Association of Stroke With Metabolic Dysfunction-Associated Fatty Liver Disease With and Without CKD.

RATIONALE & OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD), a risk factor for stroke and all-cause mortality, is highly prevalent among patients with chronic kidney disease (CKD), but it is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We enrolled 95,353 participants from the Kailuan Cohort Study, among whom 35,749 had CKD at baseline or developed CKD during the follow-up period, and 59,604 individuals who had no CKD at baseline or during the follow-up period. EXPOSURE: MAFLD. OUTCOME: Stroke (ischemic stroke, hemorrhagic stroke), all-cause mortality. ANALYTICAL APPROACH: Adjusted Cox regression models were used to estimate the influence of MAFLD on stroke outcomes within the subgroups defined by the presence of CKD. RESULTS: After a median follow-up of 12.8 years, 6,140 strokes (6.4%) and 11,975 deaths from any cause (12.6%) occurred. After adjusting for potential confounders, MAFLD was associated with an increased incidence of stroke among the participants with CKD (HR, 1.34 [95% CI, 1.23-1.45]) but not among those without CKD (HR, 1.05 [95% CI, 0.97-1.15]; Pinteraction<0.001). This association was principally related to ischemic stroke (HR, 1.38 [95% CI, 1.26-1.51]) and not hemorrhagic stroke (HR, 1.04 [95% CI, 0.85-1.26]). No association was found between MAFLD and all-cause mortality in the participants with CKD (HR,1.04 [95% CI, 0.98-1.10]) or those without CKD (HR,1.03 [95% CI, 0.97-1.09]). Among the participants with CKD, compared with non-MAFLD, MAFLD with diabetes (HR,1.36 [95% CI, 1.23-1.50]) or overweight/obesity (HR,1.30 [95% CI, 1.14-1.50]) was associated with a higher risk of stroke whereas MAFLD without overweight/obesity or diabetes was not associated with a higher risk (HR,1.08 [95% CI, 0.81-1.43]). LIMITATIONS: This was an observational study and included individuals with CKD who had a relatively high estimated glomerular filtration rate. CONCLUSIONS: MAFLD was associated with an increased risk of stroke in individuals with CKD but not in those without CKD. PLAIN-LANGUAGE SUMMARY: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is recognized as a risk factor for stroke in the general population, is highly prevalent among individuals with chronic kidney disease (CKD). However, the impact of MAFLD on the risk of stroke in patients with CKD remains uncertain. We investigated the association of MAFLD with stroke in individuals with and without CKD. Our analysis revealed that MAFLD was associated with a significantly increased risk of stroke in individuals with CKD, and the magnitude of this increased risk was greater in the setting of CKD. These findings highlight the need for increased attention to MAFLD in patients with CKD and emphasize that addressing and preventing MAFLD in this population may contribute to reduced morbidity from stroke.

Metabolic syndrome parameters' variability and stroke incidence in hypertensive patients: evidence from a functional community cohort.

BACKGROUND: Stroke is a common complication of hypertension, but the predictive value of metabolic syndrome parameters' variability on stroke risk in individuals with hypertension remains unclear. Therefore, our objective was to investigate the relationship between metabolic syndrome parameters' variability and the risk of total stroke and its subtypes in hypertensive patients. METHODS: This prospective cohort study included 17,789 individuals with hypertension from the Kailuan study since 2006. Metabolic syndrome parameters, including waist circumference (WC), fasting blood glucose (FBG), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), were collected at three follow-up visits in the 2006, 2008, and 2010 surveys. We assess the variability utilizing the coefficient of variation (CV), standard deviation (SD), average real variation (ARV), and variability independent of the mean (VIM), with CV initially assessed. Participants were categorized based on the number of high-variability metabolic syndrome parameters (0, 1, 2, ≥ 3). Stroke cases were identified by reviewing medical records. The associations between variability in metabolic syndrome parameters and the risk of total stroke and its subtypes were analyzed using Cox proportional hazard regression models. RESULTS: During a median follow-up of 9.32 years, 1223 cases of stroke were recorded. Participants with ≥ 3 high-variability metabolic syndrome parameters had an increased risk of total stroke (HR: 1.29, 95%CI 1.09-1.52), as well as an increased risk of ischemic stroke (HR: 1.31, 95%CI 1.05-1.63) compared to those without high-variability parameters. The study also examined variability in each metabolic syndrome parameter, and significant associations with an increased risk of total stroke were observed for variability in SBP (HR: 1.24, 95%CI 1.05-1.46) and HDL-C (HR: 1.34, 95%CI 1.09-1.64). CONCLUSIONS: Long-term fluctuations in metabolic syndrome parameters significantly increase the risk of total stroke, especially ischemic stroke. Maintaining low variability in metabolic syndrome parameters could benefit health, and hypertensive individuals must be regularly monitored.

Supra-additive effect of chronic inflammation and atherogenic dyslipidemia on developing type 2 diabetes among young adults: a prospective cohort study.

BACKGROUND: Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. METHODS: Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). RESULTS: During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP < -0.0699 and CumCRP < 1 mg/L, co-exposure to CumAIP ≥ - 0.0699 and CumCRP ≥ 3 mg/L had a significant hazard ratio (HR) [2.55 (2.23-2.92)] after adjusting for socio-demographic, life-style factors, family history of diabetes, blood pressure, renal function and medication use. The co-exposure-associated risks varied greatly by age distribution (P-interaction = 0.0193): < 40 years, 6.26 (3.47-11.28); 40-49 years, 2.26 (1.77-2.89); 50-59 years, 2.51 (2.00-3.16); 60-69 years, 2.48 (1.86-3.30); ≥ 70 years, 2.10 (1.29-3.40). In young adults (< 45 years), both exposures had a significant supra-additive effect on diabetogenesis (relative excess risk due to interaction: 0.80, 95% CI 0.10-1.50). CONCLUSIONS: These findings highlight the need for age-specific combined assessment and management of chronic inflammation and dyslipidemia in primary prevention against T2D, particularly for young adults. The clinical benefit derived from dual-target intervention against dyslipidemia and inflammation will exceed the sum of each part alone in young adults.

Association of Traumatic Injury and Incident Myocardial Infarction and Stroke: A Prospective Population-Based Cohort Study.

Background: Several studies have linked traumatic injury and cardiovascular disease. However, few studies have investigated the associations between traumatic injury and cardiovascular disease subtypes. We aimed to prospectively examine the association between traumatic injury and the risk of incident myocardial infarction (MI) and stroke. Methods: This study was based on a prospective cohort study that included 13,973 patients who had been hospitalized for traumatic injuries from 1980 to 2020. We randomly selected 4 uninjured participants from the cohort study for each patient as controls matched by age ( ± 3 years) and sex. All participants were free of MI and stroke at enrollment. Cox regression was used to examine the association between traumatic injury and incident MI and stroke. Results: During a median follow-up period of 13.5 years, 1032 cases of MI and 4068 cases of stroke were recorded. After multivariable adjustment, relative to controls, patients with severe injury had the highest hazard ratio (HR) for MI (HR = 1.93; 95% CI: 1.26-2.96) and stroke (HR = 1.60; 95% CI: 1.25-2.05). The HRs of MI and stroke were 0.97 (0.81-1.17) and 1.11 (1.02-1.21) for patients with mild injury and 1.28 (0.97-1.69) and 1.22 (1.06 to 1.41) for patients with moderate injury. Additionally, patients with older age at injury and chest injury had a higher HR for MI and stroke (p-interaction < 0.05). Conclusions: Traumatic injury appears to be associated with an increased risk of incident MI and stroke. Therefore, early screening and prevention of MI and stroke following a traumatic injury are needed.

Serum Hs-CRP level and clinical significance of patients with stress ulcer caused by massive blood loss after trauma.

Stress ulcer refers to a specific type of irritation of the inner wall of the gastrointestinal tract that occurs rapidly due to acute physiological stress such as severe disease, infection, or trauma. This study investigated the serum Hs-CRP level and clinical significance of patients with stress ulcers caused by massive blood loss after trauma. For this purpose, we studied 113 patients with enormous blood loss after trauma. During the study, 26 patients developed stress ulcers. Therefore, patients with massive blood loss after trauma were divided into two groups with and without stress ulcers. In addition to clinical and demographical evaluations, serum Hs-CRP levels were measured by ELISA test method in all patients at baseline, 6, and 12 days after starting the study. Results showed that 24 patients were excluded from the study due to termination of cooperation or death. Finally, 89 patients participated in the final analysis. Of these 89 patients, 26 developed stress ulcers. There was a significant difference between the two groups with stress and non-stress ulcers in terms of mean age (P=0.001) and gender (P=0.041). Also, there was a significant difference between the two groups regarding re-bleeding (P=0.012), the number of hospitalization days (P=0.001), and a decrease in hemoglobin (P=0.035). But there was no difference between the two groups regarding the need for re-surgery (P=0.276). The results of this study showed that increased serum hs-CRP levels are directly related to stress ulcers. Patients with higher serum Hs-CRP levels were more likely to develop stress ulcers than patients without stress ulcers during six days (P=0.04) and twelve days after starting the study (P=0.001). Current research results also show that the prevalence of stress ulcers occurs in men more than women. The risk of stress ulcers increases among older patients. People with stress ulcers also lose more hemoglobin, and finally, patients with more trauma and more extended hospital stays have a higher chance of developing stress ulcers.

Longitudinal Study of Brachial-Ankle Pulse Wave Velocity and Change in Estimated Glomerular Filtration Rate among Chinese Adults.

BACKGROUND AND OBJECTIVES: Studies on the association between arterial stiffness and kidney function have generated inconsistent results. Whether arterial stiffness is linked to decline in renal function warrants further study. This study aimed to investigate the association between brachial-ankle pulse wave velocity (baPWV) and longitudinal change in estimated glomerular filtration rate (eGFR) among Chinese adults. METHODS: In this longitudinal study, 8,264 participants in a community-based cohort had baPWV measured in 2010-2011 and were followed in subsequent surveys through to 2016. During each survey visit, fasting blood samples were collected for serum creatinine and eGFR was calculated. Participants were divided into 5 groups (Q1-Q5) by baPWV quintile. The association between baPWV and longitudinal changes in eGFR was assessed using generalized estimating equation models. RESULTS: A total of 8,045 participants were included in the final analysis. The average age was 54 ± 12 years (age range 24-97 years), and mean eGFR was 93.0 ± 18.6 mL/min/1.73 m2. There was an inverse linear association between baseline baPWV and eGFR change rate (p < 0.001). Compared with Q1 (lowest) group, the mean differences and 95% CI in eGFR decrease rate among Q2-Q5 groups were -0.23 (-0.62, 0.16), -0.67 (-1.06, -0.28), -1.11 (-1.50, -0.72), and -1.30 (-1.69, -0.92) mL/min/1.73 m2 per year, respectively, after adjustment for age, gender, and other potential confounders (p trend < 0.0001). For each 100 cm/s increase in baPWV at baseline, the fully adjusted mean difference in eGFR decrease rate was -0.14 mL/min/1.73 m2 per year (95% CI -0.18, -0.10; p < 0.0001). Compared with participants with baPWV < 1,400 cm/s, the fully adjusted mean difference in eGFR decrease rate was -0.92 mL/min/1.73 m2 per year (95% CI -1.18, -0.66) for those with baPWV ≥ 1,400 cm/s (p < 0.0001). CONCLUSIONS: Participants with a higher baPWV at baseline had a greater decrease in eGFR over time. Future studies could examine the relationship between baPWV and decline in renal function in higher risk cohorts, and its potential role in targeting reno-protective interventions to those who may benefit from them most.

The Cumulative Exposure to High-Sensitivity C-Reactive Protein Predicts the Risk of Chronic Kidney Diseases.

BACKGROUND AND OBJECTIVES: This study was to characterize the association of cumulative exposure to increased high-sensitivity C-reactive protein (hs-CRP) with chronic kidney diseases (CKD). METHODS: We included 35,194 participants with hs-CRP measured at three examinations in 2006, 2008, 2010. Participants were classified into nonexposed group (hs-CRP <3.0 mg/L in all 3 examinations), 1-exposed group (hs-CRP ≥3.0 mg/L in 1 of the 3 examinations), 2-exposed group (hs-CRP ≥3.0 mg/L in 2 of the 3 examinations), and 3-exposed group (hs-CRP ≥3.0 mg/L in 3 examinations). Cox proportional hazards models were used to assess the association of cumulative hs-CRP with incident CKD. CKD includes an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or urinary protein positive. RESULTS: The study showed the risk of CKD as the number of years of exposure to hs-CRP increases. Participants in 3-exposed group had significantly increased CKD risk with hazard ratio (HR) (95% confidence interval, CI) of 1.70 (1.49-1.93), in comparison with 1.47 (1.34-1.62) for participants in the 2-exposed group, and 1.08 (1.00-1.16) for those in the 1-exposed group (p < 0.01); meanwhile, the similar and significant associations were also observed for eGFR <60 mL/min/1.73 m2, proteinuria positive, in participants of the 3-exposed group in comparison with the nonexposed group, with respective HRs (95% CI) of 1.27 (1.01-1.58) and 2.27 (1.87-2.76). CONCLUSIONS: Cumulative exposure to hs-CRP was associated with a subsequent increased risk of CKD and was of great value to risk prediction.

Resting Heart Rate Trajectory Pattern Predicts Arterial Stiffness in a Community-Based Chinese Cohort.

OBJECTIVE: To examine whether the long-term resting heart rate (RHR) pattern can predict the risk of having arterial stiffness in a large ongoing cohort. APPROACH AND RESULTS: This community-based cohort included 12 554 participants in the Kailun study, who were free of myocardial infarction, stroke, arrhythmia, and cancer. We used latent mixture modeling to identify RHR trajectories in 2006, 2008, and 2010. We used multivariate linear regression model to examine the association between RHR trajectory patterns and the risk of having arterial stiffness, which was assessed by brachial-ankle pulse wave velocity in 2010 to 2016. We adjusted for possible confounding factors, including socioeconomic status, lifestyle factors, use of medications, comorbidities, and serum concentrations of lipids, glucose, and high-sensitivity C-reactive proteins. We identified 5 distinct RHR trajectory patterns based on their 2006 status and on the pattern of change during 2006 to 2010 (low-stable, moderate-stable, moderate-increasing, elevated-decreasing, and elevated-stable). We found that individuals with elevated-stable RHR trajectory pattern had the highest brachial-ankle pulse wave velocity value and individuals with the low-stable RHR trajectory pattern had the lowest value (adjusted mean difference=157 cm/s; P<0.001). Adjusted odds ratio for risk of having arterial stiffness (brachial-ankle pulse wave velocity ≥1400 cm/s) was 4.14 (95% confidence interval, 2.61-6.57) relative to these 2 extreme categories. Consistently, a higher average RHR, a higher annual RHR increase rate, and a higher RHR variability were all associated with a higher risk of having arterial stiffness. CONCLUSIONS: Long-term RHR pattern is a strong predictor of having arterial stiffness.

Robust Small Target Co-Detection from Airborne Infrared Image Sequences.

In this paper, a novel infrared target co-detection model combining the self-correlation features of backgrounds and the commonality features of targets in the spatio-temporal domain is proposed to detect small targets in a sequence of infrared images with complex backgrounds. Firstly, a dense target extraction model based on nonlinear weights is proposed, which can better suppress background of images and enhance small targets than weights of singular values. Secondly, a sparse target extraction model based on entry-wise weighted robust principal component analysis is proposed. The entry-wise weight adaptively incorporates structural prior in terms of local weighted entropy, thus, it can extract real targets accurately and suppress background clutters efficiently. Finally, the commonality of targets in the spatio-temporal domain are used to construct target refinement model for false alarms suppression and target confirmation. Since real targets could appear in both of the dense and sparse reconstruction maps of a single frame, and form trajectories after tracklet association of consecutive frames, the location correlation of the dense and sparse reconstruction maps for a single frame and tracklet association of the location correlation maps for successive frames have strong ability to discriminate between small targets and background clutters. Experimental results demonstrate that the proposed small target co-detection method can not only suppress background clutters effectively, but also detect targets accurately even if with target-like interference.

Severity and Remission of Metabolic Dysfunction-Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence.

BACKGROUND: The association of the severity of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. METHODS AND RESULTS: The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m2 or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow-up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non-MAFLD (HR, 1.12 [95% CI, 1.09-1.16]), and this risk increased with increasing severity of hepatic steatosis (P-trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non-MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95-1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non-MASLD (HR, 1.15 [95% CI, 1.03-1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild-MAFLD/MASLD remission compared with persistent non-MAFLD/MASLD, but moderated/severe-MAFLD/MASLD remission still had a higher risk. CONCLUSIONS: The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.

Hypertension combined with atherosclerosis increases the risk of heart failure in patients with diabetes.

The increase in heart failure risk in the diabetic population when hypertension and atherosclerosis are both present is still inconclusive. The aim of this study was to explore the effects of hypertension combined with atherosclerosis in diabetic population on the risk of heart failure. We selected 10,711 patients with diabetes who participated in the Kailuan study and completed brachial-ankle pulse wave velocity (baPWV) testing for statistical analysis. The subjects were divided into the non-hypertensive non-atherosclerotic, hypertensive, atherosclerotic, and hypertensive atherosclerotic groups based on their history of hypertension and atherosclerosis. At a median follow-up of 4.15 years, 227 cases of heart failure occurred. Compared with the non-hypertensive non-atherosclerotic group, the multifactorial Cox proportional risk regression model showed that the hazard ratio (HR) for heart failure in the hypertensive atherosclerotic group was 3.08 (95% confidence interval [CI]: 1.32-7.16), whereas the HR decreased to 2.38 (95% CI: 1.01-5.63) after gradual correction of lipid-lowering, glucose-lowering, and antihypertensive drugs. The subgroup analysis and sensitivity analysis were consistent with that of total population. In conclusion, patients with diabetes exposed to both hypertension and atherosclerosis had an increased heart failure risk, which was attenuated by the use of lipid-lowering, glucose-lowering, and antihypertensive drugs.

Triglyceride levels and risk of cardiovascular disease and all-cause mortality in Chinese adults younger than 40 years old: a prospective cohort study.

Background: Data on the associations of triglyceride (TG) levels with cardiovascular disease (CVD) and all-cause mortality mainly focused on the middle-aged or elderly population, with limited information available for younger adults. This study aimed to identify such associations among Chinese young adults. Methods: This study included Chinese adults younger than 40 years free of CVD, cancer, and lipid-lowering agents at baseline in the Kailuan study who were enrolled during 2006 through 2016. All participants were biennially followed up till December 2020. The enzymatic colorimetric method was used to measure baseline fasting TG. Participants were categorized into four groups by quartiles of TG, with the lowest quartile (Q1) as the reference group. The primary outcomes were CVD [composite of myocardial infarction (MI) and ischemic stroke] and all-cause mortality. CVD and mortality risks were estimated with Cox regression models. Results: A total of 43,882 participants were included. Their mean age was 30.6±5.56 years, and 80.2% were males. During a median follow-up of 11.2 years, 298 CVD events and 345 deaths occurred. The incidences of CVD and all-cause mortality were 0.67 and 0.76 per 1,000 person-years, respectively. Compared with individuals in the lowest quartile (Q1), participants in the highest quartile (Q4) showed a 126% higher risk of developing CVD [adjusted hazard ratio (HR) 2.26; 95% confidence interval (CI): 1.56 to 3.29; P=0.001] and a 61% higher risk of all-cause mortality (adjusted HR 1.61; 95% CI: 1.14 to 2.28; P=0.007). In addition, analyses of CVD subtypes showed that adjusted HRs (Q4 vs. Q1) were 3.25 (95% CI: 1.33 to 7.97; P=0.01) for MI, and 1.88 (95% CI: 1.16 to 3.04; P=0.01) for ischemic stroke. Conclusions: Among Chinese young adults, elevated fasting TG levels were associated with increased CVD and all-cause mortality risks.

Life's essential 8 and cardiovascular disease among patients with hyperuricemia: The Kailuan Cohort Study.

OBJECTIVES: Studies have found that a high Life's Essential 8 (LE8) score is associated with a reduced risk of cardiovascular disease(CVD) in cancer populations and young adults. However, the association between LE8 and the risk of CVD in hyperuricemia (HUA) is not fully understood. METHODS: The main analysis included 6814 HUA participants. In a secondary analysis, 5,418 participants were selected from the main analysis to model the trajectory of uric acid (UA) levels from 2006 to 2010. Cox regression model was used to investigate the relationship between LE8 total score and cardiovascular disease risk in different populations. RESULTS: Follow-up of 15.79 years in the main analysis, 986 CVD events occurred. With tertile 1 as the control group, the HR and 95 % CI of CVD in tertile 2 and tertile 3 were 0.75(0.65,0.87) and 0.56(0.47,0.66). In the secondary analysis, the HR and 95 %CI of individuals with low and medium levels of UA reduced CVD were 0.49(0.26,0.89) and 0.56(0.41,0.76), respectively, but this association was not found in individuals with sustained high UA levels. The risk of CVD was different between the sexes. There are differences in cardiovascular disease risk among different age groups. CONCLUSIONS: The risk of CVD in HUA population decreased with the increase of LE8 score, especially in young and middle-aged people and women. However, it is important to note that LE8 may not reduce the risk of CVD in individuals with sustained high UA levels.

Perceived Taste and Olfactory Dysfunctions and Subsequent Stroke Risk.

Background: Taste and olfactory dysfunction are commonly associated with neurodegenerative diseases and cardiovascular risk factors, but their specific associations with stroke risk remain uncertain. Objectives: The purpose of this paper was to explore whether perceived taste and olfactory dysfunctions were associated with stroke risk. Methods: Included were 85,656 participants (mean age 51.0 ± 15.3 years) of the Kailuan study. Perceived olfactory and taste dysfunctions were assessed via a questionnaire at baseline (in 2014-2016). Incident stroke cases were confirmed by review of medical records. Cox proportional hazards models were used to investigate associations of perceived olfactory and taste dysfunctions with stroke risk, and mediation analysis was used to estimate the mediating effect of chronic disease statuses. Results: We documented 2,198 incident stroke cases during a mean of 5.6 years of follow-up. Perceived taste dysfunction was associated with a doubled risk of developing total stroke (adjusted HR: 2.03; 95% CI: 1.36-3.04; P < 0.001) even with adjustment of lifestyle factors, biomarkers (ie, blood lipids, blood glucose, blood pressure, and uric acid), and other potential confounders. However, perceived olfactory dysfunction (adjusted HR: 1.22; 95% CI: 0.79-1.90; P = 0.34) was not significantly associated with a high risk of total stroke. Similar results of both perceived taste and olfactory dysfunctions were observed for ischemic stroke. Presence of chronic diseases, including hypertension, diabetes, chronic kidney disease, and overweight/obesity, mediated 4% to 5% of the association of perceived taste dysfunction with both total stroke and ischemic stroke. Conclusions: In this large cohort study, perceived taste dysfunction was associated with a high risk of developing stroke.

Female Protection Against Diabetic Kidney Disease Is Regulated by Kidney-Specific AMPK Activity.

Reduced kidney AMPK activity is associated with nutrient stress-induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress-induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes was evaluated in diabetic kidney tubule-specific AMPKγ2KO (KTAMPKγ2ΚΟ) male and female mice. In wild-type (WT) males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKγ2ΚΟ. Whereas WT females had protection against diabetes-induced kidney injury, KTAMPKγ2ΚΟ led to loss of female protection against kidney disease. The hormone 17ß-estradiol ameliorated high glucose-induced AMPK inactivation, p70S6K phosphorylation, and matrix protein accumulation in kidney tubule cells. The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA sequencing and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges.

LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

[Impact of systolic blood pressure on visit-to-visit blood pressure variability in middle-aged and elderly people].

OBJECTIVE: To observe the impact of systolic blood pressure (SBP) on visit-to-visit blood pressure variability (BPV) in middle-aged and elderly people. METHODS: Visit-to-visit BPV was determined in 5440 workers in the Kailuan study cohort from 2006 to 2007. The subjects were ≥ 40 years-old and had no history of stroke, transient ischemic attack or myocardial infarction. Participants were divided into five groups according to different levels of SBP. Linear regression was used to analyze the related factors which might affect BPV. RESULTS: Mean systolic BPV of all subjects was 10.35 mm Hg [coefficient of variation (CV 7.96%)]. The mean systolic BPV of males was 10.54 mm Hg (CV 7.90%) while the mean SBPV of females was 10.06 mm Hg (CV 7.90%). The BPV of males was significant higher than that of females (P < 0.001). CV of SBP was similar between males and females. Furthermore, higher SBP was associated with higher BPV. There were significant differences in BPV between different groups with different levels of SBP (P < 0.001). Linear regression analysis demonstrated that SBP, age, gender, high-sensitivity C-reactive protein (hsCRP) were affecting factors of BPV. Twenty mm Hg SBP increase was linked with 2.02 mm Hg BPV increase and 0.388%CV increase. Age increase of 1 year was associated with 0.044 mm Hg BPV increase and 0.029% CV increase. CONCLUSION: SBP, age, gender and hsCRP are important factors affecting BPV in middle-aged and elderly people. Higher SBP is closely related to greater BPV in this cohort.

The Relationship between Vascular Aging Phenotypes and Renal Damage among Individuals with Type 2 Diabetes.

OBJECTIVE: The aim of this study was to investigate the relationship between vascular aging (VA) phenotypes and renal damage in type 2 diabetic population. METHODS: In this cross-sectional study, we included 8,141 individuals with type 2 diabetes who participated in the Kailuan Study during 2010-2018 and completed the brachial-ankle pulse wave velocity (baPWV) assessment for arterial stiffness, an indicator for VA. The age- and sex-specific 10th and 90th percentiles of baPWV based on a reference cohort were used as cutoffs to define supernormal VA (SUPERNOVA, baPWV<10th percentiles), normal VA (NVA, baPWV 10th to 90th percentiles), and early VA (EVA, baPWV>90th percentiles). The estimated glomerular filtration rate (eGFR) and proteinuria levels were used to assess renal damage, including isolated proteinuria, isolated kidney function decline (eGFR<60 mL/min/1.73 m2), and proteinuria combined with kidney function decline. Multivariable logistic regression analysis was used to analyze the relationship between VA phenotypes and diabetic kidney damage. RESULTS: The prevalences of isolated proteinuria, isolated kidney function decline, and proteinuria combined with kidney function decline were 17.0%, 12.2%, and 5.4%, respectively. Compared with NVA, SUPERNOVA was associated with 34% lower odds (95% confidence interval [CI]: 0.46-0.96) of isolated proteinuria after adjusting for age, sex, and other potential confounders. EVA was associated with higher odds of all three types of kidney damage; the adjusted odds ratio (95% CI) was 1.42 (1.20-1.67) for proteinuria, 1.24 (1.01-1.51) for kidney function decline, and 1.56 (1.18-2.06) for proteinuria combined with kidney function decline. CONCLUSIONS: VA phenotypes are associated with renal damage, especially isolated proteinuria. SUPERNOVA was associated with lower odds of isolated proteinuria and EVA was associated with higher odds of proteinuria and kidney function decline.

Better Life's Essential 8 Is Associated With Lower Risk of Diabetic Kidney Disease: A Community-Based Study.

Background Diabetic kidney disease (DKD) is a common diabetic complication and increases the complexity of diabetes management. No prospective study has focused on the association between DKD and Life's Essential 8 (LE8). Our study aims to examine the association between LE8 and DKD risk. Methods and Results A total of 7605 participants, aged 54.32±9.77 years, and 4688 participants, aged 56.11±10.38 years, were included in the longitudinal and trajectory analyses, respectively, from 2006 to 2020. The DKD was confirmed using data collected during each follow-up. LE8 was based on 4 health behaviors and 4 health factors. The range of each metric was 0 to 100, and the overall LE8 score was calculated as the unweighted average of all 8 component metric scores. The trajectories of LE8 during 2006 to 2010 were classified using latent mixture models. Cox models and restricted cubic splines were applied. After a median follow-up of 12.41 and 6.71 years in longitudinal and trajectory analyses, respectively, the DKD incidence decreased, with the LE8 level increasing (P-trend<0.05), and the linearity assumption for this relationship (P-nonlinear=0.685) had been satisfied. Adjusted hazard ratios (HRs) for the highest tertile were 0.77 (95% CI, 0.69-0.87) and 0.70 (95% CI, 0.62-0.78) in baseline and time-updated LE8 scores, respectively, compared with the lowest tertile. Adjusted HR was 0.53 (95% CI, 0.41-0.69) for the stable-high pattern compared with the stable-low pattern. Conclusions Although LE8 is an indicator of cardiovascular health, the beneficial impact of a high LE8 score is also evident in the protection of renal health among patients with diabetes.

Cost-effectiveness of drug treatment for young and middle-aged stage 1 hypertensive patients with high risk.

Background: Drug treatment was recommended for stage 1 hypertensive patients (blood pressure of 130-139 / 80-89 millimetres of mercury (mmHg)) with high cardiovascular disease (CVD) risk in the 2017 Hypertension Clinical Practice Guidelines, 2018 Chinese guidelines and 2021 World Health Organization guidelines, but not in other guidelines. However, evidence on the cost-effectiveness of drug treatment among young and middle-aged patients remains scarce. This study aimed to compare the cost-effectiveness of drug treatment vs. non-drug treatment for stage 1 hypertensive patients aged <60 years with high CVD risk. Methods: A microsimulation model projected quality-adjusted life years (QALYs), health care costs, and incremental cost-effectiveness ratios for drug treatment from a societal perspective. Transition probabilities were estimated from the Kailuan study with a sample size of 34 093 patients aged <60 years with high CVD risk. Costs and health utilities were obtained from the Kailuan study, national statistics reports and published literature. Results: Over a 15-year time horizon, the model predicted that drug treatment generated QALY of 9.36 and was associated with expected costs of 3735 US dollars ($) compared with 9.07 and $3923 produced by non-drug treatment among stage 1 hypertensive patients, resulting in a cost-saving for drug treatment. At a willingness-to-pay threshold of $10439/QALY (one gross domestic product (GDP) per capita in 2020), drug treatment had a 99.99% probability of being cost-effective for 10 000 samples of probabilistic sensitivity analysis. Sensitivity analyses by different values of transition probability, cost, utility and discount rate did not appreciably change the results. Shortening the time horizon to the average follow-up period of eight years resulted in ICER of $189/QALY for drug treatment (<1 × GDP/QALY). Conclusions: Our results suggested that drug treatment was a dominant strategy for stage 1 hypertensive patients aged <60 years with high CVD risk in China, which may provide evidence for policymakers and clinicians when weighing the pros and cons of drug treatment for young and middle-aged stage 1 hypertensive patients.