Sex-related association of modifiable risk factors with hypertension: A national cross-sectional study of NHANES 2007-2018.

OBJECTIVE: Sex difference is commonly observed in hypertension. We aimed to assess sex differences in the associations of modifiable lifestyle and metabolic risk factors with risk of hypertension. DESIGN: National cross-sectional population study. SETTING: Data from the 2007 to 2018 National Health and Nutrition Examination Survey. PARTICIPANTS: 7087 adults aged ≥30 years without a prior history of hypertension. PRIMARY AND SECONDARY OUTCOME MEASURES: Odds ratios and population attributable fraction (PAF) of hypertension associated with 10 modifiable risk factors: five lifestyle risk factors (current smoking, excess alcohol intake, poor diet, physical inactivity, and unhealthy sleep), and five metabolic risk factors (obesity, diabetes, dyslipidaemia, hyperuricemia, and chronic kidney disease) in women versus men. RESULTS: Compared with women, men had 84% increased risk of prevalence of hypertension. The sex difference in risk for hypertension is more evident in those aged <60 years (p for interaction <.001). For those aged <60 years the combination of lifestyle risk factors accounted for a PAF of 27.2% in men and 48.8% in women, and the combination of metabolic risk factors accounted for a PAF similarly in men (37.4%) and women (38.2%). For those aged ≥60 years, the PAF of lifestyle risk factors was similar between men and women and the metabolic risk factors accounted for a greater proportion in women (33.0% vs. 14.5% in men). CONCLUSIONS: Sex differences may exist in the relation and attribution of lifestyle and metabolic risk factors to hypertension, which may have implications for implementing sex-specific strategies to prevent hypertension.

Risk of cardiovascular disease, death, and renal progression in diabetes according to albuminuria and estimated glomerular filtration rate.

AIM: We aimed to examine risks of major cardiovascular events (MACEs), renal outcomes, and all-cause mortality in type 2 diabetes mellitus (T2DM) patients with different diabetic kidney disease (DKD) subtypes. METHODS: A total of 36,509 participants with T2DM recruited from 20 community sites across mainland China were followed up during 2011-2016. DKD subtypes were categorized based on albuminuria (urinary albumin-to-creatinine ratio, UACR ≥ 30 mg/g) and reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) as Alb-/eGFR-, Alb+/eGFR-, Alb-/eGFR+, and Alb+/eGFR+. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of developing clinical outcomes in DKD subtypes. RESULTS: More than half (53.5%) of participants with diabetes and reduced eGFR had normal UACR levels (Alb-/eGFR+), termed as non-albuminuria DKD. These patients had a modest increase in the risks of MACEs (hazard ratio, HR 1.42 [95% CI 1.08;1.88]) and mortality (HR 1.42 [1.04;1.92]) compared with patients without DKD, whereas CKD progression was not significantly increased (HR 0.97 [0.60;1.57]). Participants with albuminuria (Alb+/eGFR- or Alb+/eGFR+) had higher risks of clinical outcomes. Subgroup analysis revealed that the associations between non-albuminuria DKD and risks of MACEs and mortality were more evident in those aged <65 years. CONCLUSION: Non-albuminuria DKD accounts for more than half of DKD cases with low eGFR in Chinese diabetes patients. Diabetes patients with albuminuria are at higher risks of developing clinical outcomes and warrant early intervention, as well as patients with non-albuminuria DKD with age < 65 years.

Blood Pressure Levels, Cardiovascular Events, and Renal Outcomes in Chronic Kidney Disease Without Antihypertensive Therapy: A Nationwide Population-Based Cohort Study.

BACKGROUND: High blood pressure (BP) is highly prevalent in patients with chronic kidney disease. However, the thresholds to initiate BP-lowering treatment in this population are unclear. We aimed to examine the associations between BP levels and clinical outcomes and provide evidence on potential thresholds to initiate BP-lowering therapy in people with chronic kidney disease. METHODS: This nationwide, multicenter, prospective cohort study included 12 523 chronic kidney disease participants without antihypertensive therapy in mainland China. Participants were followed up during 2011 to 2016 for cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, hospitalized or treated heart failure, and cardiovascular death) and renal events (≥20% decline in the estimated glomerular filtration rate, end-stage kidney disease, and renal death). RESULTS: Overall, 652 cardiovascular events and 1268 renal events occurred during 43 970 person-years of follow-up. We observed a positive and linear relationship between systolic BP and risks of cardiovascular and renal events down to 90 mm Hg, as well as between diastolic BP and risks of renal events down to 50 mm Hg. A J-shaped trend was noted between diastolic BP and risks of cardiovascular events, but a linear relationship was revealed in participants <60 years (P for interaction <0.001). A significant increase in the risk of cardiovascular and renal outcomes was observed at systolic BP ≥130 mm Hg (versus 90-119 mm Hg) and at diastolic BP ≥90 mm Hg (versus 50-69 mm Hg). CONCLUSIONS: In people with chronic kidney disease, a higher systolic BP/diastolic BP level (≥130/90 mm Hg) is significantly associated with a greater risk of cardiovascular and renal events, indicating potential thresholds to initiate BP-lowering treatment.

Examining the Linear Association Between Blood Pressure Levels and Cardiovascular Diseases in the Absence of Major Risk Factors in China.

BACKGROUND: Many studies demonstrate a J-shaped association between blood pressure and cardiovascular diseases (CVDs), but the findings are plagued by confounding from other traditional cardiovascular risk factors (CVRFs). Our aims were to examine the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels with CVD in individuals without major CVRFs and whether there were thresholds for the association. METHODS: In the 4C study (China Cardiometabolic Disease and Cancer Cohort), 36 042 CVRF-free participants without CVD, diabetes, dyslipidemia, hypertension, or smoking were identified during 2011 to 2012. Among CVRF-free participants, 17 476 CVRF-preferable individuals with better glycemic (fasting glucose, <110 mg/dL; 2-hour post-load glucose, <140 mg/dL) and lipid profile (total cholesterol, <200 mg/dL; LDL [low-density lipoprotein] cholesterol, <130 mg/dL) were selected. The total person-years of follow-up for CVRF-free subjects and CVRF-preferable subjects were 130 147 and 63 573 person-years, respectively. Information on the development of major CVDs was collected during 2014 to 2016. Cox proportional hazard models were performed to estimate the risks for incident CVD by SBP and DBP groups, respectively. RESULTS: We found that both baseline SBP and DBP presented significantly linear associations with CVD risks in CVRF-free and CVRF-preferable participants. There is significant increase in the CVD risk among CVRF-free participants with baseline SBP level of 110 to 119 mm Hg (hazard ratio, 1.79 [95% CI, 1.19-2.71]), 120 to 129 mm Hg (hazard ratio, 2.03 [95% CI, 1.36-3.03]), and 130 to 139 mm Hg (hazard ratio, 2.15 [95% CI, 1.40-3.28]) compared with SBP <110 mm Hg. Significant increases were also observed for DBP level of 80 to 89 mm Hg (hazard ratio, 1.43 [95% CI, 1.03-1.97]) compared with DBP <70 mm Hg. Similar results were observed in CVRF-preferable participants. CONCLUSIONS: SBP and DBP with levels currently considered normal were significantly and linearly associated with incident CVD without thresholds above 110/70 mm Hg among Chinese adults without major CVRFs.

New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse wave velocity and albuminuria: a prospective cohort study.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

Negative Risk Markers for Cardiovascular Risk Evaluation in Chinese Adults.

Background: The atherosclerotic cardiovascular disease (ASCVD) risk predicted by traditional risk factors is used to guide preventive treatment. We aimed to investigate whether preferable levels of non-traditional emerging risk factors (i.e., negative risk markers) could downgrade the predicted ASCVD risk beyond traditional risk factors. Methods: A total of 7,568 Chinese adults aged ≥ 40 years were followed up during 2010-2015. Negative risk markers including non-traditional lipids, urinary albumin-to-creatinine ratio, electrocardiogram (ECG), and measurements of atherosclerosis were evaluated using diagnostic likelihood ratio (DLR) and continuous net reclassification index (NRI) for their ability to downshift predicted CVD risk in the overall study population and in participants with intermediate (traditional risk factor predicted ASCVD risk 7.5% to 19.9%) or high risk (≥20%). Results: During a median follow-up of 4.5 years, 416 participants developed CVD events including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Among negative risk markers examined, lipoprotein(a) ≤ 10th percentile (5 mg/dL), normal ECG, and carotid intima-media thickness (CIMT) ≤ 25th percentile (0.5 mm) provided moderate CVD risk reclassification and downward changes in pre- to post-test risk on top of the traditional CVD risk factors, especially in high-risk participants. The DLRs were 0.41, 0.75, and 0.41, and the NRIs were 18, 22, and 14% for lipoprotein(a), ECG, and CIMT, respectively in high-risk participants. Conclusions: Lipoprotein(a) ≤ 5 mg/dL, normal ECG, and CIMT ≤ 0.5 mm might be used as negative non-traditional risk markers to correctly downgrade predicted ASCVD risk in Chinese adults.

Hypertension Defined by 2017 ACC/AHA Guideline, Ideal Cardiovascular Health Metrics, and Risk of Cardiovascular Disease: A Nationwide Prospective Cohort Study.

BACKGROUND: The updated definition of hypertension by the American College of Cardiology (ACC) and the American Heart Association (AHA) is an important paradigm shift and has lead to extensive discussion. We aimed to examine the association between the updated blood pressure (BP) categories and the risk of cardiovascular diseases (CVDs) with potential modifications from other cardiovascular health metrics (CVHMs). METHODS: This prospective study included 91,204 participants ≥40 years recruited from 20 community sites across mainland China. Participants were followed up during 2010-2016 for CVD events including nonfatal myocardial infarction, stroke, heart failure, and cardiovascular death. BP categories were defined according to the 2017 ACC/AHA guideline and CVHMs included smoking, physical activity, diet, body-mass index, total cholesterol, and fasting glucose. FINDINGS: Overall, 1,985 major CVD events occurred during a mean follow-up of 3.7 years. Having more ideal CVHMs significantly reduced the risk of CVD events in both stage 1 and stage 2 hypertension. Compared with participants without hypertension, participants having ≥4 ideal CVHMs were no longer associated with an increased CVD risk in stage 1 hypertension (HR=1·04; 95% CI=0·83-1·31), but less so in stage 2 hypertension (HR=1·90, 95% CI=1·70-2·13). Such pattern of association was more evident in participants aged <60 years (P for interaction <0·05). INTERPRETATION: Stage 1 hypertension defined by the ACC/AHA identifies individuals at increased CVD risk, which can be attenuated by achieving more preferable cardiovascular health, especially in adults aged <60 years.

Genetic susceptibility, family history of diabetes and healthy lifestyle factors in relation to diabetes: A gene-environment interaction analysis in Chinese adults.

AIMS/INTRODUCTION: To analyze the associations and interactions of the genetic susceptibility and family history of diabetes with lifestyle factors in relation to diabetes among Chinese adults. MATERIALS AND METHODS: We constructed a genetic risk score of 34 single-nucleotide polymorphisms in 11,596 participants from Songnan and Youyi communities, Baoshan District, Shanghai, China. We determined a healthy lifestyle by a normal body mass index (<24 kg/m2 ), adequate fruit and vegetable intake (≥4.5 cups/day), never smoked or quit smoking >1 year prior, sufficient physical activity (≥600 metabolic equivalent minutes per week), and a sleep duration of ≥6 to ≤8 h/day. Logistic regression models were used to examine the associations and interactions between heritability and lifestyle on diabetes. RESULTS: A healthier lifestyle was associated with a lower prevalence of diabetes within any heritable risk groups categorized by the genetic risk score and family history of diabetes. In the combined communities, the odds ratio (95% confidence interval) for diabetes associated with each additional healthy lifestyle factor was 0.83 (0.77-0.89) among participants with a low genetic risk score and 0.86 (0.81-0.91) among participants with a high genetic risk score (Pinteraction = 0.66). Similar interaction patterns of family history (Pinteraction = 0.15) and the combination of family history and the genetic risk score with healthy lifestyle (Pinteraction = 0.55) on diabetes were observed. CONCLUSIONS: A healthier lifestyle was associated with a significantly lower prevalence of diabetes regardless of heritable risk groups, highlighting the importance of adhering to a healthy lifestyle for diabetes prevention among the entire population.

The progression and regression of metabolic dysfunction-associated fatty liver disease are associated with the development of subclinical atherosclerosis: A prospective analysis.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed and diagnosed based on modified criteria. However, evidence for the risks of developing subclinical atherosclerosis with MAFLD transitions according to its new definition has never been reported. METHODS: Using data from a community-based cohort, 6232 participants aged 40 years or older were included and were followed up for a median of 4.3 years during 2010-2015. Participants were categorized into four groups (stable non-MAFLD, MAFLD regressed to non-MAFLD, non-MAFLD progressed to MAFLD, and stable MAFLD). Subclinical atherosclerosis was defined as elevated carotid intima-media thickness (CIMT), elevated brachial-ankle pulse wave velocity (ba-PWV), or microalbuminuria. RESULTS: Compared with the stable non-MAFLD category, participants who progressed to MAFLD at follow-up visit had a 1.356-fold increased risk of developing elevated CIMT [odds ratio (OR) = 1.356; 95% confidence interval (CI) = 1.134-1.620], and a 1.458-fold increased risk of incident microalbuminuria (OR = 1.458; 95% CI = 1.034-2.056) after adjustment for confounders, respectively. In addition, participants with stable MAFLD showed 17.6%, 32.4%, and 35.4% increased risks of developing elevated CIMT, elevated ba-PWV and microalbuminuria, respectively. Compared with the stable MAFLD category, participants with MAFLD and low probability of fibrosis at baseline who regressed to non-MAFLD at follow-up visit had a 29.4% decreased risk of developing elevated CIMT (OR = 0.706; 95% CI = 0.507-0.984), a 43.1% decreased risk of developing elevated ba-PWV (OR = 0.569; 95% CI = 0.340-0.950), but was not significantly associated with incident microalbuminuria (OR = 0.709; 95% CI = 0.386-1.301). The decreased risks attributed to MAFLD regression were more evident in participants without diabetes or dyslipidemia, as well as in those with 0-1 metabolic risk abnormalities, respectively. CONCLUSIONS: MAFLD was significantly associated with higher risks of developing subclinical atherosclerosis. Moreover, the regression of MAFLD might modify the risks of developing subclinical atherosclerosis, especially among those with low probability of fibrosis or less metabolic risk abnormalities. Since 40% of baseline participants with missing data on MAFLD measurement at follow-up were excluded, the conclusions should be speculated with caution.

The 2017 ACC/AHA stage 1 hypertension is associated with arterial stiffness: a prospective analysis.

OBJECTIVE: To examine the association between stage 1 hypertension defined by the 2017 American College of Cardiology and American Heart Association (ACC/AHA) guideline and risk of developing arterial stiffness. METHODS: During 2010-2015, 4595 adults aged ≥40 years without cardiovascular disease were followed up for a median of 4.3 years. BP levels at baseline were categorized into normal, elevated, stage 1 hypertension, and stage 2 hypertension. The development of arterial stiffness was defined as a normal brachial-ankle pulse wave velocity (ba-PWV) at baseline and an increased ba-PWV at follow-up. RESULTS: Compared with participants with normal BP, participants with stage 1 hypertension had a 1.48-fold increased risk of developing arterial stiffness [odds ratio (OR) =2.48; 95% confidence interval (CI) =1.59-3.85] after adjustment for cardiovascular risk factors. The association was more evident in adults aged 40-59 years (OR =4.08; 95% CI =2.06-8.08) than that in those aged ≥60 years (OR =1.47; 95% CI =0.81-2.67). A systolic BP 130~139 mmHg was significantly associated with arterial stiffness independent of diastolic BP (OR =2.90; 95% CI =1.86-4.52). Stage 1 hypertension either at baseline or at follow-up was associated with increased risks compared with normal BP at both baseline and follow-up. CONCLUSIONS: The 2017 ACC/AHA stage 1 hypertension was significantly associated with higher risks of arterial stiffness.

Urinary albumin-to-creatinine ratio levels are associated with subclinical atherosclerosis and predict CVD events and all-cause deaths: a prospective analysis.

OBJECTIVE: We aimed to examine the associations of urinary albumin-to-creatinine ratio (ACR) levels with risks of subclinical atherosclerosis, cardiovascular events and all-cause deaths. METHODS: Data from a large population-based cohort were used, which included 9580 participants aged ≥40 years free from cardiovascular diseases. Carotid intima-media thickness, brachial-ankle pulse wave velocity and ankle-brachial index were measured at baseline to assess subclinical atherosclerosis. After a median of 4.53 years' follow-up, 486 cardiovascular events and 230 all-cause deaths were recorded. RESULTS: The urinary ACR levels were categorised into three groups. Compared with the normal group (0≤ACR <7.82 mg/g), people with low-grade albuminuria (7.82≤ACR <30 mg/g) and albuminuria (ACR ≥30 mg/g) had higher levels of subclinical atherosclerosis. In prospective analysis, people with low-grade albuminuria was not significantly associated with cardiovascular events (HR=1.18; 95% CI 0.95 to 1.46], whereas people with albuminuria had a 50% higher risk of cardiovascular events (HR=1.50; 95% CI 1.11 to 2.03). People with low-grade albuminuria and albuminuria had 43% (HR=1.43; 95% CI 1.05 to 1.93) and 87% (HR=1.87; 95% CI 1.24 to 2.81) higher risks of all-cause deaths during follow-up, respectively. In stratified analysis, the association of higher ACR with risks of cardiovascular events and all-cause deaths was stronger among individuals with concomitant subclinical atherosclerosis, the presence of diabetes and more cardiovascular risk factors, respectively. CONCLUSIONS: ACR levels were positively associated with subclinical atherosclerosis and predicted the risks of cardiovascular events and all-cause deaths. Evaluation of ACR levels should be integrated into risk stratification and prevention of cardiovascular events and all-cause deaths, especially among those with pre-existing subclinical atherosclerosis and cardiometabolic abnormalities.

The association of low-grade albuminuria with incident non-alcoholic fatty liver disease and non-invasive markers of liver fibrosis by glycaemia status.

BACKGROUND & AIM: Low-grade albuminuria, as an early marker of endothelial dysfunction and kidney damage, has been recognized as a risk factor for metabolic disorders. Epidemiological studies manifesting the association of low-grade albuminuria with the risk of incident NAFLD and fibrosis were not available. We aimed to investigate the association of low-grade albuminuria with incident NAFLD and fibrosis by glycaemia status. METHODS: A prospective population-based study was performed in 3308 participants without NAFLD at recruitment. Baseline urinary albumin excretion was obtained by a first-voided early morning spot urine sample. At follow-up visit, incident NAFLD was diagnosed by hepatic ultrasound after excluding alcohol abuse and other cause of hepatic diseases. Fatty liver index (FLI) was employed to reflect liver fat content. Liver fibrosis was evaluated by NAFLD fibrosis score (NFS), fibrosis-4 score (FIB-4) and Hepamet fibrosis score (HFS) respectively. RESULTS: After 4.3 years of follow-up, 622 (18.8%) were detected as incident NAFLD. Participants with low-grade albuminuria imposed a 40.4% [1.404 (1.112-1.772)] greater risk on incident NAFLD, and 52.0% [1.520 (1.141-2.026)], 87.4% [1.874 (1.291-2.720)] and 40.4% [1.404 (1.038-1.898)] higher risks on newly onset higher values of FLI, NFS and FIB-4 respectively. The effect of low-grade albuminuria was stronger in the subgroup of non-diabetic population. CONCLUSIONS: Low-grade albuminuria was independently associated with incident NAFLD and a higher probability of fibrosis, especially among non-diabetic individuals.

Serum Dickkopf-3 Level Is Inversely Associated with Significant Coronary Stenosis in an Asymptomatic Chinese Cohort.

Dickkopp-3 (DKK3) has been identified to play a protection role against atherosclerosis. However, little is known about the relationship between serum DKK3 levels and subclinical coronary atherosclerosis. We aimed to investigate the association of serum DKK3 with coronary stenosis in an asymptomatic Chinese population. A total of 550 Chinese adults aged 40-60 years and without symptoms or histories of cardiovascular diseases were randomly selected to undergo coronary computed tomography angiography. We defined ≥ 50% luminal narrowing as significant coronary stenosis and measured serum DKK3 levels by an enzyme-linked immunosorbent assay (ELISA). Fifty-nine participants had significant coronary stenosis and 223 had < 50% coronary stenosis. Proportions of significant coronary stenosis were 13.7%, 11.4%, and 7.1% in DKK3 tertiles 1-3, respectively (Ptrend = 0.0427). In the univariable multinomial logistic regression model, a decreasing DKK3 tertile was associated with significant coronary stenosis with borderline significance (OR: 1.40; 95% confidence intervals (CI): 0.98-1.99, P = 0.0642). In the multivariable regression model, participants in the lowest DKK3 tertile were associated with a 1.42-fold increased risk of significant coronary stenosis than those in the highest DKK3 tertile (OR: 2.42; 95% CI: 1.10-5.33; P = 0.0279) after adjustment for conventional cardiovascular risk factors. In addition, associations between DKK3 and significant coronary stenosis were consistent among subgroups. However, no significant association was found between serum DKK3 levels and < 50% coronary stenosis. Therefore, we have added to the existing evidence that serum DKK3 is inversely associated with the risk of significant coronary stenosis in asymptomatic middle-aged Chinese.

The Association and Predictive Ability of ECG Abnormalities with Cardiovascular Diseases: A Prospective Analysis.

Aims: To examine whether electrocardiography (ECG) could provide additional values to the traditional risk factors for cardiovascular disease (CVD) risk prediction among different cardiovascular risk subgroups. Methods: A total of 7,872 community residents aged ≥40 years were followed up for a median of 4.5 years. A 12-lead resting ECG was examined for participants at baseline. CVD events including myocardial infarction, stroke and cardiovascular mortality were collected. Cox proportional hazards models were used and models of traditional risk factors with and without ECG were compared. Results: At baseline, 2,470 participants (31.3%) had ECG abnormalities. During follow-up, 464 participants developed CVD events. ECG abnormalities were associated with an increased risk of CVD after adjustment for the traditional risk factors in participants with a 10-year atherosclerotic CVD (ASCVD) risk ≥10% (hazard ratio, HR: 1.45; 95% confidence interval, CI: 1.11, 1.91). Adding ECG abnormalities to the traditional CVD risk factors improved reclassification for those who did not experience events [net reclassification index: 8.0% (95% CI: 2%, 19.5%)], discrimination (integrated discrimination improvement: 0.7% (95% CI: 0.1%, 1.9%), and calibration (goodness of fit P value from 0.600 to 0.873) in participants with a 10-year ASCVD risk ≥10%. However, no significant association and improvement were found in participants with a 10-year ASCVD risk <10%. Conclusions: ECG screening might provide a marginal improvement in CVD risk prediction in adults at high risk. However, ECG should not be recommended in adults at low risk.

Association of QTc Interval with Risk of Cardiovascular Diseases and Related Vascular Traits: A Prospective and Longitudinal Analysis.

Background: Prolonged heart rate corrected QT (QTc) interval was reported to be associated with cardiovascular diseases (CVDs). Objective: There exists little data on the association between QTc interval and cardiovascular risk in Asian populations. We prospectively investigated the association of QTc interval with CVDs and vascular traits in a large cohort of Chinese adults. Methods: A total of 7,605 participants aged 40 years or older from a well-defined community without CVDs at baseline were included and followed up for an average of 4.5 years. Association of baseline QTc interval with incident CVDs was evaluated using Cox regression analysis. Associations of QTc interval with brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), and risk of microalbuminuria and peripheral arterial diseases (PAD) were secondarily examined. Results: Prolonged QTc interval (≥460 ms in women and ≥450 ms in men) was associated with 51% higher risk of total major CVDs (hazard ratio [HR] = 1.51, 95% confidence interval [CI] [1.20, 1.90]), particularly, 48% increased risk of stroke (95% CI [1.16, 1.88]). Prolonged QTc interval was positively associated with baPWV (ß = 38.10 cm/s, standard error [SE] = 8.04, P < 0.0001) and CIMT (ß = 0.01 mm, SE = 0.01, P = 0.04). Prolonged QTc interval was associated with increased risk of incident microalbuminuria (odds ratio [OR] = 1.65, 95% CI [1.21, 2.24]) and PAD (2.49, 95% CI [1.35, 4.59]). Conclusions: Prolonged QTc interval is positively and significantly associated with increased risk of CVDs and related vascular traits in Chinese population.

A comparative analysis of current blood pressure management guidelines in people with and without diabetes.

Hypertension is the leading global risk factor for cardiovascular disease and premature death. Recommendations from current guidelines of blood pressure (BP) management differ in many ways; therefore, we did an overview and comparative analysis of major clinical guidelines of BP management in people with and without diabetes, including the definition and classification of hypertension, initiation of antihypertensive drug therapy, BP control targets, and antihypertensive treatment strategies. BP management in patients with diabetes was discussed in great detail using both hypertension and diabetes guidelines. We conclude that high-level evidence from high-quality clinical studies is urgently needed to settle uncertainties on BP management recommendations.

Detection of diabetes and prediabetes using glycosylated hemoglobin in Chinese adults living in Shanghai: A prospective analysis.

BACKGROUND: This study aimed to evaluate the discriminative abilities of glycosylated hemoglobin (HbA1c) and to examine the optimal HbA1c cutoff values for diabetes and prediabetes in Chinese adults. METHODS: Data of a population-based cohort of Chinese adults aged ≥40 years living in Jiading District in Shanghai were used. At baseline, 9389 and 7241 participants were included to identify the optimal HbA1c cutoff values for diabetes and prediabetes, respectively using the 1999 World Health Organization criteria as reference. In addition, the follow-up data on incident diabetes of 4538 participants were used to determine the HbA1c cutoff value for prediabetes using the development of diabetes as reference. The discriminative abilities of HbA1c were evaluated using receiver operating characteristic (ROC) curves, and the optimal cutoff values were determined by Youden's index. RESULTS: The areas under the ROC curves were 0.849 for diabetes, 0.614 for prediabetes using baseline data, and 0.648 for prediabetes using follow-up data. An HbA1c cutoff value of 6.0% had the largest Youden's index to diagnose diabetes with a sensitivity of 70.2% and a specificity of 87.4%. An HbA1c cutoff value of 5.6% was indicated for prediabetes using both baseline and follow-up data. However, the sensitivity and specificity were both low (55.4% and 61.1% using an oral glucose tolerance test as reference, 64.6% and 57.1% using incident diabetes as reference). CONCLUSIONS: An HbA1c value ≥6.0% could be used to detect diabetes in Chinese adults aged ≥40 years. However, although an HbA1c value of 5.6% to 5.9% was indicated in this study, the overall discrimination of HbA1c for prediabetes was poor.

Clinicopathological significance of steroidogenic factor-1 expression in ovarian cancer versus ovarian sex cord stromal tumor.

The significance of steroidogenic factor-1 (SF-1) in human ovarian tumor has not been fully investigated. The purposes of this study are to provide a meta-analysis for SF-1 and to determine whether SF-1 is associated with ovarian tumor progression and clinicopathological characteristics. A detailed literature search was made for related research publications written in English. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, and odds ratio (OR) and corresponding confidence intervals (CIs) were calculated and summarized respectively. Final analysis from seven eligible studies was performed. Aberrant SF-1 expression was significantly lower in ovarian cancer compared to that of normal ovarian tissue (OR = 0.02, 95% CI = 0.00-0.16, p = 0.0002). However, SF-1 protein expression was not significantly different between benign and malignant ovarian tumors (p = 0.35). Interestingly, aberrant SF-1 expression was significantly higher in ovarian sex cord stromal tumors than that of ovarian cancer (OR = 0.00, 95% CI = 0.00-0.01, p < 0.00001). The results of this meta-analysis suggest that SF-1 may play an important role in ovarian cancer initiation and progression. Moreover, SF-1 expression may serve as a marker in the differential diagnosis between ovarian sex cord stromal tumors and ovarian cancer.

Upregulated microRNA-199a-5p inhibits nuclear receptor corepressor 1 translation in mice with non­alcoholic steatohepatitis.

Mounting evidence indicates that dysregulated microRNAs (miRNAs) are important in the etiology and pathogenesis of steatohepatitis. However, the functions of miRNAs in the pathophysiological process of non-alcoholic steatohepatitis (NASH) are poorly understood. In this study, C57BL/6J mice were fed a methionine-choline­deficient (MCD) diet for eight weeks in order to induce hepatic steatohepatitis. Using reverse transcription polymerase chain reaction, the hepatic expression levels of miR-199a-5p, miR-122 and miR-221 in the mice were examined. Bioinformatic analysis of dysregulated miR-199a-5p was performed to predict the potential role of miR­199a­5p in NASH. The MCD diet was found to significantly reduce miR-122 expression levels and significantly increase miR­199a-5p expression levels in mouse livers, compared with those of mice fed a control diet. In the bioinformatic analysis, miR­199a­5p was identified to be predominantly involved in transcription, protein serine/threonine kinase activity, insulin signaling, and the Wnt and mitogen­activated protein kinase signaling pathways. The regulation of nuclear receptor corepressor 1 (NCOR1) by miR­199a-5p was also examined by silencing and overexpressing this miRNA in LX-2 cells. The data revealed that NCOR1 protein levels were significantly reduced and enhanced by miR-199a-5p mimic and inhibitor, respectively. These findings suggest a key role for miR-199a-5p in the progression of NASH through inhibition of NCOR1 translation, and provide novel insights into NASH pathogenesis.