Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study.

BACKGROUND AND AIMS: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden. METHODS: This study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk. RESULTS: A total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59-3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21-2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002-1.006, P < 0.001) . CONCLUSION: Elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. WHAT IS ALREADY KNOWN ON THIS TOPIC?: Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear. WHAT THIS STUDY ADDS?: Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY?: Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

Association of blood cadmium with all-cause and cause-specific mortality in patients with hypertension.

Background: Cadmium is a commonly found heavy metal with a prolonged biological half-life, which results in long-term health burden for the population. Prior studies have demonstrated an association between blood cadmium and hypertension. However, few studies examined the relationship between blood cadmium and long-term health outcomes in patients with hypertension. This study aimed to investigate the association of blood cadmium with mortality in patients with hypertension. Methods: This study analyzed data from the National Health and Nutrition Examination Survey 1999-2012. Complex sampling-weighted multivariate Cox proportional hazards models were used to evaluate the hazard ratios (HRs) of all-cause, cardiovascular, and Alzheimer's disease mortality in patients with hypertension classified by blood cadmium concentrations' quantiles. Results: The study included 12,208 patients with hypertension with a median follow-up duration of 10.8 years. During this period, there were 4,485 all-cause deaths, including 1,520 cardiovascular deaths and 180 Alzheimer's disease deaths. Compared with the lowest quintile of blood cadmium (≤0.25 µg/L) group, the highest quintile of blood cadmium (≥0.80 µg/L) group's adjusted HRs were 1.85 (95% CI, 1.59-2.14) for all-cause mortality, 1.76 (95% CI, 1.33-2.34) for cardiovascular mortality, and 3.41 (95% CI, 1.54-7.51) for Alzheimer's disease mortality. Additionally, the adjusted HR for cardiovascular mortality was 2.12 (95% CI, 1.36-3.30) in never-smoking patients with hypertension. Conclusion: Higher blood cadmium is associated with increased risks of all-cause, cardiovascular, and Alzheimer's disease mortality in patients with hypertension. The effect of blood cadmium on cardiovascular mortality may be more pronounced in never-smoking hypertensive patients.

Clinical characteristics and outcome correlates of Chinese patients with takotsubo syndrome: Results from the first Chinese takotsubo syndrome registry.

OBJECTIVE: To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS). METHODS: We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients. RESULTS: In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049). CONCLUSION: We investigated clinical and outcome features of patients in the first Chinese TTS Registry. Tachycardiac TTS patients developed more inpatient and long-term adverse cardiovascular events.

Epidemiological study of calcified aortic valve stenosis in a Chinese community population.

BACKGROUND AND AIMS: Due to the ageing global population, calcified aortic valve disease is currently the most common cardiac valve disorder. This study aimed to investigate the prevalence and the risk factors for calcified aortic valve stenosis (CAVS), and develop a prediction model for predicting CAVS risk. METHODS AND RESULTS: This study was derived from the cross-sectional baseline survey of the PRECISE study (NCT03178448). The demographic, clinical and laboratory information of each participant was obtained. Univariable and multivariable logistic regression models were used to determine CAVS risk factors. A prediction model for predicting CAVS risk based on risk factors was developed and the result was performed by nomogram. The discrimination of the prediction model was assessed by receiver operating characteristic curve analysis. The degree of fitting for the prediction model was assessed by calibration curve analysis. A total of 3067 participants (1427 men and 1640 women) were included. The prevalence of CAVS among those aged below 60 years old, 60-70 years old and over 70 years old was 4.1%, 10.3% and 21.9%, respectively. Multivariable regression analysis revealed that age (OR: 1.099; 95% CI: 1.076 to 1.123, p<0.001), pulse pressure (OR: 1.020; 95% CI: 1.009 to 1.031, p<0.001), uric acid (OR: 1.003; 95% CI: 1.001 to 1.004, p<0.001), glycosylated haemoglobin (HbA1c) (OR: 1.152; 95% CI: 1.028 to 1.292, p=0.015) and lipoprotein(a) (OR: 1.002; 95% CI: 1.001 to 1.002, p<0.001) were independent risk factors for CAVS. High-density lipoprotein cholesterol (HDL-C) was a protective factor for CAVS (OR: 0.539; 95% CI: 0.349 to 0.831, p=0.005). The prediction model including the above risk factors showed a risk prediction of CAVS with good discrimination. The area under the curve value was found to be 0.743 (95% CI: 0.711 to 0.775). CONCLUSION: CAVS is currently prevalent in the elderly Chinese population. Age, pulse pressure, HbA1c, lower-level HDL-C, lipoprotein(a) and uric acid are the independent risk factors for CAVS.

Prevalence and Vascular Distribution of Multiterritorial Atherosclerosis Among Community-Dwelling Adults in Southeast China.

Importance: Data are limited on the prevalence and vascular distribution of multiterritorial atherosclerotic plaque and stenosis in community populations. Objective: To investigate the prevalence and vascular distribution of multiterritorial atherosclerotic plaque and stenosis in older, community-dwelling populations in China. Design, Setting, and Participants: This cross-sectional study was based on the baseline survey from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study, a population-based prospective cohort study that enrolled community-dwelling adults aged 50 to 75 years based on cluster sampling from 6 villages and 4 living communities of Lishui city in southeast China. Data were collected from May 2017 to September 2019 and analyzed from September to November 2021. Main Outcomes and Measures: Atherosclerotic plaque and stenosis at baseline were assessed in multiple vascular territories. Brain vessel wall magnetic resonance imaging (MRI) for intracranial and extracranial arteries; computed tomography angiography (CTA) for coronary, subclavian, aorta, renal, and iliofemoral arteries; and ankle-brachial index for peripheral arteries were performed at baseline survey. The extent of atherosclerosis was assessed according to the number of these 8 vascular sites affected, and polyvascular lesions were defined as at least 2 affected sites. Results: A total of 3433 of 4202 invited individuals consented to participate in the study. After excluding 366 participants with contraindications for MRI or CTA scanning, with life expectancies of 4 years of fewer, or with mental disease, a total of 3067 community-dwelling adults were enrolled. The mean (SD) age was 61.2 (6.7) years; 1640 (53.5%) were women, and 74 (2.4%) had prevalent ASCVD. Most participants (2870 [93.6%]) had atherosclerotic plaques in at least 1 vascular territory. Atherosclerotic plaques were mostly detected in the aorta (2419 [79.6%]) and iliofemoral arteries (2312 [75.8%]), followed by subclavian (1500 [49.8%]), coronary (1366 [44.9%]), extracranial (1110 [36.4%]), renal (873 [28.7%]), and intracranial (542 [17.7%]) arteries. A substantial proportion of participants (1180 [38.5%]) had arterial stenosis of 50% or greater, predominantly affecting the coronary (542 [17.8%]) and iliofemoral (527 [17.3%]) arteries. Polyvascular atherosclerotic plaque was observed in 2541 participants (82.8%), with 1436 (46.8%) with plaque affecting 4 or more vascular territories, and polyvascular stenosis was observed in 412 patients (13.4%). Conclusions and Relevance: In this study, atherosclerotic plaque was highly prevalent in the older community population in China, and a substantial proportion of individuals reach stenosis of 50% or greater.

Association of caffeine intake with all-cause and cardiovascular mortality in elderly patients with hypertension.

Background: Caffeine is widely consumed not only in coffee but also in soft drinks and tea. However, the long-term health effects of caffeine are still controversial, especially in people with high cardiovascular risk such as elderly patients with hypertension. Methods: This study analyzed data from the National Health and Nutrition Examination Survey 2003-2018. Caffeine intake was calculated by two 24-h dietary recall interviews. Complex sampling-weighted multivariable Cox proportional hazards models were used to compare the hazard ratios (HRs) of all-cause and cardiovascular mortality in elderly hypertensive patients with different caffeine intake (<10, 10 to <100, 100 to <200, 200 to <300, and ≥300 mg/day). Results: This study included 6,076 elderly hypertensive patients. The mean ± standard error follow-up duration was 6.86 ± 0.12 years. During this period, a total of 2,200 all-cause deaths occurred, of which 765 were cardiovascular deaths. Taking patients with caffeine intake < 10 mg/day as a reference, patients with moderate caffeine intake (200 to <300 mg/day) had a lower risk of all-cause (HR, 0.70 [95% CI, 0.56-0.87]) and cardiovascular (HR, 0.55 [95% CI, 0.39-0.77]) mortality. The benefit of reducing all-cause mortality risk was significant in female patients (HR, 0.65 [95% CI, 0.50-0.85]) or patients with well-controlled blood pressure (HR, 0.63 [95% CI, 0.46-0.87]), but not in male patients or patients with poorly controlled blood pressure. In addition, non-linear relationship analysis also showed that moderate caffeine intake had the lowest HRs of all-cause (Non-linear p = 0.022) and cardiovascular mortality (Non-linear p = 0.032) in the present study. Conclusion: Moderate caffeine intake is associated with reduced risk of all-cause and cardiovascular mortality in elderly hypertensive patients.

Estimated plasma volume status (ePVS) is a predictor for acute myocardial infarction in-hospital mortality: analysis based on MIMIC-III database.

BACKGROUND: Estimated plasma volume status (ePVS) has been reported that associated with poor prognosis in heart failure patients. However, no researchinvestigated the association of ePVS and prognosis in patients with acute myocardial infarction (AMI). Therefore, we aimed to determine the association between ePVS and in-hospital mortality in AMI patients. METHODS AND RESULTS: We extracted AMI patients data from MIMIC-III database. A generalized additive model and logistic regression model were used to demonstrate the association between ePVS levels and in-hospital mortality in AMI patients. Kaplan-Meier survival analysis was used to pooled the in-hospital mortality between the various group. ROC curve analysis were used to assessed the discrimination of ePVS for predicting in-hospital mortality. 1534 eligible subjects (1004 males and 530 females) with an average age of 67.36 ± 0.36 years old were included in our study finally. 136 patients (73 males and 63 females) died in hospital, with the prevalence of in-hospital mortality was 8.9%. The result of the Kaplan-Meier analysis showed that the high-ePVS group (ePVS ≥ 5.28 mL/g) had significant lower survival possibility in-hospital admission compared with the low-ePVS group (ePVS < 5.28 mL/g). In the unadjusted model, high-level of ePVS was associated with higher OR (1.09; 95% CI 1.06-1.12; P < 0.001) compared with low-level of ePVS. After adjusted the vital signs data, laboratory data, and treatment, high-level of ePVS were also associated with increased OR of in-hospital mortality, 1.06 (95% CI 1.03-1.09; P < 0.001), 1.05 (95% CI 1.01-1.08; P = 0.009), 1.04 (95% CI 1.01-1.07; P = 0.023), respectively. The ROC curve indicated that ePVS has acceptable discrimination for predicting in-hospital mortality. The AUC value was found to be 0.667 (95% CI 0.653-0.681). CONCLUSION: Higher ePVS values, calculated simply from Duarte's formula (based on hemoglobin/hematocrit) was associated with poor prognosis in AMI patients. EPVS is a predictor for predicting in-hospital mortality of AMI, and could help refine risk stratification.

The association of fracture risk in atrial fibrillation patients and long-term anticoagulant therapy category: a systematic review and meta-analysis.

OBJECTIVE: Our study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin. METHODS: We searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893). RESULTS: We included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81-1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82-1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80-0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76-0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin. CONCLUSION: The meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.

Correlation between Renal Artery Anatomy and Hypertension: A Retrospective Analysis of 3000 Patients.

OBJECTIVE: To assess the correlation between renal artery anatomy and blood pressure in Undiagnosed Hypertension and Diagnosed Hypertension. METHODS: The renal artery CT scanning imaging data and laboratory data of 3000 inpatients and outpatients were collected retrospectively in 4 centers of China. Morphometric parameters were assessed using the quantitative vascular analysis (unit: mM). RESULTS: 687 cases (23.2%) had accessory renal arteries unilaterally, and 216 cases (7.3%) had bilateral accessory renal arteries, including left kidney 825 (27.9%) and right kidney 798 (27.0%). The presence of accessory renal arteries and renal artery branches was higher in the diagnosed hypertension group as compared with the undiagnosed hypertension group (MARB, pp < 0.001; ARA, p < 0.001; others, p < 0.001). Consequently, multivariate regression analysis showed that age (OR = 2.519 (95% CI: 0.990-6.411, p < 0.001)), dyslipidemia (OR = 1.187 (95% CI: 0.960-1.454, p = 0.007)), renal hilum Outside the main renal artery branch (MRAB) (OR = 2.069 (95% CI: 1.614-2.524, p = 0.002)), and accessory renal artery (ARA) (OR = 2.071 (95% CI: 1.614-2.634, p = 0.001)) were risk factors of hypertension. In addition, higher renin activity was associated with ARA patients (2.19 ± 2.91 vs. 1.75 ± 2.85, p < 0.001). CONCLUSIONS: When comparing renal arteries side by side, the anatomical length of the renal arteries is significantly different. In addition, the prevalence of accessory renal arteries and renal artery branches is higher in the hypertension group. The auxiliary renal artery and the main renal artery branch outside the renal portal are independent factors of hypertension. Renal sympathetic nerve activity is affected by renin activity and is related to the accessory renal artery.

PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE)-a population-based prospective cohort study: rationale, design and baseline participant characteristics.

BACKGROUND AND PURPOSE: Cardiovascular diseases and dementia are two major diseases in the elderly. Atherosclerosis is associated with future vascular events and cognitive impairment. The PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study is a population-based prospective cohort study with comprehensive evaluation of multiterritorial artery stenosis and plaque using advanced vascular imaging techniques and prospective collection of vascular events and cognitive assessments. METHODS: Between May 2017 and September 2019, the PRECISE study enrolled 3067 community-dwelling adults with ages between 50 and 75 years cluster sampled from six villages and four communities of Lishui city in China. Data are collected in face-to-face interviews at baseline, 2-year and 4-year follow-up visits. Brain MRI including high-resolution sequences for intracranial and carotidal arteries and CT angiography for thoracoabdominal arteries were performed at baseline and will be rescanned after 4 years. Cardiovascular/cerebrovascular events and cognitive assessment will be prospectively collected after the enrollment. Blood and urine samples were collected and biomarkers were tested at baseline. RESULTS: A total of 3067 subjects were enrolled, among which 53.5% were female with an average age of 61.2±6.7 years. Among them, 2.8%, 8.1%, 43.1% and 21.6% had a history of stroke, coronary heart diseases, hypertension and diabetes mellitus, respectively. CONCLUSIONS: The PRECISE study is a population-based prospective cohort study with comprehensive evaluation of atherosclerotic stenosis and plaque using advanced vascular imaging techniques. Data from this cohort provide us an opportunity to precisely evaluate polyvascular atherosclerosis and its association with future vascular events and cognitive impairment. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03178448).

Cerebral microbleeds are associated with blood pressure levels in individuals with hypertension.

Objective: Cerebral microbleeds (CMBs), which appear as small dot-like hypointense lesions, are strongly associated with cerebrovascular disease. Recently, numerous investigations have suggested that hypertension and age are risk factors for CMBs; however, whether blood pressure grade and age rank are related to the severity of CMBs remains unclear. The purpose of this research was to assess the association between cerebral microbleeds and blood pressure levels.Methods: In total, 460 consecutive hypertension patients (214 males and 246 females; aged 44-96 years, mean age 60.95 ± 6.82 years) from Lishui Central Hospital were enrolled and classified as CMB or non-CMB patients according to magnetic resonance imaging (MRI). Gradient echo T2*-weighted MRI was used to detect CMBs. Differences in blood pressure, CMB severity, and other patient characteristics were compared between the two groups. Multifactorial logistic regression was used to analyze the correlation between blood pressure and microbleeds.Results: In our study, CMB lesions were identified in 123 patients (26.7%), including 39 patients with CMB lesions located deep in the brain. In the hypertensive population, smoking is an independent risk factor for CMBs. Additionally, systolic blood pressure (SBP), diastolic blood pressure (DBP) and age are also independent risk factors for CMBs. Furthermore, a modest correlation was noted between the number of microbleeds and grade of hypertension.Conclusions: This study provides novel evidence that microbleed severity is associated with hypertension grade. This conclusion emphasizes the importance of antihypertensive therapy in hypertension patients to avoid an increase in CMBs.

Mechanical interventricular dependency supports hemodynamics in tako-tsubo cardiomyopathy.

BACKGROUND: Although morphological abnormalities of the heart appear to be remarkable, most patients with tako-tsubo cardiomyopathy (TTC) remain clinically stable. We investigate real time changes in the left ventricular (LV) and right ventricular (RV) mechanics and function to explore the mechanism to preserve hemodynamics. METHODS: With deformation and Doppler echocardiography, we evaluated myocardial mechanics and ventricular function/hemodynamics simultaneously in 103 consecutive TTC patients admitted from 01/01/2008 through 12/31/2015. The coronary angiography and left ventriculography were performed to rule out culprit coronary artery stenosis (CAS). We included 66 patients in a control group with matched age, sex, and risk factors for coronary artery disease (CAD), and 41 patients in a group of myocardial infarction induced cardiogenic shock, who required circulatory supporting devices to maintain hemodynamic stability. RESULTS: Although systolic myocardial strain in most of the LV segments was significantly impaired, 4 basal LV segments remained functionally active during acute stage of TTC. The impairment in the myocardial strain of the RV apex could extend to the middle segments, but basal RV systolic strain was also preserved. Despites comparable apical to basal strain gradients, LV and RV displayed discrepant functional/hemodynamic status. In contrast to LV, RV functional/hemodynamic parameters appeared to be hyper-dynamic. This unique RV strain pattern remained unchanged in patients with atypical (mid-LV cavity) TTC. In 41 patients with myocardial infarction induced cardiogenic shock, RV exhibited comparable mechanic and functional features with those in TTC patients. CONCLUSIONS: The identified LV and RV mechanic changes appear to support interventricular hemodynamic dependence during TTC, which may represent a universal rescue mechanism in a jeopardized or injured heart.