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1.
J Hum Hypertens ; 33(10): 735-740, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30804464

RESUMO

We examined the association of orthostatic hypertension with all-cause mortality in the active treatment and placebo randomized groups of the Systolic Hypertension in the Elderly Program (SHEP). SHEP was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the effect of chlorthalidone-based antihypertensive treatment on the rate of occurrence of stroke among older persons with isolated systolic hypertension (ISH). Men and women aged 60 years and above with ISH defined by a systolic blood pressure (SBP) of 160 mm Hg or higher and diastolic blood pressure lower than 90 mm Hg were randomized to chlorthalidone-based stepped care therapy or matching placebo. Among 4736 SHEP participants, 4073 had a normal orthostatic response, 203 had orthostatic hypertension, and 438 had orthostatic hypotension. Compared with normal response, orthostatic hypertension was associated with higher all-cause mortality at 4.5 and 17 years in analyses adjusted for age, gender, treatment, SBP, and pulse pressure (PP, HR 1.87, 95% CI 1.30-2.69, p = 0.0007; HR 1.40, 95% CI 1.17-1.68, p = 0.0003, respectively). These associations remained significant after additional adjustment for risk factors and comorbidities (HR 1.43, 95% CI 0.99-0.08, p = 0.0566 at 4.5 years, and HR 1.27, 95% CI 1.06-1.53, p = 0.0096 at 17 years). The increased risk of all-cause mortality associated with orthostatic hypertension was observed in both the active and placebo groups without significant interaction between randomization group and the effect on mortality. Orthostatic hypertension is associated with future mortality risk, is easily detected, and can be used in refining cardiovascular risk assessment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Clortalidona/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Posição Ortostática , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Causas de Morte , Clortalidona/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Sístole , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
2.
Eur Heart J ; 40(34): 2899-2906, 2019 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30629157

RESUMO

AIMS: Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke. METHODS AND RESULTS: We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83-0.84) and 0.64-0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment. CONCLUSION: Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predictions of individual-level treatment effects facilitate translation of trial results to individual patients.


Assuntos
Anti-Hipertensivos/uso terapêutico , Aspirina/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Prognóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo
3.
J Diabetes Complications ; 32(9): 830-832, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30030011
4.
Am J Hypertens ; 31(5): 609-614, 2018 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-29360915

RESUMO

BACKGROUND: Impaired renal function is a risk factor for cardiovascular disease, end-stage renal disease (ESRD), and mortality. The impact of short-term renal function decline on outcomes is less well studied. The association of antihypertensive medications with the impact of short-term estimated glomerular filtration rate (eGFR) decline is not known. METHODS: We examined 20,207 hypertensive participants with baseline and 2-year creatinine levels from which eGFR changes were estimated. The associations between eGFR change with incident coronary heart disease (CHD), stroke, heart failure (HF), all-cause mortality, and ESRD during 2.9 years of in-trial follow up, and with mortality during in-trial and post-trial follow-up (7.6 years), were studied. Results were assessed by primary hypertension (HTN) treatment (chlorthalidone, lisinopril, and amlodipine) and adjusted for baseline eGFR levels. RESULTS: In the short run, an eGFR decline below the cohort median (-1.28 ml/minute/1.73 m2/2 years) vs. above the median, or a 5 ml/min/1.73 m2/year decline vs. no decline, was associated with significant hazard risk for CHD (1.06-1.28), HF (1.24-1.91), ESRD (2.84-6.01), and mortality (1.08-1.19), but not with stroke risk. In the long term, there was a significant association with mortality (1.11-1.34). Interaction terms for outcomes by antihypertensive treatments were not statistically significant except for ESRD between amlodipine vs. chlorthalidone (hazard ratio: 3.17 [2.59, 3.88] vs. 2.41 [1.98, 2.97]; P interaction = 0.005) for a 5 ml/min/1.73 m2/year eGFR decline. CONCLUSION: Decline in eGFR over 2 years is associated with increased risk of clinical outcomes beyond the effects of baseline eGFR. These risks were the same irrespective of the primary medication used to treat HTN.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/etiologia , Taxa de Filtração Glomerular , Hipertensão/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Falência Renal Crônica/etiologia , Masculino
5.
Curr Cardiol Rep ; 19(9): 76, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28752275

RESUMO

PURPOSE OF REVIEW: This review summarizes the impact of thiazide diuretics on fracture risk in older hypertensive individuals. RECENT FINDINGS: We performed a post hoc evaluation of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a randomized, prospective, double blind hypertension study comparing a thiazide-like diuretic, a calcium channel blocker (CCB), and an angiotensin converting enzyme inhibitor (ACEi). We examined the risk of hip and pelvic fractures during the in-trial period (n = 22,180 participants; mean 4.9-year follow-up) and during the post-trial period using national data bases (n = 16,622 participants) (mean total follow-up 7.8 years). During the trial, participants randomized to the thiazide diuretic versus the CCB or the ACEi had a lower risk of fracture on adjusted analyses (HR 0.79 [95% CI, 0.63, 0.98], p = 0.04). Risk of fracture was significantly lower in participants randomized to the diuretic as compared to those randomized to the ACEi (HR 0.75 [95% CI, 0.58, 0.98]; p = 0.04), but not significantly different compared to the CCB (HR 0.87 [95% CI, 0.71, 1.09]; p = 0.17). Over the entire trial and post-trial period of follow-up, the cumulative incidence of fractures was non-significantly lower in participants assigned to the diuretic vs assignment to the ACEi or the CCB (HR 0.87 [0.74-1.03], p = 0.10) and versus each medication separately. These findings establish a benefit for thiazide diuretic treatment for the prevention of fractures versus other commonly used antihypertensive medications using prospective, randomized data. The effects of the thiazide diuretic on bone appear to be long lasting.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Densidade Óssea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Diuréticos/farmacologia , Fraturas Ósseas/prevenção & controle , Fraturas do Quadril/prevenção & controle , Hipertensão/tratamento farmacológico , Ossos Pélvicos/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Diuréticos/efeitos adversos , Método Duplo-Cego , Feminino , Fraturas Ósseas/induzido quimicamente , Fraturas do Quadril/induzido quimicamente , Humanos , Masculino , Ossos Pélvicos/lesões , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Hypertension ; 70(1): 94-102, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28559399

RESUMO

Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications.


Assuntos
Anlodipino , Doenças Cardiovasculares/prevenção & controle , Clortalidona , Doxazossina , Hiperlipidemias , Hipertensão , Lisinopril , Idoso , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Análise de Variância , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Clortalidona/administração & dosagem , Clortalidona/efeitos adversos , Doxazossina/administração & dosagem , Doxazossina/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/diagnóstico , Hiperlipidemias/tratamento farmacológico , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lisinopril/administração & dosagem , Lisinopril/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
JAMA Intern Med ; 177(7): 955-965, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28531241

RESUMO

Importance: While statin therapy for primary cardiovascular prevention has been associated with reductions in cardiovascular morbidity, the effect on all-cause mortality has been variable. There is little evidence to guide the use of statins for primary prevention in adults 75 years and older. Objectives: To examine statin treatment among adults aged 65 to 74 years and 75 years and older when used for primary prevention in the Lipid-Lowering Trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). Design, Setting, and Participants: Post hoc secondary data analyses were conducted of participants 65 years and older without evidence of atherosclerotic cardiovascular disease; 2867 ambulatory adults with hypertension and without baseline atherosclerotic cardiovascular disease were included. The ALLHAT-LLT was conducted from February 1994 to March 2002 at 513 clinical sites. Interventions: Pravastatin sodium (40 mg/d) vs usual care (UC). Main Outcomes and Measures: The primary outcome in the ALLHAT-LLT was all-cause mortality. Secondary outcomes included cause-specific mortality and nonfatal myocardial infarction or fatal coronary heart disease combined (coronary heart disease events). Results: There were 1467 participants (mean [SD] age, 71.3 [5.2] years) in the pravastatin group (48.0% [n = 704] female) and 1400 participants (mean [SD] age, 71.2 [5.2] years) in the UC group (50.8% [n = 711] female). The baseline mean (SD) low-density lipoprotein cholesterol levels were 147.7 (19.8) mg/dL in the pravastatin group and 147.6 (19.4) mg/dL in the UC group; by year 6, the mean (SD) low-density lipoprotein cholesterol levels were 109.1 (35.4) mg/dL in the pravastatin group and 128.8 (27.5) mg/dL in the UC group. At year 6, of the participants assigned to pravastatin, 42 of 253 (16.6%) were not taking any statin; 71.0% in the UC group were not taking any statin. The hazard ratios for all-cause mortality in the pravastatin group vs the UC group were 1.18 (95% CI, 0.97-1.42; P = .09) for all adults 65 years and older, 1.08 (95% CI, 0.85-1.37; P = .55) for adults aged 65 to 74 years, and 1.34 (95% CI, 0.98-1.84; P = .07) for adults 75 years and older. Coronary heart disease event rates were not significantly different among the groups. In multivariable regression, the results remained nonsignificant, and there was no significant interaction between treatment group and age. Conclusions and Relevance: No benefit was found when pravastatin was given for primary prevention to older adults with moderate hyperlipidemia and hypertension, and a nonsignificant direction toward increased all-cause mortality with pravastatin was observed among adults 75 years and older. Trial Registration: clinicaltrials.gov Identifier: NCT00000542.


Assuntos
Doenças Cardiovasculares , Pravastatina/administração & dosagem , Idoso , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/análise , Monitoramento de Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Masculino , Conduta do Tratamento Medicamentoso , Avaliação de Processos e Resultados em Cuidados de Saúde , Prevenção Primária/métodos , Prevenção Primária/estatística & dados numéricos , Estados Unidos/epidemiologia
8.
Am J Med ; 130(4): 439-448.e9, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27984005

RESUMO

BACKGROUND: Although hypertension guidelines define treatment-resistant hypertension as blood pressure uncontrolled by ≥3 antihypertensive medications, including a diuretic, it is unknown whether patient prognosis differs when a diuretic is included. METHODS: Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were randomly assigned to first-step therapy with chlorthalidone, amlodipine, or lisinopril. At a Year 2 follow-up visit, those with average blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic on ≥3 antihypertensive medications, or blood pressure <140/90 mm Hg on ≥4 antihypertensive medications were identified as having apparent treatment-resistant hypertension. The prevalence of treatment-resistant hypertension and its association with ALLHAT primary (combined fatal coronary heart disease or nonfatal myocardial infarction) and secondary (all-cause mortality, stroke, heart failure, combined coronary heart disease, and combined cardiovascular disease) outcomes were identified for each treatment group. RESULTS: Of participants assigned to chlorthalidone, amlodipine, or lisinopril, 9.6%, 11.4%, and 19.7%, respectively, had treatment-resistant hypertension. During mean follow-up of 2.9 years, primary outcome incidence was similar for those assigned to chlorthalidone compared with amlodipine or lisinopril (amlodipine- vs chlorthalidone-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.53-1.39; P = .53; lisinopril- vs chlorthalidone-adjusted HR = 1.06; 95% CI, 0.70-1.60; P = .78). Secondary outcome risks were similar for most comparisons except coronary revascularization, which was higher with amlodipine than with chlorthalidone (HR 1.86; 95% CI, 1.11-3.11; P = .02). An as-treated analysis based on diuretic use produced similar results. CONCLUSIONS: In this study, which titrated medications to a goal, participants assigned to chlorthalidone were less likely to develop treatment-resistant hypertension. However, prognoses in those with treatment-resistant hypertension were similar across treatment groups.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Idoso , Anlodipino/administração & dosagem , Anlodipino/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Clortalidona/administração & dosagem , Clortalidona/uso terapêutico , Diuréticos/administração & dosagem , Diuréticos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/complicações , Lisinopril/administração & dosagem , Lisinopril/uso terapêutico , Masculino , Falha de Tratamento , Resultado do Tratamento
9.
JAMA Intern Med ; 177(1): 67-76, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27893045

RESUMO

IMPORTANCE: On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized clinical trials are lacking. OBJECTIVE: To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. DESIGN, SETTING, AND PARTICIPANTS: Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Posttrial follow-up was conducted through the end of 2006, using passive surveillance via national databases. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006. MAIN OUTCOMES AND MEASURES: Hip and pelvic fracture hospitalizations. RESULTS: A total of 22 180 participants (mean [SD] age, 70.4 [6.7] years; 43.0% female; and 49.9% white non-Hispanic, 31.2% African American, and 19.1% other ethnic groups) were followed for up to 8 years (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16 622 participants for whom claims data were available were followed for up to 5 additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial, 338 fractures occurred. Participants randomized to receive chlorthalidone vs amlodipine or lisinopril had a lower risk of fracture on adjusted analyses (hazards ratio [HR], 0.79; 95% CI, 0.63-0.98; P = .04). Risk of fracture was significantly lower in participants randomized to receive chlorthalidone vs lisinopril (HR, 0.75; 95% CI, 0.58-0.98; P = .04) but not significantly different compared with those randomized to receive amlodipine (HR, 0.82; 95% CI, 0.63-1.08; P = .17). During the entire trial and posttrial period of follow-up, the cumulative incidence of fractures was nonsignificantly lower in participants randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87; 95% CI, 0.74-1.03; P = .10) and vs each medication separately. In sensitivity analyses, when 1 year after randomization was used as the baseline (to allow for the effects of medications on bone to take effect), similar results were obtained for in-trial and in-trial plus posttrial follow-up. CONCLUSIONS AND RELEVANCE: These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000542.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Clortalidona/uso terapêutico , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Lisinopril/uso terapêutico , Ossos Pélvicos/lesões , Idoso , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Masculino , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
10.
Clin Nephrol ; 87 (2017)(1): 11-20, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27900942

RESUMO

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) and cancer are both common in older patients; whether CKD increases risk for cancer is unclear. This study evaluated CKD as a risk factor for cancer mortality in a large cohort of hypertensive patients. STUDY DESIGN: We did post-hoc analyses of in-trial and post-trial data from participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). SETTING AND PARTICIPANTS: Participants were ≥ 55 years old with hypertension and one other additional risk factor for coronary heart disease. PREDICTOR: Baseline estimated glomerular filtration rate (eGFR). OUTCOMES: Cancer mortality was ascertained by cancer-related deaths reported in national databases during and after the trial. Cox proportional hazard models were used to calculate hazard ratios (HRs) adjusted for possible confounders and were stratified by baseline GFR. RESULTS: Participants' mean age was 66.9 years. After a mean follow-up of 8.9 years, there were 2,338 reported cancer-related deaths. Participants with GFR < 45 mL/min/1.73 m2 were at increased risk of cancer mortality compared to those with GFR ≥ 90 mL/min/1.73 m2 (adjusted HR 1.54 (1.22 - 1.94), p-value for trend 0.004). These findings were consistent across subgroups defined by race, gender, and diabetes. Participants with GFR < 45 mL/min/1.73 m2 were at higher risk for mortality related to colon cancer (p-value for trend 0.048, HR 2.28 (1.12 - 4.62)) and urinary tract cancer (p-value for trend 0.001, adjusted HR 2.95 (1.14 - 7.65)). LIMITATIONS: This is a post hoc analysis of clinical trial data. CONCLUSIONS: In a large cohort of hypertensive patients, GFR < 45 mL/min/1.73 m2 was associated with a higher risk of cancer-related mortality.


Assuntos
Taxa de Filtração Glomerular , Hipertensão/complicações , Neoplasias/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Idoso , Anti-Hipertensivos/uso terapêutico , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações , Fatores de Risco
11.
Circ Cardiovasc Qual Outcomes ; 9(3): 213-21, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27174798

RESUMO

BACKGROUND: In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. METHODS AND RESULTS: Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was <2% for 13% of the patients. About 30% had an ARR of >4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]). CONCLUSIONS: ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that may complement informed decision making. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00327418 (CARDS) and NCT00000542 (ALLHAT).


Assuntos
Anti-Hipertensivos/uso terapêutico , Atorvastatina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Técnicas de Apoio para a Decisão , Diabetes Mellitus Tipo 2/complicações , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Atorvastatina/efeitos adversos , Biomarcadores/sangue , Tomada de Decisão Clínica , Diabetes Mellitus Tipo 2/diagnóstico , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/diagnóstico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , América do Norte/epidemiologia , Valor Preditivo dos Testes , Fatores de Proteção , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Países Escandinavos e Nórdicos , Fatores de Tempo , Resultado do Tratamento , Reino Unido
12.
Br J Haematol ; 172(1): 122-30, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26523836

RESUMO

Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 µg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r(2)  = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin.


Assuntos
Anemia Falciforme/terapia , Sobrecarga de Ferro/etiologia , Reação Transfusional , Anemia Falciforme/complicações , Anemia Falciforme/metabolismo , Antidrepanocíticos/uso terapêutico , Criança , Feminino , Ferritinas/sangue , Humanos , Hidroxiureia/uso terapêutico , Ferro/metabolismo , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/metabolismo , Rim/metabolismo , Fígado/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pâncreas/metabolismo , Baço/metabolismo , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Ultrassonografia Doppler Transcraniana
13.
Am J Cardiol ; 117(1): 105-15, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26589819

RESUMO

Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Dislipidemias/complicações , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Guias de Prática Clínica como Assunto/normas , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/complicações , Método Duplo-Cego , Dislipidemias/sangue , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Fatores de Risco
14.
J Am Soc Hypertens ; 8(11): 808-19, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25455006

RESUMO

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 = 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 = 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In-trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P = .005, race-by-amlodipine/lisinopril interaction P = .012) and gender (gender-by-lisinopril/amlodipine interaction P = .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period.


Assuntos
Anlodipino/administração & dosagem , Clortalidona/administração & dosagem , Hipertensão/tratamento farmacológico , Lisinopril/administração & dosagem , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Fatores Etários , Idoso , Anlodipino/efeitos adversos , Causas de Morte , Clortalidona/efeitos adversos , Intervalos de Confiança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Estimativa de Kaplan-Meier , Lisinopril/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Taxa de Sobrevida , Resultado do Tratamento
15.
Hypertension ; 64(5): 1012-21, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25259745

RESUMO

Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of ≥3 antihypertensive medication classes or controlled hypertension while treated with ≥4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 [1.18-1.76]), stroke (1.57 [1.18-2.08]), all-cause mortality (1.30 [1.11-1.52]), heart failure (1.88 [1.52-2.34]), peripheral artery disease (1.23 [0.85-1.79]), and end-stage renal disease (1.95 [1.11-3.41]). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Resistência a Medicamentos , Hipertensão/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Infarto do Miocárdio/prevenção & controle , Idoso , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipolipemiantes/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento
16.
Cancer Epidemiol Biomarkers Prev ; 23(8): 1589-97, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24832873

RESUMO

BACKGROUND: Research on the association between antihypertensive drug treatment (HTDT) and cancer is equivocal. We tested the hypothesis that large, rapid decreases in blood pressure following HTDT are associated with higher cancer mortality. METHODS: Data from the Systolic Hypertension in the Elderly Program (SHEP) with 15-year cause-specific follow-up for mortality were used. We used changes from baseline in seated and standing systolic blood pressure (SBP) measurements at 3, 6, 9, and 12 months after the initiation of HTDT. Hazard ratios adjusted for demographics, comorbidities, and competing risk of non-cancer-related deaths were estimated to determine the association between SBP change, as a continuous or time-dependent measure, and cancer-related death. RESULTS: SHEP participants taking antihypertensive medication who exhibited a decrease in seated SBP of 29 mm Hg or more (50th percentile and above) at 3 months were at a 58% greater risk of cancer-related death during a 15-year follow-up compared with those with no decrease in SBP (P = 0.007, 42% increased risk P = 0.02 for standing SBP). Those participants whose maximal seated SBP change occurred in the first 3 months of treatment had 2.6-times greater risk of cancer mortality compared with those whose maximal seated SBP change occurred at 12 months (P = 0.004). CONCLUSIONS: Large SBP decreases early in HTDT were associated with an increased risk of cancer-related death during a 15-year follow-up. Further studies are needed to confirm and explore the potential mechanisms for this association. IMPACT: Rapid decreases in blood pressure following HTDT may be a risk factor for cancer. Cancer Epidemiol Biomarkers Prev; 23(8); 1589-97. ©2014 AACR.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Neoplasias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
17.
J Hypertens ; 32(7): 1503-13; discussion 1513, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24842697

RESUMO

OBJECTIVE: Epidemiologically, there is a strong relationship between BMI and blood pressure (BP) levels. We prospectively examined randomization to first-step chlorthalidone, a thiazide-type diuretic; amlodipine, a calcium-channel blocker; and lisinopril, an angiotensin-converting enzyme inhibitor, on BP control and cardiovascular outcomes in a hypertensive cohort stratified by baseline BMI [kg/m(2); normal weight (BMI <25), overweight (BMI = 25-29.9), and obese (BMI >30)]. METHODS: In a randomized, double-blind, practice-based Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, 33,357 hypertensive participants, aged at least 55 years, were followed for an average of 4.9 years, for a primary outcome of fatal coronary heart disease or nonfatal myocardial infarction, and secondary outcomes of stroke, heart failure, combined cardiovascular disease, mortality, and renal failure. RESULTS: Of participants, 37.9% were overweight and 42.1% were obese at randomization. For each medication, BP control (<140/90 mmHg) was equivalent in each BMI stratum. At the fifth year, 66.1, 66.5, and 65.1% of normal-weight, overweight, and obese participants, respectively, were controlled. Those randomized to chlorthalidone had highest BP control (67.2, 68.3, and 68.4%, respectively) and to lisinopril the lowest (60.4, 63.2, and 59.6%, respectively) in each BMI stratum. A significant interaction (P = 0.004) suggests a lower coronary heart disease risk in the obese for lisinopril versus chlorthalidone (hazard ratio 0.85, 95% confidence interval 0.74-0.98) and a significant interaction (P = 0.011) suggests a higher risk of end-stage renal disease for amlodipine versus chlorthalidone in obese participants (hazard ratio 1.49, 95% confidence interval 1.06-2.08). However, these results were not consistent among other outcomes. CONCLUSION: BMI status does not modify the effects of antihypertensive medications on BP control or cardiovascular disease outcomes.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Obesidade/complicações , Sobrepeso/complicações , Idoso , Idoso de 80 Anos ou mais , Anlodipino/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Clortalidona/uso terapêutico , Estudos de Coortes , Diuréticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Hipertensão/fisiopatologia , Lisinopril/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Obesidade/fisiopatologia , Sobrepeso/patologia , Sobrepeso/fisiopatologia , Estudos Prospectivos
18.
J Clin Hypertens (Greenwich) ; 16(1): 34-40, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24325609

RESUMO

Most studies of an association of visit-to-visit variability of blood pressure with increased risk of future adverse cardiovascular events are of short duration and rarely include a placebo group. Using data from the double-blind, placebo-controlled Systolic Hypertension in the Elderly Program, the authors examined mortality from cardiovascular causes up to 17 years of follow-up using the National Death Index. Visit-to-visit blood pressure variability was associated with cardiovascular death after adjustment for sex, age, serum creatinine, diabetes, body mass index, smoking status, left ventricular failure, and high-density lipoprotein cholesterol. The relationship was significantly stronger in the active treatment group compared with the placebo group. Although this could be the result of an effect of the medications used unrelated to visit-to-visit variability, the data are compatible with the hypothesis that inconsistent adherence leading to missing active medication doses may be an additional explanation for the relationship of visit-to-visit variability with cardiovascular death.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/mortalidade , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Visita a Consultório Médico/estatística & dados numéricos , Fatores Etários , Idoso , Anti-Hipertensivos/farmacologia , Atenolol/farmacologia , Atenolol/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Clortalidona/farmacologia , Clortalidona/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Estudos Longitudinais , Masculino , Cooperação do Paciente , Taxa de Sobrevida , Resultado do Tratamento
19.
Clin Nephrol ; 80(4): 235-48, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23816477

RESUMO

BACKGROUND/AIMS: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). METHODS: Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. RESULTS: Through Year 6, total cholesterol declined in pravastatin (-20.7%) and usualcare groups (-11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory "as-treated" analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 - 0.85), p<0.001) and lover CHD (HR=0.84 (0.73-0.97), p=0.01), but not combined cardiovascular disease (HR=0.95 (0.88-1.04), p=0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. CONCLUSIONS: In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory "as-treated" analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy.


Assuntos
Doença das Coronárias/prevenção & controle , Taxa de Filtração Glomerular/fisiologia , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Pravastatina/uso terapêutico , Insuficiência Renal Crônica/fisiopatologia , Idoso , Doença das Coronárias/complicações , Doença das Coronárias/mortalidade , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
20.
Circ Cardiovasc Qual Outcomes ; 5(2): 153-62, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22396585

RESUMO

BACKGROUND: Thiazide-type diuretics are associated with an increased incidence of diabetes compared with other antihypertensive medications. In this study, we determined the long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared with the effects of incident diabetes associated with calcium channel blocker and angiotensin-converting enzyme inhibitor use. METHODS AND RESULTS: A total of 22 418 participants from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with baseline diabetes, incident diabetes (7.5% with chlorthalidone, 5.6% with amlodipine, and 4.3% with lisinopril), or no diabetes at 2 years of in-trial follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4 additional years posttrial) through the use of national databases. The primary outcome was CVD mortality (death from coronary heart disease [CHD], stroke, heart failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD mortality, and CHD (nonfatal myocardial infarction or fatal CHD). Participants on chlorthalidone with incident diabetes versus no diabetes had consistently lower, nonsignificant risk for CVD mortality (hazard ratio [HR], 1.04; 95% CI, 0.74-1.47), all-cause mortality (HR, 1.04; 95% CI, 0.82-1.30), and non-CVD mortality (HR, 1.05; 95% CI, 0.77-1.42) than participants on amlodipine or lisinopril with incident diabetes (HR range, 1.22-1.53). Participants with incident diabetes had elevated CHD risk compared with those with no diabetes (HR, 1.46; 95% CI, 1.09-1.96), but those on chlorthalidone had significantly lower risk than those on lisinopril (HR, 1.18 versus 2.57; P=0.04 for interaction). CONCLUSIONS: The findings suggest that thiazide-related incident diabetes has less adverse long-term CVD impact than incident diabetes that develops while on other antihypertensive medications.


Assuntos
Doenças Cardiovasculares/mortalidade , Diabetes Mellitus/induzido quimicamente , Hipertensão/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Clortalidona/efeitos adversos , Doença das Coronárias/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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