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The association between dietary Cu intake and mortality risk remains uncertain. We aimed to investigate the relationship of dietary Cu intake with all-cause mortality among Chinese adults. A total of 17 310 participants from the China Health and Nutrition Survey, a national ongoing open cohort of Chinese participants, were included in the analysis. Dietary intake was measured by three consecutive 24-h dietary recalls in combination with a weighing inventory over the same 3 d. The average intakes of the 3-d dietary macronutrients and micronutrients were calculated. The study outcome was all-cause mortality. During a median follow-up of 9·0 years, 1324 (7·6 %) participants died. After adjusting for sex, age, BMI, ever alcohol drinking, ever smoking, education levels, occupations, urban or rural residents, systolic blood pressure, diastolic blood pressure and the intakes of fat, protein and carbohydrate, the association between dietary Cu intake and all-cause mortality followed a J-shape (Pfor nonlinearity = 0·047). When dietary Cu intake was assessed as quartiles, compared with those in the first quartile (<1·60 mg/d), the adjusted hazard ratios for all-cause mortality were 0·87 (95 % CI (0·71, 1·07)), 0·98 (95 % CI (0·79, 1·21)) and 1·49 (95 % CI (1·19, 1·86)), respectively, in participants in the second (1·60–<1·83 mg/d), third (1·83–<2·09 mg/d) and fourth (≥2·09 mg/d) quartiles. A series of subgroup analyses and sensitivity analyses showed similar results. Overall, our findings emphasised the importance of maintaining optimal dietary Cu intake levels for prevention of premature death.
We aim to examine the relation of several folate forms (5-methyltetrahydrofolate (5-mTHF), unmetabolised folic acid (UMFA) and MeFox) with kidney function and albuminuria, which remained uncertain. The cross-sectional study was conducted in 18 757 participants from National Health and Nutrition Examination Survey 2011–2018. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) (<60 ml/min/1·73 m2), microalbuminuria (albumin:creatinine ratio (ACR) of 30–299 mg/g) and macroalbuminuria (ACR ≥ 300 mg/g). Overall, there were significant inverse associations between serum 5-mTHF and kidney outcomes with significant lower prevalence of reduced eGFR (OR, 0·71; 95 % CI: 0·57, 0·87) and macroalbuminuria (OR, 0·65; 95 % CI: 0·46, 0·91) in participants in quartiles 3–4 (v. quartiles 1–2; both Pfor trend across quartiles <0·05). In contrast, there were significant positive relationship between serum UMFA and kidney outcomes with significant higher prevalence of reduced eGFR in participants in quartiles 2–4 (v. quartile 1; OR, 2·12; 95 % CI: 1·45, 3·12; Pfor trend <0·001) and higher prevalence of macroalbuminuria in participants in quartile 4 (v. quartiles 1–3; OR, 1·46; 95 % CI: 1·06, 2·01; Pfor trend <0·001). However, there was no significant associations of 5-mTHF and UMFA with microalbuminuria. In addition, there were significant positive relationships of serum MeFox with reduced eGFR, microalbuminuria and macroalbuminuria (all Pfor trend <0·01). In conclusion, higher 5-mTHF level, along with lower UMFA and MeFox level, was associated with lower prevalence of kidney outcomes, which may help counsel future clinical trials and nutritional guidelines regarding the folate supplement.
High fibre intake is associated with reduced mortality risk in both general and chronic kidney disease populations. However, in dialysis patients, such data are limited. Therefore, the association between dietary fibre intake (DFI) and the risk of all-cause and CVD mortality was examined in this study. A total of 1044 maintenance haemodialysis (MHD) patients from eight outpatient dialysis centres in China were included in this study. Data on DFI were collected using 24-h dietary recalls for 3 d in a week and were normalised to actual dry weight. The study outcomes included all-cause and CVD mortality. Over a median of 46 months of follow-up, 354 deaths were recorded, of which 210 (59 %) were due to CVD. On assessing DFI as tertiles, the CVD mortality risk was significantly lower in patients in tertiles 2–3 (≥0·13 g/kg per d; hazard ratio (HR) 0·71; 95 % CI 0·51, 0·97) compared with those in tertile 1 (<0·13 g/kg per d). A similar but non-significant trend was found for the association between DFI (tertiles 2–3 v. tertile 1; HR 0·83; 95 % CI 0·64, 1·07) and all-cause mortality. In summary, higher DFI was associated with lower CVD mortality risk among Chinese MHD patients. This study emphasises the significance of DFI in MHD patients and provides information that is critical for the improvement of dietary guidelines for dialysis patients.
We aimed to examine whether baseline neutrophil counts affected the risk of new-onset proteinuria in hypertensive patients, and, if so, whether folic acid treatment is particularly effective in proteinuria prevention in such a setting. A total of 8208 eligible participants without proteinuria at baseline were analysed from the renal substudy of the China Stroke Primary Prevention Trial. Participants were randomised to receive a double-blind daily treatment of 10 mg of enalapril and 0·8 mg of folic acid (n 4101) or 10 mg of enalapril only (n 4107). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The mean age of the participants was 59·5 (sd, 7·4) years, 3088 (37·6 %) of the participants were male. The median treatment duration was 4·4 years. In the enalapril-only group, a significantly higher risk of new-onset proteinuria was found among participants with higher neutrophil counts (quintile 5; ≥4·8 × 109/l, OR 1·44; 95 % CI 1·00, 2·06), compared with those in quintiles 1–4. For those with enalapril and folic acid treatment, compared with the enalapril-only group, the new-onset proteinuria risk was reduced from 5·2 to 2·8 % (OR 0·49; 95 % CI 0·29, 0·82) among participants with higher neutrophil counts (≥4·8 × 109/l), whereas there was no significant effect among those with neutrophil counts <4·8 × 109/l. In summary, among hypertensive patients, those with higher neutrophil counts had increased risk of new-onset proteinuria, and this risk was reduced by 51 % with folic acid treatment.
We aimed to evaluate the relationship of plasma Mg with the risk of new-onset hyperuricaemia and examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the present study. The main outcome was new-onset hyperuricaemia defined as a UA concentration ≥417 μmol/l in men or ≥357 μmol/l in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4·3 years, new-onset hyperuricaemia occurred in 290 (17·2 %) participants. There was a significantly inverse relation of plasma Mg with the risk of new-onset hyperuricaemia (per sd increment; OR 0·85; 95 % CI 0·74, 0·99) and change in UA levels (per sd increment; β −3·96 μmol/l; 95 % CI −7·14, −0·79). Consistently, when plasma Mg was analysed as tertiles, a significantly lower risk of new-onset hyperuricaemia (OR 0·67; 95 % CI 0·48, 0·95) and less increase in UA levels (β −8·35 μmol/l; 95 % CI −16·12, −0·58) were found among participants in tertile 3 (≥885·5 μmol/l) compared with those in tertile 1 (<818·9 μmol/l). Similar trends were found in males and females. Higher plasma Mg levels were associated with a decreased risk of new-onset hyperuricaemia in hypertensive adults.
Maintenance haemodialysis (MHD) is the use of a machine to filter wastes, salts and fluid from blood for at least 3 months to prolong the life of patients with advanced kidney failure. Although low dietary energy intake (DEI) has been observed in MHD patients, few studies have related DEI to the risk of mortality. To explore this relationship, a study included 1039 MHD patients from eight centres was conducted. DEI was assessed by three 24-h diet recalls and was normalised to ideal body weight (IBW). All-cause mortality and CVD mortality were the primary and secondary outcomes, respectively. During a median follow-up of 28 months, a U-shaped relationship was observed between DEI and all-cause or CVD mortality. The risk of all-cause mortality decreased significantly with the increase of DEI in participants with DEI <167·4 kJ/kg IBW per d (hazard ratio (HR) 0·98; 95 % CI 0·96, 1·00) and increased significantly with the increase of DEI in those with DEI ≥167·4 kJ/kg IBW per d (HR 1·12; 95 % CI 1·04, 1·20). Similarly, the risk of CVD mortality decreased with the increase of DEI in participants with DEI <152·7 kJ/kg IBW per d (HR 0·96; 95 % CI 0·93, 0·99) and increased with the increase of DEI in participants with DEI ≥152·7 kJ/kg IBW per d (HR 1·11; 95 % CI 1·04, 1·18). In summary, there was a U-shaped association between DEI and all-cause or CVD mortality, with a turning point at about 167·4 and 152·7 kJ/kg IBW per d, respectively, in MHD patients.
We aimed to investigate the association between plasma retinol and incident cancer among Chinese hypertensive adults. We conducted a nested case–control study, including 231 patients with incident cancer and 231 matched controls during a median 4·5-year follow-up of the China Stroke Primary Prevention Trial. There was a significant, inverse association between retinol levels and digestive system cancer (per 10 μg/dl increases: OR 0·79; 95 % CI 0·69, 0·91). When compared with participants in the first quartile of retinol (< 52·3 μg/dl), a significantly lower cancer risk was found in participants in quartile 2–4 ( ≥ 52·3 μg/dl: OR 0·31; 95 % CI 0·13, 0·71). However, there was a U-shaped association between retinol levels and non-digestive system cancers where the risk of cancers decreased (although not significantly) with each increment of plasma retinol (per 10 μg/dl increases: OR 0·89; 95 % CI 0·60, 1·31) in participants with retinol < 68·2 μg/dl, and then increased significantly with retinol (per 10 μg/dl increase: OR 1·65; 95 % CI 1·12, 2·44) in participants with retinol ≥ 68·2 μg/dl. In conclusion, there was a significant inverse dose–response association between plasma retinol and the risk of digestive system cancers. However, a U-shaped association was observed between plasma retinol and the risk of non-digestive cancers (with a turning point approximately 68·2 μg/dl).
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.
We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma homocysteine (tHcy) ≥ 10 μmol/l) and its major determinants in rural Chinese hypertensive patients. A cross-sectional investigation was carried out in Lianyungang of Jiangsu province, China. This analysis included 13 946 hypertensive adults. The prevalence of hyperhomocysteinaemia was 51·6 % (42·7 % in women and 65·6 % in men). The OR of hyperhomocysteinaemia were 1·52 (95 % CI 1·39, 1·67) and 2·32 (95 % CI 2·07, 2·61) for participants aged 55–65 and 65–75 v. 45–55 years; 1·27 (95 % CI 1·18, 1·37) for participants with a BMI ≥ 25 v. < 25 kg/m2; 1·14 (95 % CI 1·06, 1·23) for participants with v. without antihypertensive treatment; 1·09 (95 % CI 1·00, 1·18) for residents inland v. coastal; 0·89 (95 % CI 0·82, 0·97) and 0·83 (95 % CI 0·74, 0·92) for participants with moderate and high v. low physical activity levels; 1·54 (95 % CI 1·41, 1·68) and 2·47 (95 % CI 2·17, 2·81) for participants with a glomerular filtration rate 60–90 and < 60 v. ≥ 90 ml/min per 1·73 m2; and 1·20 (95 % CI 1·07, 1·35) and 3·81 (95 % CI 3·33, 4·36) for participants with CT and TT v. CC genotype at methylenetetrahydrofolate reductase 677C>T polymorphism, respectively. Furthermore, higher tHcy concentrations were observed in smokers of both sexes (men: geometric mean 12·1 (interquartile range (IQR) 9·2–14·5) v. 11·9 (IQR 9·3–14·0) μmol/l, P= 0·005; women: geometric mean 10·3 (IQR 8·3–13·0) v. 9·6 (IQR 7·8–11·6) μmol/l, P= 0·010), and only in males with hypertension grade 3 (v. grade 1 or controlled blood pressure) (geometric mean 12·1 (IQR 9·2–14·4) v. 11·7 (IQR 9·2–14·0), P= 0·016) and in male non-drinkers (yes v. no) (geometric mean 12·3 (IQR 9·4–14·8) v. 11·7 (IQR 9·1–13·9), P= 0·014). In conclusion, there was a high prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as folic acid supplementation and lifestyle change.
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