Publications by authors named "Binyan Wang"

154 Publications

Egg consumption associated with all-cause mortality in rural China: a 14-year follow-up study.

Eur J Public Health 2021 May 5. Epub 2021 May 5.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Background: Dietary recommendations regarding egg intake remain controversial topic for public health. We hypothesized that there was a positive association between egg consumption and all-cause mortality.

Methods: To test this hypothesis, we enrolled 9885 adults from a community-based cohort in Anhui Province, China during 2003-05. Egg consumption was assessed by food questionnaire. Stratified analyses were performed for age, sex, body mass index (BMI), blood pressure, smoking, drinking and laboratory tests.

Results: After an average follow-up of 14.1 years, 9444 participants were included for analysis. A total of 814 deaths were recorded. Participants' BMI and lipid profile had no significantly difference between three egg consumption groups. BMI was 21.6±2.7 of the whole population, especially BMI>24 was only 17.3%. A bivariate association of egg consumption >6/week with increased all-cause mortality was observed compared with ≤6/week (RR: 1.35, 95% CI: 1.05, 1.73, P = 0.018). A significant interaction was observed for BMI ≥ 21.2 kg/m2 vs. BMI<21.2 kg/m2 (P for interaction: 0.001). No other significant interactions were found.

Conclusions: In this study, consuming >6 eggs/week increased risk of all-cause mortality, even among lean participants, especially who with BMI ≥ 21.2 kg/m2. Eggs are an easily accessible and constitute an affordable food source in underdeveloped regions. Consuming <6 eggs/week may be the most suitable intake mode.
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http://dx.doi.org/10.1093/eurpub/ckaa250DOI Listing
May 2021

Association of visceral adiposity index with new-onset type 2 diabetes and impaired fasting glucose in hypertensive Chinese adults.

Eat Weight Disord 2021 Apr 12. Epub 2021 Apr 12.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou, 510515, China.

Purpose: Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults.

Methods: A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose < 6.1 mmol/L at baseline, while fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L at the exit visit.

Results: Over a median of 4.5 years' follow-up, 1612 (10.9%) participants developed type 2 diabetes. When VAI was categorized into quartiles, compared with participants in quartile 1-3 (< 2.80), significantly higher risk of new-onset type 2 diabetes (OR 1.30; 95% CI 1.08-1.56) and new-onset IFG (OR 1.28; 95% CI 1.08-1.52) was found in those in quartile 4 (≥ 2.80). Moreover, the positive associations were consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) levels; or with different numbers of abnormal VAI components (all P interactions > 0.05).

Conclusion: Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components.

Level Of Evidence: Level III, a well-designed cohort.
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http://dx.doi.org/10.1007/s40519-021-01187-4DOI Listing
April 2021

Prospective association between baseline plasma zinc concentration and development of proteinuria in Chinese hypertensive patients.

J Trace Elem Med Biol 2021 Apr 2;66:126755. Epub 2021 Apr 2.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510515, China. Electronic address:

Objective: We aimed to evaluate the association between baseline plasma zinc and the development of proteinuria as well as possible effect modifiers in hypertensive patients.

Methods: This is a subset of the China Stroke Primary Prevention Trial (CSPPT) Renal Sub-Study. In the CSPPT, participants were randomized to receive a daily oral dose of 1 tablet containing 10 mg enalapril and 0.8 mg folic acid or 1 tablet containing 10 mg enalapril only. A total of 783 participants with plasma zinc measurements and without proteinuria at baseline were included in the current study. The study outcome was the development of proteinuria during the follow-up, defined as a urine dipstick reading of trace or ≥1+ at the exit visit.

Results: During a median follow-up duration of 4.4 years, the development of proteinuria occurred in 93 (11.9 %) participants. There was an inverse relation of baseline plasma zinc with the development of proteinuria (per SD increment; OR, 0.74, 95 % CI: 0.55-0.99), p for trend of quartiles = 0.005.

Conclusions: In Chinese hypertensive patients, there was a significant inverse association between baseline plasma zinc and the development of proteinuria, although plasma zinc remained in the reference range.
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http://dx.doi.org/10.1016/j.jtemb.2021.126755DOI Listing
April 2021

Cigarette smoking and all-cause mortality in rural Chinese male adults: 15-year follow-up of the Anqing cohort study.

BMC Public Health 2021 Apr 9;21(1):696. Epub 2021 Apr 9.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Background: According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population.

Methods: Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates.

Results: There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23-2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33-2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43-2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83-5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034).

Conclusions: This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.
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http://dx.doi.org/10.1186/s12889-021-10691-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034075PMC
April 2021

Comparing the measurement properties of the EQ-5D-5L and the EQ-5D-3L in hypertensive patients living in rural China.

Qual Life Res 2021 Apr 5. Epub 2021 Apr 5.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Purpose: The purpose of this study was to compare the measurement properties of two versions of EQ-5D (i.e.EQ-5D-3L and EQ-5D-5L) in hypertensive patients in rural China.

Methods: A cross-sectional survey was carried out in hypertensive patients in rural China. We compared the ceiling effects, redistribution properties, informativity, known-groups validity, and relative efficiency of the 3L and 5L and examined their agreement.

Results: A total of 11,412 patients were enrolled in our study. The mean EQ-5D index score was 0.84 (SD 0.21) according to the 5L and 0.86 (SD 0.17) according to the 3L. A good agreement was observed between the 3L and 5L. The overall ceiling effect decreased from 46.4% (3L) to 29.4% (5L). The Shannon index, H' improved in all dimensions when used 5L. When used 3L, the median responses of all groups were consistent with 5L across the three dimensions of 'mobility', 'self-care', 'usual activities', while the median responses were inconsistent for the 'pain/discomfort' and 'anxiety/depression' dimensions. The 3L performed better in eight comorbidities in terms of F-statistics and six comorbidities in terms of the area under the receiver operating characteristic curves (AUROCs). The 5L performed better both in terms of the F-statistics and AUROCs in age, education level, anti-hypertensive medication use.

Conclusion: Taking all comparisons into account, we recommend the EQ-5D-5L for use in patients with hypertension in rural China.
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http://dx.doi.org/10.1007/s11136-021-02786-5DOI Listing
April 2021

Neutrophil counts and the risk of first stroke in general hypertensive adults.

Hypertens Res 2021 Feb 9. Epub 2021 Feb 9.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

We aimed to investigate the association between neutrophil counts and first stroke and examine possible effect modifiers among treated hypertensive adults. This is a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). A total of 11,878 hypertensive adults with data on neutrophil counts at baseline were included in the current study. The primary outcome was first stroke. During a median follow-up of 4.5 years, 414 (3.5%) participants experienced a first stroke, including 358 with ischemic stroke, 55 with hemorrhagic stroke and one with uncertain type of stroke. Compared with participants in quartile 1 (<2.9 × 10/L) of neutrophil counts, those in the upper quartiles (quartile 2-4 [≥2.9 × 10/L]) had a significantly higher risk of first stroke (HR, 1.35; 95% CI: 1.02, 1.78) or first ischemic stroke (HR, 1.38; 95% CI: 1.02, 1.86). Moreover, a strong positive association between neutrophil counts and first ischemic stroke was found in participants with total homocysteine (tHcy) levels <15 μmol/L (HR, 1.74; 95% CI: 1.17, 2.58; vs. ≥15 μmol/L; HR, 0.91; 95% CI: 0.57, 1.46, P interaction = 0.042) at baseline or time-averaged mean arterial pressure (MAP) ≥102 mmHg (median) (HR, 1.92; 95% CI: 1.27, 2.89; vs. <102 mmHg; HR, 0.89; 95% CI: 0.57, 1.41, P interaction = 0.015) during the treatment period. However, no such association between neutrophil counts and first hemorrhagic stroke was found. In summary, high baseline neutrophil counts were associated with an increased risk of first ischemic stroke among hypertensive patients, especially in those with low tHcy at baseline or high time-averaged MAP during the treatment period.
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http://dx.doi.org/10.1038/s41440-021-00625-1DOI Listing
February 2021

Association between plasma copper levels and first stroke: a community-based nested case-control study.

Nutr Neurosci 2021 Feb 3:1-10. Epub 2021 Feb 3.

Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi, People's Republic of China.

Background And Aims: Uncertainty remains regarding the association between the risk of stroke and plasma copper levels in population with copper mostly in normal range due to limited data. We examined the association between baseline plasma copper and risk of first stroke in Chinese community-dwelling population.

Methods: We conducted a nested case control study from 'H-type Hypertension and Stroke Prevention and Control Project'. A total of 1255 first stroke cases and 1255 controls matched for age, sex and study site were included in the analysis. Conditional logistic regression analyses were performed to evaluate the association between plasma copper and first stroke.

Results: The overall mean of copper was 15.90 (2.66) μmol/L. In total, 94.26% participants' copper concentration was in the normal range by Mayo Clinic laboratory reference values. Smoothing curve showed that the associations of plasma copper with first stroke and its subtypes were linear. Each standard deviation (SD) increment of plasma copper was independently and positively associated with risk of first stroke [odds ratio (OR): 1.17, 95% confidence interval (CI): 1.07-1.28]. The multivariable ORs with 95% CIs for total stroke, ischemic stroke and hemorrhagic stroke in the highest versus the lowest quartile of plasma copper were 1.49 (1.16-1.90; -trend = 0.001), 1.46 (1.12-1.92; -trend = 0.004) and 2.05 (0.95-4.38; -trend = 0.050), respectively.

Conclusions: Baseline plasma copper was positively associated with risk of first ischemic stroke in an approximately linear fashion among Chinese community population (80.32% hypertensives), although their copper levels were mostly within the normal range according to current reference values. Our findings warrant additional investigation.
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http://dx.doi.org/10.1080/1028415X.2021.1875299DOI Listing
February 2021

Relation of BMI and waist circumference with the risk of new-onset hyperuricemia in hypertensive patients.

QJM 2021 Jan 24. Epub 2021 Jan 24.

Institute of Biomedicine, Anhui Medical University, Hefei, China.

Background: We aimed to evaluate the relationship of body mass index (BMI) and waist circumference (WC) with the risk of new-onset hyperuricemia, and examine possible effect modifies in general hypertensive patients.

Methods: A total of 10,611 hypertensive patients with normal uric acid (UA) concentrations (<357μmol/L) at baseline were included from the UA Sub-study of the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset hyperuricemia, defined as a UA concentration ≥417μmol/L in men or ≥ 357μmol/L in women at the exit visit.

Results: During a median follow-up duration of 4.4 years, 1663 (15.7%) participants developed new-onset hyperuricemia. When analyzed separately, increased BMI (≥25 kg/m2, quartile 3-4; OR, 1.46; 95% CI: 1.29-1.65), or increased WC (≥85cm for females, quartile 3-4; OR, 1.24; 95% CI: 1.08-1.42; and ≥84cm for males, quartile 3-4; OR, 1.30; 95% CI: 1.01-1.67) were each significantly associated with higher risk of new-onset hyperuricemia. When WC was forced into the model with BMI simultaneously, its significant association with new-onset hyperuricemia disappeared in females (<85 versus ≥85cm; OR, 0.96, 95% CI: 0.81-1.13) or males (≥84 versus <84cm; OR, 1.13; 95%CI: 0.84-1.52); however, BMI was still significantly related with new-onset hyperuricemia (≥25 versus <25kg/m2; OR, 1.48; 95%CI: 1.27-1.73). Moreover, the positive BMI & new-onset hyperuricemia association was more pronounced in participants with higher time-averaged on-treatment SBP (median: <138.3 versus ≥138.3 mmHg; P-interaction = 0.041).

Conclusions: Higher BMI, but not WC, is significantly and independently associated with an increased risk of new-onset hyperuricemia among hypertensive patients.
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http://dx.doi.org/10.1093/qjmed/hcaa346DOI Listing
January 2021

Total bone mineral density is inversely associated with stroke: a family osteoporosis cohort study in rural China.

QJM 2021 Jan 16. Epub 2021 Jan 16.

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

Background: The relationship of osteoporosis and stroke is still not fully clarified. Apart from the well-known risk factors for stroke, bone mineral density (BMD) has gained more interest in recent years.

Aim: To further elucidate the relationship between BMD and stroke risk, a prospective cohort study in the Chinese rural population was conducted.

Design: Retrospective analysis of a family osteoporosis cohort.

Methods: Our subjects were selected from an osteoporosis cohort conducted in Anqing, China. All participants underwent a questionnaire assessment, clinical examinations, and laboratory assessments. During the follow-up period, the number of people who had a stroke was recorded. Generalized estimating equation regression analysis was performed to determine the significance of the association between BMD and stroke.

Results: A total of 17868 people were included. A two-way interaction test of sex and BMD on stroke was significant (p = 0.002). There was a significant difference in BMD and stroke morbidity in the male group (p = 0.003). When BMD was assessed as quartiles and the lowest quartile was used as reference, a significantly lower risk for stroke were observed in Q2, Q3 and Q4. Notably, no significant difference was observed in female participants with adjusted odds ratio (p > 0.05). The p-value for interaction was calculated. The BMI (p = 0.014) and waist-to-hip ratio (p = 0.027) were found to be significantly associated with BMD and stroke risk in female participants.

Conclusions: In Chinese rural areas, total BMD may negatively correlated with stroke, especially in men.
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http://dx.doi.org/10.1093/qjmed/hcaa339DOI Listing
January 2021

Degree of blood pressure control and the risk of new-onset hyperuricemia in treated hypertensive patients.

Ann Transl Med 2020 Nov;8(21):1434

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangzhou, China.

Background: The relationship between blood pressure (BP) control and the risk of new-onset hyperuricemia remains uncertain. We aimed to examine the association between degree of time-averaged on-treatment BP control and new-onset hyperuricemia in general hypertensive patients.

Methods: A total of 10,617 hypertensive patients with normal uric acid (UA) concentrations (<357 µmol/L) at baseline were included from the UA Sub-study of the China Stroke Primary Prevention Trial (CSPPT). Participants were randomized to receive a double-blind daily treatment of enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. BP measurements were taken every three months after randomization. The primary outcome was new-onset hyperuricemia, defined as a UA concentration ≥417 µmol/L in men or ≥357 µmol/L in women at the exit visit.

Results: Over a median of 4.4 years, 1,664 (15.7%) participants developed new-onset hyperuricemia. Overall, there was a significantly positive association between time-averaged on-treatment diastolic BP (DBP) and new-onset hyperuricemia (per 10 mmHg increment; OR 1.13; 95% CI: 1.02-1.26). Consistently, a significantly higher risk of new-onset hyperuricemia was found in participants with time-averaged on-treatment DBP ≥82.9 mmHg (median) (. <82.9 mmHg; 17.3% . 14.1%; OR 1.25; 95% CI: 1.10-1.44). Furthermore, the lowest new-onset hyperuricemia risk (12.1%) was found in those with both time-averaged on-treatment SBP (median: 138.3 mmHg) and DBP below the median (P-interaction=0.023). The results were similar for time-averaged DBP during the first 12- or 24-month treatment period, or in the analysis using propensity scores. Furthermore, a non-significant higher risk of new-onset hyperuricemia was observed in participants with time-averaged on-treatment SBP ≥120 mmHg (. <120 mmHg; OR 1.61; 95% CI: 0.88-2.97).

Conclusions: A tight DBP control of <82.9 mmHg was associated with lower risk of new-onset hyperuricemia among hypertensive patients without hyperuricemia.
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http://dx.doi.org/10.21037/atm-20-3017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723605PMC
November 2020

Plasma 25-Hydroxyvitamin D3 Concentrations and Risk of New-Onset Proteinuria in Patients With Hypertension.

J Ren Nutr 2020 Dec 9. Epub 2020 Dec 9.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China. Electronic address:

Objective: We aimed to evaluate the relationship of plasma 25-hydroxyvitamin D3 (25[OH]D3) with the risk of new-onset proteinuria and examine the possible effect modifiers in patients with hypertension and without chronic kidney disease at baseline.

Methods: This is a post hoc analysis of the renal substudy of the China Stroke Primary Prevention Trial. A total of 1655 patients with hypertension, who had plasma 25(OH)D3 measurements, as well as without proteinuria and with an estimated glomerular filtration rate of ≥60 mL/min/1.73 m at baseline, were included in the present study. The main outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit.

Results: The mean (standard deviation) 25(OH)D3 level at baseline was 18.6 (7.5) ng/mL. The median follow-up duration was 4.4 years. Overall, there was a significant inverse association between plasma 25(OH)D3 and the risk of new-onset proteinuria (per standard deviation increment; [odds ratio] OR: 0.70; 95% confidence interval [CI]: 0.50, 0.97). Accordingly, when 25(OH)D3 was assessed as quartiles, a significantly lower risk of new-onset proteinuria was found in participants in quartiles 3-4 (≥17.8 ng/mL; OR: 0.45; 95% CI: 0.23, 0.87), compared with those in quartile 1 (<13.1 ng/mL). Furthermore, a stronger inverse relationship of plasma 25(OH)D3 and new-onset proteinuria was observed in nondiabetic participants (per standard deviation increment; OR: 0.57; 95% CI: 0.39, 0.83; vs. diabetics: OR: 1.48; 95% CI: 0.67, 3.28; P for interaction = 0.028).

Conclusion: There was a significant inverse association between plasma 25(OH)D3 and the risk of proteinuria in patients with hypertension, especially in those without diabetes.
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http://dx.doi.org/10.1053/j.jrn.2020.09.005DOI Listing
December 2020

Interaction of neutrophil counts and folic acid treatment on new-onset proteinuria in hypertensive patients.

Br J Nutr 2020 Dec 14:1-8. Epub 2020 Dec 14.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou510515, People's Republic of China.

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.
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http://dx.doi.org/10.1017/S000711452000505XDOI Listing
December 2020

Plasma Magnesium Concentrations and Risk of Incident Cancer in Adults with Hypertension: A Nested Case-Control Study.

Ann Nutr Metab 2020 3;76(5):304-312. Epub 2020 Dec 3.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Objective: The association between plasma magnesium and risk of incident cancer remains inconclusive in previous studies. We aimed to investigate the prospective relationship of baseline plasma magnesium concentrations with the risk of incident cancer and to examine possible effect modifiers.

Methods: A nested case-control study with 228 incident cancer cases and 228 matched controls was conducted using data from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013. Study outcomes included incident cancer and its subtypes.

Results: When plasma magnesium concentrations were assessed as quartiles, a significantly higher incident risk of total cancer was found in participants in quartile 1 (<0.76 mmol/L; odds ratio [OR] = 2.70; 95% CI: 1.33-5.49) and quartile 4 (≥0.89 mmol/L; OR = 2.05; 95% CI: 1.12-3.76), compared with those in quartile 3 (0.83 to <0.89 mmol/L). In cancer site-specific analyses, similar trends were found for gastrointestinal cancer, esophageal cancer, gastric cancer, breast cancer, lung cancer, and other cancers. Furthermore, none of the variables, including age, sex, current smoking status, current alcohol intake, BMI, systolic blood pressure, and total cholesterol levels at baseline significantly modified the association between plasma magnesium and cancer risk.

Conclusions: Both low and high plasma magnesium concentrations were significantly associated with an increased incident risk of cancer, compared with the reference concentrations of 0.83 to <0.89 mmol/L among hypertensive adults.
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http://dx.doi.org/10.1159/000510214DOI Listing
December 2020

Relationship of Weight Change Patterns From Young to Middle Adulthood With Incident Cardiovascular Diseases.

J Clin Endocrinol Metab 2021 Jan;106(2):e812-e823

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.

Context: The effect of weight change patterns on cardiovascular diseases (CVD) remains uncertain.

Objective: We aim to examine the relation of weight change patterns and absolute weight change from young adulthood to midlife with incident CVD.

Design: Retrospective cohort study.

Setting: National Health and Nutrition Examination Survey 1999-2016.

Participants: A total of 20 715 US adults aged 40 through 79 with recalled weight at young adulthood (25 years) and midlife (10 years before baseline).

Main Outcome Measure: CVD status was determined by self-report of a prior diagnosis, and age at diagnosis was used to establish time of CVD onset. CVD events was defined as the first occurrence of a congestive heart failure, coronary heart disease, angina pectoris, heart attack, or stroke.

Results: After 9.76 years of follow-up, compared with participants who remained at normal weight, those in maximum overweight, changing from nonobese to obese, changing from obese to nonobese, maintaining obesity between young and middle adulthood had a 39% (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.19-1.62), 93% (HR, 1.93; 95% CI, 1.64-2.28), 125% (HR, 2.25; 95% CI, 1.29-3.94), and 132% (HR, 2.32; 95% CI, 1.68-3.20) higher risk of CVD, respectively. In addition, compared with weight change within 2.5 kg, weight gain ≥ 10.0 kg was associated with higher risk of CVD.

Conclusions: Both nonobese to obese, obese to nonobese, and stable obese from young to middle adulthood were associated with increased risks of CVD. The findings emphasize the importance of maintaining normal weight throughout the adulthood for preventing CVD in later life.
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http://dx.doi.org/10.1210/clinem/dgaa823DOI Listing
January 2021

Interaction of serum calcium and folic acid treatment on first stroke in hypertensive males.

Clin Nutr 2021 Apr 23;40(4):2381-2388. Epub 2020 Oct 23.

Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; National Clinical Research Center for Kidney Disease, Guangzhou 510515, China; State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China. Electronic address:

Background & Aims: The role of serum calcium on the risk of stroke is still uncertain. We aimed to evaluate the effect of serum calcium on first stroke risk, and on the efficacy of folic acid treatment in prevention of first stroke among hypertensive patients.

Methods: Our analyses included a total of 19,644 eligible hypertensive adults from the China Stroke Primary Prevention Trial (CSPPT). In the CSPPT, a total of 20,702 hypertensive patients 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. The primary outcome was a first stroke.

Results: Over a median of 4.5 years, among those not receiving folic acid, a significantly higher risk of first stroke was found in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L (median) (vs. <2.43 mmol/L; 6.5% vs. 2.3%; adjusted HR, 2.47; 95% CI: 1.72, 3.55). For those with enalapril and folic acid treatment, compared with the enalapril only group, the risk of first stroke was reduced from 6.5% to 3.0% (adjusted HR, 0.49; 95% CI: 0.35, 0.68) in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L, whereas there was no significant effect among hypertensive males with baseline albumin-corrected serum calcium <2.43 mmol/L. However, among hypertensive females, serum calcium did not significantly affect the first stroke risk and the efficacy of folic acid in prevention of first stroke.

Conclusions: Among Chinese hypertensive males, those with elevated serum calcium levels had increased risk of first stroke, and this risk was reduced by 51% with folic acid treatment.
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April 2021

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults.

Cardiovasc Diabetol 2020 10 24;19(1):186. Epub 2020 Oct 24.

Division of Nephrology, Nanfang Hospital, Southern Medical UniversityNational Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510515, China.

Background: The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.

Methods: A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG < 6.1 mmol/L at baseline and ≥ 6.1 but < 7.0 mmol/L at the exit visit.

Results: Over a median of 4.5 years follow-up, 1549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95% CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95% CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) < 10 μmol/L (adjusted OR, 1.24; 95% CI: 1.10, 1.40 vs. ≥ 10 μmol/L: adjusted OR, 1.03; 95% CI: 0.96, 1.10; P-interaction = 0.007) or FG ≥ 5.9 mmol/L (adjusted OR, 1.16; 95% CI: 1.07, 1.27 vs. < 5.9 mmol/L: adjusted OR, 1.00; 95% CI: 0.93, 1.08; P-interaction = 0.009) CONCLUSIONS: In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels. Clinical Trial Registration-URL Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.
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http://dx.doi.org/10.1186/s12933-020-01161-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585682PMC
October 2020

Vitamin B and risk of diabetes: new insight from cross-sectional and longitudinal analyses of the China Stroke Primary Prevention Trial (CSPPT).

BMJ Open Diabetes Res Care 2020 10;8(1)

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China

Introduction: Previous studies in mostly Western populations have yielded conflicting findings on the association of vitamin B with diabetes risk, in part due to differences in study design and population characteristics. This study sought to examine the vitamin B-diabetes association in Chinese adults with hypertension by both cross-sectional and longitudinal analyses.

Research Design And Methods: This report included a total of 16 699 participants from the China Stroke Primary Prevention Trial, with pertinent baseline and follow-up data. Diabetes mellitus was defined as either physician-diagnosed diabetes, use of glucose-lowering drugs, or fasting blood glucose (FBG) ≥7.0 mmol/L. New-onset diabetes was defined as any new case of onset diabetes during the follow-up period or FBG ≥7.0 mmol/L at the exit visit.

Results: At baseline, there were 1872 (11.2%) patients with diabetes; less than 1.5% had clinical vitamin B deficiency (<148.0 pmol/L). Over a median follow-up period of 4.5 years, there were 1589 (10.7%) cases of new-onset diabetes. Cross-sectional analyses showed a positive association between baseline vitamin B levels and FBG levels (β=0.18, 95% CI 0.15 to 0.21) and diabetes (OR=1.16, 95% CI 1.10 to 1.21). However, longitudinal analyses showed no association between baseline vitamin B and new-onset diabetes or changes in FBG levels. Among a subset of the sample (n=4366) with both baseline and exit vitamin B measurements, we found a positive association between an increase in vitamin B and an increase in FBG.

Conclusions: In this large Chinese population of patients with hypertension mostly sufficient with vitamin B, parallel cross-sectional and longitudinal analyses provided new insight into the conflicting findings of previous studies, and these results underscore the need for future studies to consider both baseline vitamin B and its longitudinal trajectory in order to better elucidate the role of vitamin B in the development of diabetes. Such findings would have important clinical and public health implications.
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http://dx.doi.org/10.1136/bmjdrc-2020-001423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539576PMC
October 2020

Association Between Fasting Blood Glucose and All-Cause Mortality in a Rural Chinese Population: 15-Year Follow-Up Cohort Study.

Diabetes Ther 2020 Nov 25;11(11):2691-2701. Epub 2020 Sep 25.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Introduction: The worldwide prevalence of diabetes has been increasing for decades; diabetes can lead to serious health problems and even death, but the effects of maintaining low fasting blood glucose (FBG) remain controversial. The purpose of this study was to investigate the relationship between FBG levels and all-cause mortality in a long-term follow-up cohort and to find a relatively safe range of FBG levels.

Methods: This study included 17,902 adults from a community-based cohort study in rural China who were prospectively followed from 2003 to 2018. Generalized estimating equations were used to evaluate the association between FBG and all-cause mortality, adjusting for pertinent covariates and auto-correlations among siblings.

Results: A total of 1053 (5.9%) deaths occurred during 15 years of follow-up. There was a significant U-shaped association between all-cause mortality and FBG. Compared with the reference group (FBG of 5.6 - < 6.1 mmol/l), the risk of death among individuals with FBG levels < 5.6 mmol/l significantly increased by 38% (OR 1.34; 95% CI 1.13-1.59), while the risk of death among individuals with FBG ≥ 6.1 mmol/l or participants with a self-reported history of diabetes significantly increased by 51% (OR 1.49; 95% CI 1.20-1.85). Additionally, the U-shaped association remained steady in any stratification of risk factors.

Conclusion: Our study showed a significant U-shaped relationship between FBG levels and risk of all-cause mortality in this rural Chinese population. When FBG was within the range of 5.6 - < 6.1 mmol/l, the risk of all-cause mortality was the lowest.
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http://dx.doi.org/10.1007/s13300-020-00927-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547918PMC
November 2020

Serum folate modified the association between low-density lipoprotein cholesterol and carotid intima-media thickness in Chinese hypertensive adults.

Nutr Metab Cardiovasc Dis 2020 11 24;30(12):2303-2311. Epub 2020 Jul 24.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang of Jiangxi, China. Electronic address:

Background And Aims: While folate is known for its importance in cardiovascular health, it is unknown whether folate status can modify the association between low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (CIMT). We aimed to investigate this question in a Chinese hypertensive population, who are at high-risk of low folate and atherosclerosis.

Methods And Results: This report included 14,970 hypertensive adults (mean age 64.5 years; 40.3% male) from the China Stroke Primary Prevention Trial (CSPPT) and analyzed the fasting serum LDL-C and folate, and CIMT data obtained at the last follow-up visit. LDL-C was calculated using the Friedewald equation. Serum folate levels were measured by chemiluminescent immunoassay. CIMT was measured by ultrasound. Non-parametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the LDL-C-CIMI relationship and effect modification by folate. Consistent with graphic plots, multivariate linear regression showed that LDL-C levels were independently and positively associated with CIMT (β = 7.69, 95%CI: 5.76-9.62). More importantly, the relationship between LDL-C and CIMT was significantly attenuated with increasing serum folate levels (1st tertile: β = 10.06, 95%CI: 6.67-13.46; 2nd tertile: β = 6.81, 95%CI: 3.55-10.07; 3rd tertile: β = 5.96, 95%CI: 2.55-9.36; P-interaction = 0.045). Subgroup analyses showed the association between LDL-C and CIMT across serum folate tertiles was robust among various strata (all P-interaction >0.05).

Conclusions: Among Chinese hypertensive adults, the serum folate levels could modify the association between LDL-C and CIMT. Our findings, if further confirmed, have important clinical implications.
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http://dx.doi.org/10.1016/j.numecd.2020.07.021DOI Listing
November 2020

Positive relationship of hypertensive retinopathy with carotid intima--media thickness in hypertensive patients.

J Hypertens 2020 10;38(10):2028-2035

Department of Ophthalmology, Peking University First Hospital, Beijing.

Objectives: We aimed to explore the relationship of hypertensive retinopathy with carotid intima--media thickness (CIMT), and to examine the possible effect modifiers in Chinese adults with hypertension.

Methods: We conducted a cross-sectional study of 12 342 hypertensive patients with complete exit site visit data from the China Stroke Primary Prevention Trial. CIMT was measured by carotid ultrasonography. Hypertensive retinopathy was diagnosed according to the Keith--Wagener--Barker classification.

Results: The mean (SD) CIMT among study participants was 739.9 (111.4) μm. Compared with patients with grade 1 hypertensive retinopathy or without hypertensive retinopathy, a significantly higher CIMT level (β, 7.63, 95% CI: 2.54--12.73) was observed in patients with grade 2-4 hypertensive retinopathy. Moreover, the association between hypertensive retinopathy (grade 2-4 versus grade 1 or normal) and CIMT was stronger in participants of younger age (<60 years; β, 13.70, 95% CI: 5.65--21.75; versus ≥60 years; β, 1.03, 95% CI: -5.58 to 7.63; P interaction = 0.006); or with lower total homocysteine levels [<12.1 μmol/l (median); β, 12.70, 95% CI: 5.98--19.42; versus ≥12.1 μmol/l; β, 2.07, 95% CI: -5.63 to 9.78; P interaction = 0.030). None of the other variables, including sex, BMI, study centers, treatment group, SBP, triglycerides, total cholesterol, fasting blood glucose, folate, serum creatinine, current smoking and alcohol drinking, significantly modified the relation of hypertensive retinopathy with CIMT levels.

Conclusion: Hypertensive retinopathy (grade 2 and higher) was significantly associated with increased CIMT in hypertensive patients. The association was stronger in those of younger age or with lower total homocysteine levels.
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http://dx.doi.org/10.1097/HJH.0000000000002509DOI Listing
October 2020

Degree of Blood Pressure Control and Incident Diabetes Mellitus in Chinese Adults With Hypertension.

J Am Heart Assoc 2020 08 5;9(16):e017015. Epub 2020 Aug 5.

National Clinical Research Center for Kidney Disease State Key Laboratory for Organ Failure Research Division of Nephrology Nanfang HospitalSouthern Medical University Guangzhou China.

Background The association between blood pressure (BP) control and incident diabetes mellitus remains unknown. We aim to investigate the association between degree of time-averaged on-treatment systolic blood pressure (SBP) control and incident diabetes mellitus in hypertensive adults. Methods and Results A total of 14 978 adults with hypertension without diabetes mellitus at baseline were included from the CSPPT (China Stroke Primary Prevention Trial). Participants were randomized double-masked to daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. BP measurements were taken every 3 months after randomization. The primary outcome was incident diabetes mellitus, defined as physician-diagnosed diabetes mellitus, or use of glucose-lowering drugs during follow-up, or fasting glucose ≥126 mg/dL at the exit visit. Over a median of 4.5 years, a significantly higher risk of incident diabetes mellitus was found in participants with time-averaged on-treatment SBP 130 to <140 mm Hg (10.3% versus 7.4%; odds ratio [OR], 1.37; 95% CI, 1.15‒1.64), compared with those with SBP 120 to <130 mm Hg. Moreover, the risk of incident diabetes mellitus increased by 24% (OR, 1.24; 95% CI, 1.00‒1.53) and the incidence of regression to normal fasting glucose (<100 mg/dL) decreased by 29% (OR, 0.71; 95% CI, 0.57‒0.89) in participants with intermediate BP control (SBP/diastolic blood pressure, 130 to <140 and/or 80 to <90 mm Hg), compared with those with a tight BP control of <130/<80 mm Hg. Similar results were found when the time-averaged BP were calculated using the BP measurements during the first 6- or 24-month treatment period, or in the analysis using propensity scores. Conclusions In this non-diabetic, hypertensive population, SBP control in the range of 120 to <130 mm Hg, compared with the 130 to <140 mm Hg, was associated with a lower risk of incident diabetes mellitus.
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http://dx.doi.org/10.1161/JAHA.120.017015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660809PMC
August 2020

Association of self-reported sleep duration and quality with BaPWV levels in hypertensive patients.

Hypertens Res 2020 12 16;43(12):1392-1402. Epub 2020 Jul 16.

Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

The association between sleep conditions and arterial stiffness remains inconclusive. We aimed to investigate the relationship of sleep duration and quality with brachial-ankle pulse-wave velocity (baPWV) in hypertensive patients. A total of 14,485 hypertensive adults were included in this cross-sectional analysis. Information about sleep duration and quality was obtained via questionnaire. A baPWV level ≥1800 cm/s was defined as indicative of arterial stiffness. Compared with participants with a sleep duration <8 h per day, participants with a sleep duration ≥8 h per day had a significantly higher baPWV level (β = 13.7 cm/s; 95% CI: 3.9, 23.5) and a nonsignificantly higher prevalence of arterial stiffness (39.7% vs. 33.0%; OR, 1.08; 95% CI: 0.99-1.19). Similarly, compared with participants with good or medium sleep quality, participants with poor sleep quality had a significantly higher baPWV level (β = 16.3 cm/s; 95% CI: 0.1, 32.6) and a nonsignificantly greater prevalence of arterial stiffness (36.6% vs. 35.3%; OR, 1.13; 95% CI: 0.97-1.32). When sleep duration and quality were examined jointly, participants with a sleep duration ≥8 h and/or poor sleep quality had a significantly higher baPWV level (β = 14.4 cm/s; 95% CI: 5.3, 23.4) and a greater prevalence of arterial stiffness (38.8% vs. 32.7%; OR, 1.10; 95% CI: 1.01-1.20) than those with a sleep duration <8 h and good/medium sleep quality. In summary, among hypertensive patients, a longer sleep duration (≥8 h per day) and poor sleep quality were associated with higher baPWV levels and a higher prevalence of arterial stiffness.
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http://dx.doi.org/10.1038/s41440-020-0509-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671938PMC
December 2020

Relationship of visceral adiposity index with new-onset proteinuria in hypertensive patients.

Clin Nutr 2021 Feb 2;40(2):438-444. Epub 2020 Jun 2.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Background & Aims: Visceral adiposity index (VAI) is a sex-specific surrogate marker of adipose tissue distribution and function. Little is known about the longitudinal relationship between VAI and proteinuria. This study aimed to examine the prospective relationship of baseline VAI with new-onset of proteinuria in hypertensive patients without major cardiovascular diseases.

Methods: A total of 10 699 hypertensive patients without proteinuria (negative urine dipstick reading) at baseline from the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT) were included. Participants were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. Participants were followed every 3 months after randomization. The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The secondary outcome was progression of proteinuria, defined as a urine dipstick reading of trace or ≥1+ at the exit visit.

Results: During a median follow-up duration of 4.4 years, a total of 396 (3.7%) participants developed new-onset proteinuria, while 1236 (11.6%) participants met progression of proteinuria. When VAI was categorized into quartiles, compared with participants in quartile 1-3 (<2.99), a significantly higher risk of new-onset proteinuria (OR, 1.43; 95%CI: 1.07-1.91) and progression of proteinuria (OR, 1.23; 95%CI: 1.03-1.46) was found in those in quartile 4 (≥2.99). Moreover, the positive association was consistent in participants with or without general obesity, abdominal obesity, and dyslipidemia (all P-interactions > 0.05).

Conclusions: There was a positive association between VAI levels and the risk of new-onset proteinuria in hypertensive patients.
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http://dx.doi.org/10.1016/j.clnu.2020.05.031DOI Listing
February 2021

Achieving blood pressure control targets in hypertensive patients of rural China - a pilot randomized trial.

Trials 2020 Jun 11;21(1):515. Epub 2020 Jun 11.

Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Background: This study aimed to test the feasibility and titration methods used to achieve specific blood pressure (BP) control targets in hypertensive patients of rural China.

Methods: A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke or cardiovascular disease. The patients were randomly assigned to one of three systolic-BP target groups: standard: 140 to < 150 mmHg; moderately intensive: 130 to < 140 mmHg; and intensive: < 130 mmHg. The patients were followed for 6 months.

Discussion: The optimal target for systolic blood pressure (SBP) lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7%, and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP-control protocols that fully consider the population's characteristics, such as age, sex, socio-economic status, compliance with medication, education level, and lifestyle. This randomized trial showed the feasibility and safety of the titration protocol to achieve desirable SBP targets (< 150, < 140, and < 130 mmHg) in a sample of rural, Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2 mmHg, 131.1 mmHg, and 124.2 mmHg, respectively, in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 h after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intensive group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events, including dry cough, palpitations, and arthralgia, were low and showed no significant differences between the three groups. This trial provided real-world experience and laid the foundation for a future, large-scale, BP target study.

Trial Registration: Feasibility Study of the Intensive Systolic Blood Pressure Control; ClinicalTrials.gov, ID: NCT02817503. Registered retrospectively on 29 June 2016.
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http://dx.doi.org/10.1186/s13063-020-04368-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291427PMC
June 2020

Baseline Serum Bilirubin and Risk of First Stroke in Hypertensive Patients.

J Am Heart Assoc 2020 06 3;9(12):e015799. Epub 2020 Jun 3.

National Clinical Research Center for Kidney Disease the State Key Laboratory for Organ Failure Research Renal Division Nanfang Hospital Southern Medical University Guangzhou China.

Background Data on the association between serum bilirubin and the risk of stroke are limited and inconclusive. We aimed to evaluate the association between serum bilirubin and the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods and Results Our study was a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). A total of 19 906 hypertensive patients were included in the final analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of first stroke associated with serum bilirubin levels. The median follow-up period was 4.5 years. When serum total bilirubin was assessed as tertiles, the adjusted HR of first ischemic stroke for participants in tertile 3 (12.9-34.1 μmol/L) was 0.75 (95% CI, 0.59-0.96), compared with participants in tertile 1 (<9.3 μmol/L). When direct bilirubin was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (2.5-24.8 μmol/L) (adjusted HR, 0.77; 95% CI, 0.60-0.98), compared with those in tertile 1 (<1.6 μmol/L). However, there was no significant association between serum total bilirubin (tertile 3 versus 1: adjusted HR, 1.45; 95% CI, 0.89-2.35) or direct bilirubin (tertile 3 versus 1: adjusted HR, 1.27; 95% CI, 0.76-2.11) and first hemorrhagic stroke. Conclusions In this sample of Chinese hypertensive patients, there was a significant inverse association between serum total bilirubin or direct bilirubin and the risk of first ischemic stroke.
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http://dx.doi.org/10.1161/JAHA.119.015799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429063PMC
June 2020

Positive association of serum uric acid with new-onset diabetes in Chinese women with hypertension in a retrospective analysis of the China Stroke Primary Prevention Trial.

Diabetes Obes Metab 2020 09 21;22(9):1598-1606. Epub 2020 May 21.

Division of Nephrology, National Clinical Research Centre for Kidney Disease, State Key Laboratory for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Aims: To investigate the association of baseline serum uric acid (UA) with new-onset diabetes, and to explore the possible effect modifiers in Chinese adults with hypertension.

Materials And Methods: A total of 14 943 hypertensive patients with available UA measurements and without diabetes at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). Participants were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥7.0 mmol/L at the exit visit.

Results: Over a median follow-up of 4.5 years, 1623 participants (10.9%) developed diabetes. Overall, there was a positive association between baseline UA and new-onset diabetes in women (per SD increment; adjusted odds ratio [OR] 1.14, 95% confidence interval [CI] 1.07, 1.23), but not in men (adjusted OR 1.01, 95% CI 0.92, 1.10). Moreover, a stronger positive association between baseline UA and new-onset diabetes was found among women with lower time-averaged on-treatment systolic blood pressure during the treatment period (<140 vs. ≥140 mmHg; P-interaction = 0.024), higher baseline body mass index (<24 vs. ≥24 kg/m ; P-interaction = 0.012), or higher baseline waist circumference (<80 vs. ≥80 cm; P-interaction = 0.032).

Conclusions: Our study suggested that higher baseline UA was significantly associated with increased risk of new-onset diabetes in hypertensive Chinese women, but not in men. Further prospective studies are required to validate the differential association by sex.
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http://dx.doi.org/10.1111/dom.14072DOI Listing
September 2020

Association between plasma retinol levels and the risk of all-cause mortality in general hypertensive patients: A nested case-control study.

J Clin Hypertens (Greenwich) 2020 05 30;22(5):906-913. Epub 2020 Apr 30.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.

To evaluate the association between plasma retinol levels with all-cause mortality and investigate the possible effect modifiers in general hypertensive patients with no previous cardiovascular disease (CVD). This case-control study was nested in the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, controlled trial conducted in 32 communities in Anhui and Jiangsu provinces in China. The current study included 617 cases of all-cause mortality and 617 controls matched on age (≤1 year), sex, treatment group, and study site. All-cause mortality was the main outcome in this analysis, which included death due to any reason. The median follow-up duration was 4.5 years. Overall, there was a U-shaped relation of plasma retinol with all-cause mortality. In the threshold effect analysis, the risk of all-cause mortality significantly decreased with the increase in plasma retinol (per 10 μg/dL increments: OR, 0.73; 95% CI: 0.61-0.87) in participants with plasma retinol <58.3 μg/dL and increased with the increase in plasma retinol (per 10 μg/dL increments: OR, 1.08; 95% CI: 1.01-1.16) in those with plasma retinol ≥58.3 μg/L. In participants with plasma retinol <58.3 μg/dL, a stronger inverse association was observed in those with higher time-averaged SBP (≥140 vs <140 mm Hg; P-interaction = .034), or higher vitamin E levels (≥11.5 [quartile 4]; vs <11.5 μg/mL; P-interaction = .013). The present study demonstrated that there was a U-shaped relationship of plasma retinol levels with the risk of all-cause mortality in general hypertensive patients, with a turning point around 58.3 μg/dL.
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http://dx.doi.org/10.1111/jch.13866DOI Listing
May 2020

Association of brachial-ankle pulse wave velocity and carotid plaque in Chinese hypertensive adults: effect modification by age.

Hypertens Res 2020 08 17;43(8):808-816. Epub 2020 Apr 17.

Department of Cardiology, Peking University First Hospital, 100034, Beijing, China.

We aimed to investigate the association of brachial-ankle pulse wave velocity (baPWV) with carotid plaque presence and carotid plaque number in a Chinese hypertensive population. A total of 13,554 hypertensive subjects from the China Stroke Primary Prevention Trial (CSPPT) were recruited. Arterial stiffness and carotid plaque were evaluated by baPWV and B-mode ultrasonography, respectively. Multivariate logistic regression analysis was used to determine the correlation of baPWV and carotid plaque presence. Multinomial logistic regression analysis was used to determine the correlation of baPWV and carotid plaque number. Further interactions between baPWV and carotid plaque presence were examined using subgroup analysis. Continuous baPWV was positively correlated with carotid plaque presence (OR = 1.05, 95% CI: 1.04-1.07) and carotid plaque number (one- to two-plaque group: OR = 1.04, 95% CI: 1.02-1.06; three-or-more-plaque group: OR = 1.09, 95% CI: 1.07-1.12). When baPWV was classified into quartiles, with the lowest quartile as reference, the ORs for having one, two, or three or more plaques increased in parallel with the quartiles of baPWV, indicating a dose-dependent effect. In a subgroup analysis, the association of baPWV and carotid plaque presence was more pronounced among younger participants (OR: 1.14 vs. 1.06 and 1.03 for the age groups <60 years, 60 ≤ 70 years, and ≥70 years, respectively, P for interaction <0.001). In a Chinese hypertensive population, baPWV was positively associated with carotid plaque presence and carotid plaque number. A more pronounced positive association between baPWV and carotid plaque presence was observed in younger participants.
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http://dx.doi.org/10.1038/s41440-020-0432-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363666PMC
August 2020

Plasma magnesium and the risk of new-onset hyperuricaemia in hypertensive patients.

Br J Nutr 2020 Mar 26:1-8. Epub 2020 Mar 26.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing100083, People's Republic of China.

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.
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http://dx.doi.org/10.1017/S0007114520001099DOI Listing
March 2020

Relationship of Body Mass Index and Waist Circumference With Risk of New-Onset Proteinuria in Hypertensive Patients.

J Clin Endocrinol Metab 2020 03;105(3)

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Context: The association of the combination of body mass index (BMI) and waist circumference (WC) with the risk of proteinuria has previously not been comprehensively investigated and results have been inconclusive.

Objective: To examine BMI and WC in relation to new-onset proteinuria in Chinese hypertensive patients.

Design And Setting: Post hoc analysis of the renal substudy of the China Stroke Primary Prevention Trial (CSPPT).

Patients: 10 805 hypertensive patients without proteinuria at baseline.

Main Outcome Measure: The primary outcome was new-onset proteinuria, defined as a urine dipstick protein reading ≥ 1 + at the exit visit, after a median follow-up duration of 4.4 years.

Results: When analyzed separately, increased BMI (≥ 28 kg/m2, quartile 4; odds ratio [OR], 1.36; 95% confidence interval [CI], 1.08-1.72), or increased WC (≥ 91cm for females, quartile 4; OR, 1.35; 95% CI, 1.01-1.80; and ≥ 79 cm for males, quartile 2-4; OR, 1.60; 95% CI, 1.03-2.50) were each significantly associated with higher risk of new-onset proteinuria. When analyzed jointly, participants without increased BMI and increased WC had the lowest risk, while those with both increased BMI and increased WC had the highest risk of proteinuria (OR, 1.61; 95% CI, 1.21-2.13). Notably, participants with only increased WC also had significantly increased risk of proteinuria (OR, 1.39; 95% CI, 1.04-1.85).

Conclusion: In Chinese hypertensive patients, increased BMI and increased WC were individually and jointly associated with a higher risk of new-onset proteinuria, underscoring the value of monitoring both BMI and WC in assessing proteinuria risk.
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http://dx.doi.org/10.1210/clinem/dgaa026DOI Listing
March 2020