue , Adulto , Antiácidos/administração & dosagem , Biomarcadores/sangue , Doença Crônica , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Idade Gestacional , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Resultado do Tratamento
19.
Ther Adv Cardiovasc Dis ; 3(1): 65-73, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19124387

RESUMO

Pre-eclampsia is the second leading cause of maternal morbidity and mortality in the United States. Infants born to affected mothers face a five-fold increase in death rate [Lain and Roberts 2002; National Heart Lung and Blood Institute 2001]. Although pre-eclampsia has been recognized by physicians for millennia, relatively little is known about its pathogenesis or prevention. Predicting its development is often extremely difficult, perhaps leading the Greeks to use the name 'eklampsis' meaning lightening. Recent studies provide novel insights into the role of the placenta in the development of pre-eclampsia and demonstrate novel markers to assist in predicting the onset of disease and potential therapeutic targets. Following an introduction which highlights the classification of hypertensive disorders of pregnancy and defines incidence and adverse outcomes of pre-eclampsia, this manuscript will discuss the role of the placenta in the pathophysiology of pre-eclampsia and recent markers that may predict its onset.


Assuntos
Biomarcadores/sangue , Placenta/fisiopatologia , Placentação , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/fisiopatologia , Proteínas Angiogênicas/sangue , Antígenos CD/sangue , Autoanticorpos/sangue , Proteína C-Reativa/metabolismo , Diagnóstico Precoce , Endoglina , Feminino , Galectinas/sangue , Humanos , Incidência , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Valor Preditivo dos Testes , Gravidez , Proteínas da Gravidez/sangue , Receptores de Superfície Celular/sangue , Componente Amiloide P Sérico/metabolismo
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