Incidence and mortality of acute kidney disease following coronary angiography: a cohort study of 9223 patients.

PURPOSE: Acute kidney disease (AKD) is an important state in the evolving kidney diseases. However, there is limited data on the incidence and prognosis of AKD following coronary angiography (CAG). Therefore, we aim to characterize the incidence and prognosis of AKD across a large population of CAG patients. METHODS: The consecutive patients with baseline and following measurement of serum creatinine (Scr) between 7 and 90 days after CAG procedure were included. The AKD was defined as a decrease in glomerular filtration rate by > 35%, or an increase in Scr of > 50% (from 7 to 90 days). Survival curves, univariate and multivariable cox regressions were used to assess the association between AKD and mortality. RESULTS: Among 9223 patients (male, 60.3%, mean age, 61.7 ± 9.6), 1540 had AKD. During a median follow-up of 5.4 (IQR 2.2-8.6) years, 1562 (16.9%) patients died. The mortality among the patients with AKD was higher than the non-AKD group (24.8% vs. 15.4%, p < 0.001). AKD was independently associated with a significantly increased risk of all-cause mortality (adjusted hazard ratio [aHR], 1.57; 95% CI 1.39-1.78; p < 0.001). CONCLUSIONS: Our study suggested that AKD is commonly observed after CAG and increased half mortality risk than those without AKD. More attention needs to be paid to patients suffering from AKD.

Malnutrition in patients with coronary artery disease: Prevalence and mortality in a 46,485 Chinese cohort study.

BACKGROUND AND AIMS: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its long-term prognostic impact in general coronary artery disease (CAD) patients is not well known. We aim to report the prevalence and long-term mortality of malnutrition in the whole general population. METHODS AND RESULTS: In this retrospective cohort study, the controlling nutritional status (CONUT) score was applied to 46,485 consecutive patients undergoing coronary angiography (CAG) and diagnosed with CAD from January 2007 to July 2018. Patients were stratified as having no malnutrition (n = 19,780), mild (n = 21,092), moderate (n = 5286) and severe malnutrition (n = 327), based on CONUT score. Overall, mean age was 63.1 ± 10.7 years, and 75.8% of patients (n = 35,250) were male. 45.4% of patients were mildly malnourished and 12.1% were moderately or severely malnourished. During a median follow-up of 5.1 years (interquartile range: 3.0-7.7 years), 6093 (17.3%) patients died. After adjusting for confounders, malnutrition risk was associated with significantly increased risk for all-cause death (mild vs. normal, HR = 1.19,95% confidence interval [CI]: 1.12 to 1.28; moderate vs. normal, HR = 1.42,95% CI: 1.30 to 1.55; severe vs. Normal, HR = 1.95, 95% CI: 1.57 to 2.41) (p for trend<0.001). The similar result on all-cause mortality was also found in different subgroups stratified by gender, chronic kidney disease, anemia, percutaneous coronary intervention. CONCLUSIONS: Malnutrition is a common complication among patients with CAD, and is strongly associated with increased mortality. Further studies need to explore the efficacy of nutritional interventions on long-term prognosis among CAD patients. This study was registered at Clinicaltrials.gov as NCT04407936.

Non-HDL cholesterol paradox and effect of underlying malnutrition in patients with coronary artery disease: A 41,182 cohort study.

BACKGROUND & AIMS: Non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C) were established as the target for blood lipid management among patients with coronary artery disease (CAD). Previous study reported a negative relation between baseline LDL-C levels and long-term prognosis. However, the association between baseline non-HDL-C concentration and clinical outcomes is unknown. METHODS: A total of 41,182 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (non-HDL-C < 2.2 mmol/L, n = 3236; non-HDL-C ≥ 2.2 mmol/L, n = 37,946). The Kaplan-Meier method, Cox regression analyses and restricted cubic splines were used to assess the association between non-HDL-C levels and long-term all-cause mortality. RESULTS: The overall mortality was 12.74% (n = 5247) over a median follow-up period of 5.20 years. Kaplan-Meier analysis showed that low non-HDL-C levels were paradoxically associated with a worse prognosis. After adjustment for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that low non-HDL-C levels (<2.2 mmol/L) were not significantly associated with all-cause mortality (adjusted HR, 1.03; 95% CI, 0.93-1.14). After adjustment for nutritional status, the risk of all-cause mortality in patients with low non-HDL-C levels decreased (adjusted HR, 0.86; 95% CI, 0.78-0.95). In the final multivariate Cox model adjusting for full covariates, low non-HDL-C level was related to better prognosis (adjusted HR, 0.88; 95% CI, 0.80-0.98). CONCLUSION: This study found a paradoxical association between baseline non-HDL-C concentration and long-term all-cause mortality. Malnutrition mainly mediates to the non-HDL-C paradox. Elevated non-HDL-C concentration is still a risk factor of long-term all-cause mortality after considering nutritional status.

Independent and joint effects of high-sensitivity c-reactive protein and hypoalbuminemia on long-term all-cause mortality among coronary artery disease: a prospective and multicenter cohort study.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) plays an important role in hypoalbuminemia as a representative of inflammation, which is closely associated with poor prognosis among patients with coronary artery disease (CAD). The present study aimed to evaluate the independent and joint effects of high hs-CRP levels and hypoalbuminemia on long-term mortality among CAD patients. METHODS: A total of 1449 CAD patients were included from a prospective, multicenter, observational cohort study (REICIN, NCT01402232) of patients referred for coronary angiography (CAG). The primary endpoint was long-term all-cause death. RESULTS: During a median follow-up of 2.9 (2.0-3.0) years, a total of 107 (7.4%) patients died. The long-term mortality was higher among CAD patients with high hs-CRP levels (> 3 mg/L) than those with the low hs-CRP levels (≤ 3 mg/L; 10.7% versus 4.1%; hazard ratio [HR] 2.49; 95% confidence interval [CI] 1.48-4.17). Similarly, CAD patients with hypoalbuminemia had higher mortality than those without hypoalbuminemia (12.2% versus 4.9%; HR 1.93; 95% CI 1.20-3.08). When hs-CRP and albumin were combined, CAD patients with high hs-CRP levels (> 3 mg/L) and with hypoalbuminemia were at the highest risk of death compared with their reference group (hs-CRP ≤ 3 mg/L and albumin > 35 g/L; HR 3.79; 95% CI 1.91-7.52). CONCLUSIONS: High hs-CRP levels and hypoalbuminemia were independently and jointly associated with long-term mortality among CAD patients. Patients with high hs-CRP levels and hypoalbuminemia had the highest risk of long-term mortality compared with other groups.

Association of Lipoprotein(a)-Associated Mortality and the Estimated Glomerular Filtration Rate Level in Patients Undergoing Coronary Angiography: A 51,500 Cohort Study.

Background: High lipoprotein(a) is associated with poor prognosis in patients at high risk for cardiovascular disease. Renal function based on the estimated glomerular filtration rate (eGFR) is a potential risk factor for the change of lipoprotein(a). However, the regulatory effect of eGFR stratification on lipoprotein(a)-associated mortality has not been adequately addressed. Methods: 51,500 patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) were included from the Cardiorenal ImprovemeNt (CIN) study (ClinicalTrials.gov NCT04407936). These patients were grouped according to lipoprotein(a) quartiles (Q1-Q4) stratified by eGFR categories (<60 and ≥60 mL/min/1.73m2). Cox regression models were used to estimate hazard ratios (HR) for mortality across combined eGFR and lipoprotein(a) categories. Results: The mean age of the study population was 62.3 ± 10.6 years, 31.3% were female (n = 16,112). During a median follow-up of 5.0 years (interquartile range: 3.0-7.6 years), 13.0% (n = 6,695) of patients died. Compared with lipoprotein(a) Q1, lipoprotein(a) Q2-Q4 was associated with 10% increased adjusted risk of death in all patients (HR: 1.10 [95% CI: 1.03-1.17]), and was strongly associated with about 23% increased adjusted risk of death in patients with eGFR <60 mL/min/1.73m2 (HR: 1.23 [95% CI: 1.08-1.39]), while such association was not significant in patients with eGFR ≥60 mL/min/1.73m2 (HR: 1.05 [95% CI: 0.97-1.13]). P for interaction between lipoprotein(a) (Q1 vs. Q2-Q4) and eGFR (≥60 vs. eGFR <60 mL/min/1.73m2) on all-cause mortality was 0.019. Conclusions: Elevated lipoprotein(a) was associated with increased risk of all-cause mortality and such an association was modified by the baseline eGFR in CAG patients. More attention should be paid to the patients with reduced eGFR and elevated lipoprotein(a), and the appropriate lipoprotein(a) intervention is required.

Prevalence and prognostic significance of malnutrition in diabetic patients with coronary artery disease: a cohort study.

BACKGROUND: Malnutrition is associated with poor prognosis in cardiovascular disease patients or in diabetic patients. However, the relationship between malnutrition and clinical outcomes in diabetic patients with coronary artery disease (CAD) is not well known. The aim of this study is to report the prevalence and prognostic consequences of malnutrition in diabetic patients with CAD. METHODS: In this retrospective observational study, the Controlling Nutritional Status (CONUT) score applied to 12,898 consecutive diabetic patients with CAD. The association between malnutrition and long-term all-cause mortality was examined using Cox proportional hazards regression analysis. RESULTS: According to CONUT score, 60.5% patients suffered from malnutrition; 46.4%, 13.2%, and 0.9% patients had mild, moderate, and severe malnutrition, respectively. During a median follow-up of 4.88 (2.83-7.51) years, 1973 (15.3%) patients died. After adjustment for confounders, malnutrition was associated with significantly increased risk for long-term all-cause mortality (adjusted hazard ratio for mild malnutrition and moderate to severe malnutrition, respectively: 1.38 [95% confidence interval (CI) 1.07-1.77]; P value = 0.012 and 1.63 [95% CI 1.18-2.24]; P value = 0.003). A similar association was observed around subgroups. CONCLUSIONS: Malnutrition is common in diabetic patients with CAD and is strongly associated with increased mortality. It is necessary to adequately assess the nutritional status and take the effective nutritional guidance to improve the prognosis of diabetic patients with CAD.

Mild Malnutrition Contributes the Greatest to the Poor Prognosis in Coronary Artery Disease With Well-Controlled Low-Density Lipoprotein Cholesterol Levels: A 4,863 Chinese Cohort Study.

Background: Previous studies reported that patients with coronary artery disease (CAD) and well-controlled baseline LDL-C (<1.8 mmol/L) still had higher long-term all-cause mortality. However, no study has been conducted to explore the independent risk factors for long-term mortality. In addition, there also was no study evaluating the population attributable risk (PAR) of independent risk factors in combination with their prevalence and relative risk. Therefore, we aimed to identify the independent risk factors and estimate their PAR in patients with CAD and well-controlled baseline LDL-C (<1.8 mmol/L). Methods: We analyzed 4,863 consecutive CAD patients with well-controlled baseline LDL-C admitted to Guangdong Provincial People's Hospital in China from January 2007 to December 2018. Independent risk factors for long-term all-cause death were evaluated through stepwise approach and multivariable Cox regression analysis. PAR of independent risk factors was calculated with their hazard ratio and prevalence among our cohort. Results: The overall mortality was 16.00% (n = 778) over a median follow-up period of 5.93 years. Independent risk factors for all-cause death included malnutrition, age ≥75 years, congestive heart failure (CHF), chronic kidney disease (CKD) and atrial fibrillation. Among these risk factors of interest, the hazard ratio (HR) of severe malnutrition was the highest (HR 2.82, 95% CI: 1.86-4.26), and the PAR of mild malnutrition was the highest (19.49%, 95% CI: 0.65-36.01%). Conclusion: Malnutrition, age ≥75 years, CHF, CKD and atrial fibrillation were independent predictors for long-term all-cause mortality in CAD patients with well-controlled LDL-C levels. Considering prevalence of these risk factors, more attention should be paid to the occurrence of mild malnutrition for these patients. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04407936.

Prevalence and Mortality of Hypochloremia Among Patients with Coronary Artery Disease: A Cohort Study.

PURPOSE: Hypochloremia is a predictor for short-term mortality in patients with cardiovascular disease, but its association with coronary artery disease (CAD) is still unclear. We aimed to assess the impact of hypochloremia on all-cause mortality (short-and long-term) among patients with CAD. PATIENTS AND METHODS: Based on the registry at Guangdong Provincial People's Hospital in China, we analyzed data of 49,025 hospitalized patients who underwent coronary angiography (CAG) and were diagnosed with CAD from January 2007 to December 2018. To assess the association between hypochloremia and the study endpoints, a logistic-regression model (for 30-day all-cause mortality) and a Cox regression model (for long-term all-cause mortality) were fitted. RESULTS: Overall, 4.4% of the study population showed hypochloremia (<98 mmol/L). During a median follow-up of 5.2 (3.1-7.8) years, a total of 6486 (13.2%) patients died. Patients with hypochloremia were generally older and at risk for diabetes, cardiorenal dysfunction, and morbidity than those without hypochloremia. After adjustment for confounders, hypochloremia remained a significant predictor of mortality risk (30-day all-cause death: adjusted odds ratio [aOR], 1.99; 95% confidence interval, 1.08-3.18; P=0.017 and long-term all-cause death: adjusted hazard ratio [aHR], 1.32; 95% confidence interval, 1.19-1.47; P<0.001). CONCLUSION: Hypochloremia is mildly common in patients with CAD and is associated with increased short-and long-term mortality. Meanwhile, it is necessary to further investigate effective and preventive measures and the potential mechanisms of hypochloremia in patients with CAD.

Malnutrition affects cholesterol paradox in coronary artery disease: a 41,229 Chinese cohort study.

BACKGROUND: Several studies have found that a low baseline low -density lipoprotein cholesterol (LDL-C) concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which is called the "cholesterol paradox". Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. The aim of this study was to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition. METHOD: A total of 41,229 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (LDL-C < 1.8 mmol/L, n = 4863; LDL-C ≥ 1.8 mmol/L, n = 36,366). The Kaplan-Meier method and Cox regression analyses were used to assess the association between LDL-C levels and long-term all-cause mortality and the effect of malnutrition. RESULT: In this real-world cohort (mean age 62.9 years; 74.9% male), there were 5257 cases of all-cause death during a median follow-up of 5.20 years [interquartile range (IQR): 3.05-7.78 years]. Kaplan-Meier analysis showed that low LDL-C levels were associated with a worse prognosis. After adjusting for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that a low LDL-C level (< 1.8 mmol/L) was not significantly associated with all-cause mortality (adjusted HR, 1.04; 95% CI, 0.96-1.24). After adjustment for nutritional status, the risk of all-cause mortality in patients with low LDL-C levels decreased (adjusted HR, 0.90; 95% CI, 0.83-0.98). In the final multivariate Cox model, a low LDL-C level was related to better prognosis (adjusted HR, 0.91; 95% CI, 0.84-0.99). CONCLUSION: This study demonstrated that the cholesterol paradox existed in CAD patients but disappeared after accounting for the effects of malnutrition.

U-shaped association between serum albumin and development of chronic kidney disease in general hypertensive patients.

BACKGROUND & AIMS: We aimed to examine the association between serum albumin (SAlb) and the development of chronic kidney disease (CKD), and examine any possible effect modifiers in general hypertensive patients with normal renal function and with no previous cardiovascular diseases (CVD). METHODS: This is a post-hoc analysis (performed at May, 2018) of 12,621 hypertensive adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and SAlb ≥35.0 g/L from the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT), conducted from May 2008 to August 2013. The primary outcome was development of CKD, defined as a decrease in eGFR of ≥30% and to a level of <60 mL/min/1.73 m2; or end stage renal disease. RESULTS: The median follow-up duration was 4.4 years. Overall, the association between SAlb levels and risk of the primary outcome followed a U-shape. The risk of CKD development significantly decreased with the increment of SAlb (per g/L: OR = 0.92; 95% CI: 0.88-0.96) in participants with SAlb <51.4 g/L, and increased with the increment of SAlb (per g/L: OR = 1.06; 95%CI: 1.01-1.11) in participants with SAlb ≥51.4 g/L. Moreover, in participants with SAlb <51.4 g/L, the association between SAlb and CKD development remained significant in participants without proteinuria (per g/L: OR = 0.93; 95% CI: 0.88-0.99). The association between SAlb and CKD development was not significantly modified by age, sex, folic acid treatment, proteinuria, systolic blood pressure (SBP) at baseline and time-averaged SBP during the treatment period (all P-interactions>0.05). CONCLUSIONS: There was a U-shaped association between SAlb levels and risk of CKD development among general hypertensive patients with normal renal function and without CVD, with a turning point at about 51.4 g/L.

Electrocardiographic-left ventricular hypertrophy and incident stroke among Chinese hypertensive adults.

The relationship between electrocardiographic-left ventricular hypertrophy (ECG-LVH) and stroke has been well established in the Western population with limited information in the Chinese population. This study evaluated the association between ECG-LVH and stroke outcome. A total of 19,815 (95.7%) subjects from the China Stroke Primary Prevention Trial (CSPPT) with baseline ECG were included. ECG-LVH by sex-unspecific Sokolow-Lyon criteria was detected in 1599 participants (8.1%) at baseline. After a mean follow-up of 4.5 years, 605 (3.1%) subjects were detected with new-onset stroke over the total population, baseline ECG-LVH was present in 72 (4.5%) of them during follow-up. After adjusting for various cofounders, ECG-LVH remained as an independent risk factor for stroke events in the total population (HR = 1.43; 95% CI, 1.10-1.84; P = 0.007) and male population (HR = 1.47; 95% CI, 1.07-2.03; P = 0.019). Subgroup analysis showed that baseline ECG-LVH was a risk factor for stroke in individuals younger than 65 years of age(HR = 1.80, 95% CI, 1.31-2.47 vs. HR = 1.02, 95% CI, 0.66-1.59, P value for interaction = 0.047). In summary, LVH diagnosed by ECG is associated with an excess risk for stroke in Chinese hypertensive population, especially in the age group of younger than 65 years.

Serum Lipids and Risk of Rapid Renal Function Decline in Treated Hypertensive Adults With Normal Renal Function.

BACKGROUND: We aim to evaluate the effect of different lipids parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), the TG to HDL-C (TG:HDL-C) ratio, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), on the risk of rapid renal function decline and examine any possible effect modifiers in general hypertensive patients with normal renal function. METHODS: A total of 12,549 hypertensive patients with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 in the renal sub-study of the China Stroke Primary Prevention Trial were included in the analyses. The primary outcome was rapid renal function decline, defined as an average decline in eGFR ≥ 5 ml/min/1.73 m2 per year. RESULTS: The median treatment duration was 4.4 years. After the full adjustment for TC, TG, HDL-C, and other major covariates, a significantly higher risk of rapid renal function decline was found in participants with higher TG [≥150 vs. <150 mg/dl, 7.7% vs. 5.5%; odds ratios (OR): 1.27; 95% confidence interval (CI): 1.06-1.51], higher TG:HDL-C ratio [≥2.7 (median) vs. <2.7, 7.7% vs. 5.0%; OR: 1.39; 95% CI: 1.14-1.71), lower TC (≥200 vs. <200 mg/dl, 6.0% vs. 7.0%; OR: 0.79; 95% CI: 0.67-0.93), or lower LDL-C levels (≥130 vs. <130 mg/dl, 6.1% vs. 7.0%; OR: 0.79; 95% CI: 0.67-0.94). Moreover, the increased risk of the primary outcome associated with elevated TG was particularly evident among individuals with lower total homocysteine levels [<12.4 (median) vs. ≥ 12.4 µmol/l, P interaction = 0.036]. CONCLUSIONS: Higher TG and TG:HDL-C ratio were independent risk factors for rapid renal function decline in hypertensive adults with normal renal function.

Plasma retinol and the risk of first stroke in hypertensive adults: a nested case-control study.

Background: Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited. Objectives: We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods: The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. 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 median treatment duration was 4.5 y. Results: There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-µg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2-4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (<10 compared with ≥10 µmol/L; P-interaction = 0.049). However, plasma retinol had no significant effect on first hemorrhagic stroke (per 10-µg/dL increment; OR: 0.98; 95% CI: 0.79, 1.18). Conclusions: Our data showed a significant inverse association between plasma retinol and the risk of first stroke among Chinese hypertensive adults. This study was registered at clinicaltrials.gov as NCT00794885.

BMI is associated with the development of chronic kidney diseases in hypertensive patients with normal renal function.

OBJECTIVE: We aimed to investigate the relationship of BMI and waist circumference with the development of chronic kidney disease (CKD). METHODS: A total of 12 672 hypertensive patients with estimated glomerular filtration rate (eGFR) at least 60 ml/min per 1.73 m from the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT) were included. The primary outcome was the development of CKD, defined as a decrease in eGFR of at least 30% and to a level of less than 60 ml/min per 1.73 m at the exit visit, or end-stage renal disease. A secondary outcome was rapid renal function decline, defined as an average decline in eGFR of at least 5 ml/min/1.73 m per year. RESULTS: Over a median follow-up of 4.4 years, the risk of the primary event (per 1 kg/m increment; OR = 1.07, 95% CI 1.02-1.14) or rapid renal function decline (per 1 kg/m increment; OR = 1.05, 95% CI 1.01-1.08) increased with each increment of BMI. Consistently, compared with those with normal weight (BMI <24.0 kg/m), participants with obesity (BMI ≥28.0 kg/m) had an increased risk of the primary event (OR = 1.82; 95% CI 1.15-2.90) and rapid renal function decline (OR = 1.26; 95% CI 0.95-1.67). However, waist circumference had no obvious effect on the risk of the primary event (per 5 cm increment: OR = 0.94, 95% CI 0.85-1.04) or rapid renal function decline (OR = 0.96, 95% CI 0.90-1.03). CONCLUSION: Higher BMI, but not waist circumference, was significantly associated with an increased risk of CKD development in hypertensive patients with normal kidney function.

Association of total homocysteine with blood pressure in a general population of Chinese adults: a cross-sectional study in Jiangsu province, China.

OBJECTIVES: We aimed to evaluate the relation of total homocysteine (tHcy) concentrations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, and examine the possible modifiers in the association among a general population of Chinese adults. DESIGN: A cross-sectional study. SETTING: The study was conducted within 21 communities in Lianyungang of Jiangsu province, China. PARTICIPANTS: A total of 26 648 participants aged ≥35 years and with no antihypertensive drug use were included in the final analysis. RESULTS: Overall, there was a positive association between tHcy concentrations and SBP (per 5 µmol/L tHcy increase: adjusted ß=0.45 mm Hg; 95% CI 0.29 to 0.61) or DBP levels (per 5 µmol/L tHcy increase: adjusted ß=0.47 mm Hg; 95% CI 0.35 to 0.59). Compared with participants with tHcy <10 µmol/L, significantly higher SBP levels were found in those with tHcy concentrations of 10 to <15 (adjusted ß=0.80 mm Hg; 95% CI 0.32 to 1.28) and ≥15 µmol/L (adjusted ß=1.79 mm Hg; 95% CI 1.20 to 2.37; p for trend <0.001). Consistently, significantly higher DBP levels were found in participants with tHcy concentrations of 10 to <15 (adjusted ß=0.86 mm Hg; 95% CI 0.49 to 1.22) and ≥15 µmol/L (adjusted ß=2.01 mm Hg; 95% CI 1.57 to 2.46; p for trend <0.001), respectively as compared with those with <10 µmol/L. Furthermore, a stronger association between tHcy and SBP (p for interaction=0.009) or DBP (p for interaction=0.067) was found in current alcohol drinkers. CONCLUSION: Serum tHcy concentrations were positively associated with both SBP and DBP levels in a general Chinese adult population. The association was stronger in current alcohol drinkers.

Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke.

BACKGROUND: The role of platelets and important effect modifiers on the risk of first stroke is unknown. OBJECTIVES: This study examined whether low platelet count (PLT) and elevated total homocysteine (tHcy) levels jointly increase the risk of first stroke, and, if so, whether folic acid treatment is particularly effective in stroke prevention in such a setting. METHODS: A total of 10,789 Chinese hypertensive adults (mean age 59.5 years; 38% male, with no history of stroke and myocardial infarction) were analyzed from the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid (n = 5,408) or 10 mg enalapril alone (n = 5,381). The primary endpoint was first stroke. RESULTS: During 4.2 years of follow-up, a total of 371 first strokes occurred. In the enalapril-alone group, the lowest rate of first stroke (3.3%) was found in patients with high PLT (quartiles 2 to 4) and low tHcy (<15 µmol/l); and the highest rate (5.6%) was in patients with low PLT (quartile 1) and high tHcy (≥15 µmol/l) levels. Following folic acid treatment, the high-risk group had a 73% reduction in stroke (hazard ratio: 0.27; 95% confidence interval: 0.11 to 0.64; p = 0.003), whereas there was no significant effect among the low-risk group. CONCLUSIONS: Among Chinese hypertensive adults, the subgroup with low PLT and high tHcy had the highest risk of first stroke, and this risk was reduced by 73% with folic acid treatment. If confirmed, PLT and tHcy could serve as biomarkers to identify high-risk individuals who would particularly benefit from folic acid treatment. (China Stroke Primary Prevention Trial [CSPPT]; NCT00794885).

Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

BACKGROUND AND PURPOSE: We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). METHODS: Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. RESULTS: The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers (P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant (P=0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). CONCLUSIONS: Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Effects of hydration combined with Shenfu injection on contrast-induced acute kidney injury in acute coronary syndrome patients undergoing percutaneous coronary intervention.

The aim of the present study was to evaluate the efficacy and safety of the Shenfu injection (SFI) in the prevention of contrast-induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). A single-center prospective and randomized controlled trial was performed and 148 ACS patients undergoing PCI were divided randomly into control (n=74; receiving only 0.9% sodium chloride solution for routine hydration) and intervention (n=74; based upon routine hydration and receiving SFI) groups. Serum creatinine (Scr), blood urea nitrogen and urinary neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at the start, and 1 and 2 days after PCI. Among the 148 patients, 14 (9.4%) experienced CI-AKI subsequent to the procedure. CI-AKI occurred in 2.7% of the SFI group and 16.2% of the control group (P<0.05). The incidence of CI-AKI was lower in the intervention group when compared with the control. No serious adverse effects were observed in all patients. No differences between the levels of Scr and estimated glomerular filtration rate in the two groups were identified. However, 12 h after PCI, the urinary NGAL level in the control group was significantly higher than that in the SFI group (P<0.05). Thus, hydration combined with SFI was identified to be more effective than hydration with sodium chloride in the prevention of CI-AKI in ACS patients undergoing PCI.

Effect of MTHFR A1298C and MTRR A66G Genetic Mutations on Homocysteine Levels in the Chinese Population: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: The Chinese population typically has inadequate folate intake and no mandatory folic acid fortification. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are the two key regulatory enzymes in the folate/homocysteine (Hcy) metabolism. Hcy has been implicated in the pathogenesis of cardiovascular disease. We conducted a meta-analysis to assess whether the MTHFR gene A1298C and the MTRR gene A66G polymorphisms affect Hcy levels in the Chinese population. METHODS: This analysis included 13 studies with Hcy levels reported as one of the study measurements. Summary estimates of weighted mean differences and 95% confidence intervals (CIs) were obtained using random-effect models. RESULTS: Overall, there were no significant differences in Hcy concentrations between participants with the MTHFR 1298 CC (12 trials, n = 129), AA (n = 2166; ß, -0.51 µmol/L; 95%CI: -2.14, 1.11; P = 0.53), or AC genotype (n = 958; ß, 0.55 µmol/L; 95%CI: -0.72, 1.82; P = 0.40). Consistently, compared to those with the MTRR 66 GG genotype (6 trials, n = 156), similar Hcy concentrations were found in participants with the AA (n = 832; ß, -0.43 µmol/L; 95%CI: -1.04, 0.17; P = 0.16) or AG (n =743; ß, -0.57 µmol/L; 95%CI: -1.46, 0.31; P = 0.21) genotype. Similar results were observed for the dominant and recessive models. CONCLUSIONS: Neither the MTHFR A1298C polymorphism nor the MTRR A66G polymorphism affects Hcy levels in the Chinese population.

Expression of neutrophil gelatinase-associated lipocalin in low osmolar contrast-induced nephropathy in rats and the effect of N-acetylcysteine.

Serum creatinine (Scr), which is a conventional indicator of contrast-induced nephropathy (CIN), is unable to reflect the damage of kidney promptly. The present study aimed to investigate the value of neutrophil gelatinase-associated lipocalin (NGAL) in kidney and serum of CIN rats to observe whether NGAL can be used as a superior indicator of CIN. Furthermore, N-acetylcysteine (NAC) was used to assess its effect on CIN. A total of 120 adult male Sprague Dawley rats were randomly divided into four groups (n=30/group): CIN rats (CIN), normal rats treated with NAC (NAC), CIN rats treated with NAC (NAC+CIN) and the control group (CON). Serum Scr and NGAL values were measured at 2, 12, 24, 48 and 72 h following the procedure. Immunohistochemistry and western blot analysis were used to detect NGAL within the kidney tissue. Hematoxylin and eosin staining were used to access the renal injury score. Oxidative stress within the kidney was analyzed via malondialdehyde (MDA) and superoxide dismutase (SOD). The level of NGAL in the serum and tissue of the CIN group increased significantly 2 h after the procedure (P<0.05). However, the Scr value did not exhibit a significantly change until 48 h later. Based on the renal injury scores, NAC reduced the kidney damage caused by the contrast. NAC treatment was associated with a decrease in SOD levels and an increase in MDA. These findings suggested that NGAL was a superior indicator of CIN than Scr, as NGAL was able to detect kidney damage much earlier. Furthermore, NAC treatment inhibited oxidative stress, thus protecting against CIN.