RESUMO
BACKGROUND: The kidney has the highest level of selenium (Se) in the body, but the role of plasma Se in chronic kidney disease is uncertain. OBJECTIVE: We aimed to investigate the longitudinal association between baseline plasma Se and renal function decline in adults with hypertension and to explore possible effect modifiers. METHODS: This was a post hoc analysis of 935 men and women with hypertension aged 40 to 75 years from a folic-acid intervention trial (the China Stroke Primary Prevention Trial) in China. The baseline plasma Se was analyzed both as a continuous variable and as tertiles. The primary outcome was a rapid decline in renal function, defined as a mean decline in the estimated glomerular filtration rate of ≥ 5 mL/(min × 1.73 m2) per year. RESULTS: The median follow-up duration from baseline to outcome was 4.4 years. After multivariate adjustment, there was an inverse association between plasma Se and a rapid decline in renal function (per 10-unit increment; OR: 0.85; 95% CI: 0.73, 0.99). When the baseline plasma Se was assessed as tertiles, compared to the lowest tertile (<74.5 µg/L), a lower trend of the primary outcome was found in the second tertile (74.5 to < 89.4 µg/L; OR: 0.60; 95% CI: 0.34, 1.07) and the highest tertile (89.4 to <150 µg/L; OR: 0.42; 95% CI: 0.22, 0.80; Ptrend = 0.006). Furthermore, the Se-renal association was more pronounced among participants with folic acid treatment or with a higher baseline folate concentration (both Pinteraction values < 0.05). CONCLUSIONS: In this sample of Chinese adults with hypertension, baseline plasma Se concentrations were inversely associated with the risk of renal function decline. The China Stroke Primary Prevention Trial was registered at clinicaltrials.gov as NCT00794885.
Assuntos
Hipertensão , Selênio , Acidente Vascular Cerebral , Adulto , Feminino , Humanos , Masculino , China , Ácido Fólico , Taxa de Filtração Glomerular , Rim/fisiologia , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controleRESUMO
Acne vulgaris (AV) is a common dermatosis that causes psychological problems. Isotretinoin is the first-line treatment for moderate-to-severe AV, but its onset of effect is delayed. Although light-based therapy is widely used in the treatment of AV, there is a lack of reports on delicate pulsed light (DPL) which has a narrow therapeutic spectrum (500-600 nm). Low-level light therapy (LLLT) has shown an emerging role in anti-inflammatory effects and skin repair. This study investigates the efficacy and safety of low-dose oral isotretinoin combined with LLLT using DPL in patients with moderate-to-severe AV. Thirty-six patients with moderate-to-severe AV were enrolled and received low-dose oral isotretinoin (10-20 mg/day). The two sides of the face were randomly assigned to receive DPL (6-9 J/cm2) or not at an interval of 2 weeks for 4 treatment sessions (weeks 0, 2, 4, 6). Photos, GAGS score, counts of papules, pustules, comedones, TEWL, melanin and erythema index, side effects, efficacy, and satisfactory score were recorded at each visit and at 4 weeks after the final treatment (week 10). Thirty-three patients completed the study. DPL and oral isotretinoin combined therapy exhibited significantly improved GAGS score as well as the number of the lesions from week 2 and maintained until week 10. At the end of the observation, the improvement of GAGS was 70.88% on the DPL and isotretinoin combined side versus 62.12% on the side with isotretinoin monotherapy (p = 0.0009). The improvement for papule number was 61.58% on the DPL combined side versus 43.33% on the control side (p < 0.0001), for comedone was 63.15% versus 43.30% (p = 0.0008). TEWL and indexes of melanin and erythema also had better outcomes with DPL combined therapy at week 10. All the side effects were temporary and tolerable; no adverse effects were observed. Oral low-dose isotretinoin combined with LLLT by DPL offers a combination with reduced side effects and better outcomes within a limited treatment duration, which advances the onset of effect of isotretinoin monotherapy and improves lesion clearance.
Assuntos
Acne Vulgar , Terapia com Luz de Baixa Intensidade , Acne Vulgar/tratamento farmacológico , Administração Oral , Anti-Inflamatórios/uso terapêutico , Eritema/induzido quimicamente , Eritema/tratamento farmacológico , Humanos , Isotretinoína/efeitos adversos , Melaninas , Resultado do TratamentoRESUMO
BACKGROUND: Previous studies have indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relation between circulating selenium and risk of first stroke remains inconclusive. OBJECTIVES: We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. METHODS: In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. RESULTS: During a median follow-up duration of 4.5 y (IQR: 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline [≥7.7 ng/mL (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, compared with <7.7 ng/mL, adjusted OR: 0.98; 95% CI: 0.80, 1.21; P-interaction = 0.008] and those with higher time-averaged systolic blood pressure (SBP) over the treatment period (≥140 mm Hg, adjusted OR: 0.71; 95% CI: 0.58, 0.86, compared with <140 mm Hg, adjusted OR: 0.96; 95% CI: 0.77, 1.20; P-interaction = 0.023). CONCLUSIONS: There was a significant inverse association between plasma Se and risk of first stroke in Chinese adults with hypertension, especially among those with higher baseline folate concentrations and those with higher time-averaged SBP over the treatment period. This trial was registered at clinicaltrials.gov as NCT00794885.
Assuntos
Hipertensão/sangue , Selênio/sangue , Acidente Vascular Cerebral/etiologia , Anti-Hipertensivos/uso terapêutico , Povo Asiático/estatística & dados numéricos , Fatores de Risco Cardiometabólico , Estudos de Casos e Controles , China , Método Duplo-Cego , Enalapril/uso terapêutico , Feminino , Ácido Fólico/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevenção Primária , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/prevenção & controle , Complexo Vitamínico B/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: Fat-based energy-dense nutritional supplements may offer benefits over protein- or carbohydrate-dense supplements for patients receiving dialysis because of the adverse metabolic consequences of the latter. We conducted a randomized controlled trial to assess the effects of the short-term use of a fat-based nutritional supplement on various measures of nutritional status in patients receiving maintenance hemodialysis who have low dietary energy intake. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled nondiabetic patients receiving hemodialysis for >3 months who had inadequate dietary energy intake (<30 kcal/kg per day). The participants were randomly assigned in a 1:1 ratio to receive an oral fat-based energy-dense supplement (300 kcal daily) or routine care for 12 weeks (n=120 per group). The primary outcome was the change in phase angle measured by bioelectrical impedance analysis, a marker of cell integrity and body cell mass, from the baseline to week 12. The secondary outcomes were changes in quality of life. Other outcomes included laboratory nutritional indicators and physical examinations. RESULTS: The average age of the total population was 47 (SD: 12) years, and 55% were men. The median of dialysis vintage was 43.4 (22.5-76.3) months; 240 participants were randomly assigned to the intervention (n=120) or control group (n=120). In total, 228 (95%) participants completed the trial. The change in phase angle did not differ significantly between the intervention and control groups (estimate, 0.0; 95% confidence interval, -0.1 to 0.1 versus estimate, 0.0; 95% confidence interval, -0.1 to 0.1; estimated difference, 0.0; 95% confidence interval -0.2 to 0.2; P=0.99). None of the 19 domains of quality of life differed between the groups. Adverse events were reported in 23 (19%) participants in the control group and 40 (33%) participants in the intervention group. CONCLUSIONS: In nondiabetic patients on maintenance hemodialysis, short-term administration of fat-based energy-dense nutritional supplement has no clinically significant effect on nutritional status as measured by phase angle. PODCAST: This article contains a podcast at https://https://www.asn-online.org/media/podcast/CJASN/2021_08_03_CJN16821020.mp3.
Assuntos
Gorduras na Dieta/administração & dosagem , Suplementos Nutricionais , Estado Nutricional/efeitos dos fármacos , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Administração Oral , Adulto , Gorduras na Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Impedância Elétrica , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Diálise RenalRESUMO
Generally, ginsenosides have the physiological effect of an anti-inflammatory immunity. After fermentation, the types of ginsenosides in ginseng change, and their physiological activity becomes a concern. L. plantarum KP-4 screened from Korean kimchi were used to ferment ginseng, and the changes of ginsenosides were observed. C57BL/6N mice were treated using fermented ginseng (390 mg kg-1 day-1), which was mixed with normal food, and an inflammatory mice model was established by the intraperitoneal injection of lipopolysaccharide (LPS) (2.5 mg per kg body weight) four weeks later. The liver index, pathological index, biochemical index, and inflammatory signaling pathway were determined. The results demonstrated that L. plantarum KP-4 fermentation increased the content of minor ginsenosides in ginseng and decreased the content of major ginsenosides. Fermented ginseng significantly reduced LPS-induced increases in ALT, AST, and pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß in mice. Supplementation with fermented ginseng significantly ameliorated LPS-induced overexpression of Toll-like receptor 4 (TLR4), caspase3, phosphorylation p38 mitogen-activated protein kinase (p38MAPK), and phosphorylation extracellular signal-regulated kinase (ERK) compared with the control group. Moreover, fermented ginseng significantly increased the expression of claudin 1, the intestinal tight junction protein, caused by LPS. In conclusion, fermented ginseng alleviates LPS-induced inflammation through the TLR4/MAPK signaling pathway and increased intestinal barrier function in mice.
Assuntos
Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Panax/química , Receptor 4 Toll-Like/metabolismo , Animais , Fermentação , Trato Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/química , Ginsenosídeos/metabolismo , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genéticaRESUMO
RATIONALE & OBJECTIVE: In populations with folic acid fortification or supplementation, the main nutritional determinant of total homocysteine levels is vitamin B12 (B12) status. We aimed to evaluate the modifying effect of B12 levels on the association between folic acid treatment and chronic kidney disease (CKD) progression. STUDY DESIGN: A post hoc analysis of an interventional trial. SETTING & PARTICIPANTS: This is a post hoc analysis of 1,374 hypertensive adults with mild to moderate CKD and B12 measurements at baseline from the kidney disease substudy of the China Stroke Primary Prevention Trial (CSPPT), conducted in 20 communities in Jiangsu province in China, a region with low folate consumption. INTERVENTIONS: Assignments to a double-blinded daily treatment of enalapril, 10mg, and folic acid, 0.8mg; or enalapril, 10mg, alone. OUTCOMES: The primary outcome was progression of CKD (defined as a decrease in estimated glomerular filtration rate [eGFR] ≥ 30% and to a level of<60mL/min/1.73m2 if baseline eGFR was≥60mL/min/1.73m2; or a decrease in eGFR≥50% if baseline eGFR was<60mL/min/1.73m2; or kidney failure). RESULTS: Mean baseline eGFR in this study was 86.1±20.5 (SD) mL/min/1.73m2. Median treatment duration was 4.4 years. Among participants with higher baseline B12 levels (≥248pmol/L), compared to enalapril alone, enalapril-folic acid treatment was associated with an 83% reduction in the odds of the primary outcome (OR, 0.17; 95% CI, 0.07-0.40). However, among those with baseline B12 levels<248pmol/L (metabolic B12 deficiency), there was no significant group difference in the primary outcome (OR, 1.21; 95% CI, 0.51-2.85). The interaction between B12 level and folic acid treatment was significant (P = 0.001). LIMITATIONS: The analysis is post hoc and event rate is low. CONCLUSIONS: Folic acid treatment was associated with a greater reduction in the odds of CKD progression among patients with mild to moderate CKD and higher B12 levels. FUNDING: Government funding (National Key Research and Development Program of China).
Assuntos
Ácido Fólico/administração & dosagem , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/tratamento farmacológico , Vitamina B 12/administração & dosagem , Idoso , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagemRESUMO
OBJECTIVE: The association between plasma selenium and new-onset diabetes in hypertensive adults is still unclear. We aimed to evaluate the relationship of baseline plasma selenium with new-onset diabetes and examine possible effect modifiers in a post-hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). METHODS: A total of 2367 hypertensive, non-diabetic patients with plasma selenium measurements at baseline were included. The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during the follow-up period, or fasting glucose (FG) ≥126.0â¯mg/dL at the exit visit. RESULTS: At baseline, higher FG levels were found among participants with plasma selenium in quartile 4 (≥94.8⯵g/L) (ß, 1.64â¯mg/dL; 95%CI: 0.54, 2.73) compared to those in quartiles 1-3. During a median follow-up duration of 4.5 years, new-onset diabetes occurred in 270 (11.4%) participants. Graphic plot showed a positive association between baseline selenium levels and risk of new-onset diabetes. This was further confirmed by adjusted regression analyses; the odds ratios (OR) for new-onset diabetes comparing quartile 4 (≥94.8⯵g/L) to quartiles 1-3 was 1.36 (95%CI: 1.01, 1.83). No clear trend was evident across quartiles 1-3. CONCLUSIONS: Our data suggest that high plasma selenium (≥94.8⯵g/L) was associated with increased risk of new-onset diabetes in hypertensive patients.
Assuntos
Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Hipertensão/complicações , Selênio/sangue , Adulto , Glicemia/análise , Jejum/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 µmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 µmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60-<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.
Assuntos
Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Hipertensão/sangue , Idoso , China , Método Duplo-Cego , Feminino , Seguimentos , Genótipo , Taxa de Filtração Glomerular , Humanos , Hiper-Homocisteinemia/terapia , Hipertensão/terapia , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Fumar , Acidente Vascular Cerebral/prevenção & controleRESUMO
OBJECTIVE: We aimed to evaluate whether proteinuria and estimated glomerular filtration rate (eGFR) levels can modify the efficacy of folic acid therapy on the risk of all-cause mortality among hypertensive patients in the China Stroke Primary Prevention Trial, a randomized, double-blind, and controlled trial. METHODS: A total of 20â702 hypertensive patients without a history of major cardiovascular diseases were randomly assigned to a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (nâ=â10â348), or 10-mg enalapril alone (nâ=â10â354). All-cause mortality, a prespecified endpoint of the China Stroke Primary Prevention Trial, was the main outcome in this analysis. RESULTS: Over a median treatment duration of 4.5 years, in the enalapril alone group, both heavy proteinuria [vs. absent, 10.8 vs. 2.7%; hazard ratioâ=â3.30; 95% confidence interval (CI): 2.10-5.18] and lower eGFR levels (<60 vs. ≥90âml/min per 1.73âm, 13.0 vs. 2.2%; hazard ratioâ=â1.93; 95% CI: 1.19-3.12) were significantly associated with increased risk of all-cause mortality. Folic acid supplementation significantly reduced the risk of all-cause mortality in patients with heavy proteinuria (6.4% in the enalapril-folic acid vs. 10.8% in the enalapril alone group, hazard ratioâ=â0.49; 95% CI: 0.26-0.94), but not in those with absent or mild proteinuria (2.8 vs. 2.9%, hazard ratioâ=â0.99; 95% CI: 0.84-1.17; P for interactionâ=â0.040). However, eGFR levels did not significantly modify the effect of folic acid supplementation in reducing the risk of all-cause mortality (P for interactionâ=â0.228). CONCLUSION: Among hypertensive patients without a history of major cardiovascular diseases, folic acid therapy could reduce the mortality risk associated with heavy proteinuria.
Assuntos
Ácido Fólico/uso terapêutico , Hipertensão/tratamento farmacológico , Proteinúria/mortalidade , Complexo Vitamínico B/uso terapêutico , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Enalapril/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Hipertensão/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteinúria/prevenção & controle , RiscoRESUMO
OBJECTIVE: To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials. METHODS: Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model. FINDINGS: Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84-0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67-0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90-1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77-0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90-1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69-0.88) or low baseline vitamin B12 levels (<384 pg/mL: 0.78, 0.68-0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (p for interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of vitamin B12, a low prevalence of statin use, but a high prevalence of hypertension. CONCLUSIONS: Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low vitamin B12 levels.
Assuntos
Ácido Fólico/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: The effect of folic acid supplementation on uric acid (UA) concentrations is still inconclusive.Objective: We aimed to test the efficacy of folic acid therapy in reducing serum UA in hypertensive patients.Design: A total of 15,364 hypertensive patients were randomly assigned to a double-blind daily treatment with a single tablet that contained 10 mg enalapril and 0.8 mg folic acid (n = 7685) or 10 mg enalapril alone (n = 7679). The main outcome was the change in serum UA, which was defined as UA at the exit visit minus that at baseline. Secondary outcomes were as follows: 1) controlled hyperuricemia (UA concentration <357 µmol/L after treatment) and 2) new-onset hyperuricemia in participants with normal UA concentrations (<357 µmol/L).Results: After a median of 4.4 y of treatment, the mean ± SD UA concentration increased by 34.7 ± 72.5 µmol/L in the enalapril-alone group and by 30.7 ± 71.8 µmol/L in the enalapril-folic acid group, which resulted in a mean group difference of -4.0 µmol/L (95% CI: -6.5, -1.6 µmol/L; P = 0.001). Furthermore, compared with enalapril alone, enalapril-folic acid treatment showed an increase in controlled hyperuricemia (30.3% compared with 25.6%; OR: 1.31; 95% CI: 1.01, 1.70) and a decrease in new-onset hyperuricemia (15.0% compared with 16.3%; OR: 0.89; 95% CI: 0.79, 0.99). A greater beneficial effect was observed in subjects with hyperuricemia (P-interaction = 0.07) or higher concentrations of total homocysteine (tHcy) (P-interaction = 0.02) at baseline. Furthermore, there was a significant inverse relation (P < 0.001) between the reduction of tHcy and the change in UA concentrations.Conclusions: Enalapril-folic acid therapy, compared with enalapril alone, can significantly reduce the magnitude of the increase of UA concentrations in hypertensive adults. This trial was registered at clinicaltrials.gov as NCT00794885.
Assuntos
Ácido Fólico/uso terapêutico , Hipertensão/sangue , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangue , Complexo Vitamínico B/uso terapêutico , Idoso , China , Suplementos Nutricionais , Método Duplo-Cego , Combinação de Medicamentos , Enalapril/farmacologia , Enalapril/uso terapêutico , Feminino , Ácido Fólico/farmacologia , Homocisteína/sangue , Humanos , Hiperuricemia/sangue , Hiperuricemia/complicações , Masculino , Pessoa de Meia-Idade , Razão de Chances , Acidente Vascular Cerebral , Complexo Vitamínico B/farmacologiaRESUMO
The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT and TT), were randomly assigned to receive double-blind daily treatment with a single pill containing 10 mg enalapril and 0.8 mg folic acid(n = 10,348) or a pill containing 10 mg enalapril alone(n = 10,354). During a median treatment duration of 4.5 years, cancer occurred in 116 participants(1.12%) in the enalapril-folic acid group versus 116 participants(1.12%) in the enalapril group (HR, 1.00; 95%CI, 0.77-1.29). There was also no significant difference in the HRs for specific types of cancer(esophageal, gastric, breast, lung, colorectal, head and neck, liver and gynecologic cancer or lymphoma) or cancer mortality(HR, 1.05; 95%CI, 0.69-1.58). For participants not receiving folic acid treatment (enalapril only group), MTHFR 677 TT genotype was an independent predictor of total cancer risk compared to CC genotype (HR, 1.86; 95%CI, 1.07-3.22). Consistently, a beneficial effect was observed in participants with MTHFR TT genotype and low folate levels (<9.0 ng/mL; HR, 0.47; 95%CI, 0.24-0.94). There is no evidence that 0.8 mg daily folic acid supplementation can increase the risk of cancer incidence among adults with hypertension without history of stroke or MI in China. Our data suggest a protective effect in participants with MTHFR TT genotype and low folate levels.
Assuntos
Anti-Hipertensivos/administração & dosagem , Enalapril/administração & dosagem , Ácido Fólico/administração & dosagem , Hipertensão/tratamento farmacológico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Neoplasias/epidemiologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , China/epidemiologia , Suplementos Nutricionais , Método Duplo-Cego , Esquema de Medicação , Enalapril/uso terapêutico , Feminino , Ácido Fólico/uso terapêutico , Humanos , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. METHODS: A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. RESULTS: The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). CONCLUSIONS: Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.