Heavy metal exposure linked to metabolic syndrome in Korean male firefighters: FRESH cohort cross-sectional analysis.

This study aimed to identify the relationship between blood lead and Cadmium (Cd) concentrations and metabolic syndromes (MetS), including its components (central obesity, hypertriglyceridemia, low high-density lioioritein, hypertension, and hyperglycemia) among Korean firefighters. A total of 965 firefighters of the Enhancement of Safety and Health cohort were analyzed in this study. MetS was defined according to the 2005 revised National Cholesterol Education Program-Adult Treatment Panel III criteria and the Korean Society for the Study of Obesity criteria for waist circumference. The collected data were analyzed using a logistic regression model. Of the 965 participants, 190 (19.7%) had MetS. After adjusting for age, body mass index, smoking, drinking, exercise, shift duty, and main duty position, the Cd level was significantly associated with an increased risk of MetS in the Korean firefighter population (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.07, 2.46). This association was significant among non-smokers and ex-smokers (OR = 1.58, 95% CI 1.03, 2.43), non-drinkers and ex-drinkers (OR = 1.77, 95% CI 1.06, 2.94), firefighters aged 40 year or older (OR = 1.77, 95% CI 1.10, 2.86), and office administrators (OR = 3.85, 95% CI 1.42, 10.39). This outcome suggests that exposure to Cd is likely to increase risk of MetS among firefighters.

Clinical and life style factors related to the nighttime blood pressure, nighttime dipping and their phenotypes in Korean hypertensive patients.

BACKGROUND: Non-dipping or reverse dipping patterns are known to be associated with adverse cardiovascular prognosis among the general population and clinical cohort. Few large sized studies have explored factors including sleep duration and sleep quality related to nighttime blood pressure (BP) and nocturnal dipping patterns. METHODS: Among 5,360 patients enrolled  in Korean multicenter nationwide prospective Registry of ambulatory BP monitoring (KORABP), 981 subjects with complete data on sleep duration, sleep quality assessed using a 4-point Likert scale, and clinical variables were included in the analysis. Phenotypes of nighttime BP pattern were categorized as extreme dipper, dipper, non-dipper, and reverse dipper. Hypertension was defined as a 24-h ambulatory BPs were 130/80 mmHg or higher. RESULTS: Among 981 subjects, 221 were normotensive, 359 were untreated hypertensive, and 401 were treated hypertensive. Age of the participants were 53.87 ± 14.02 years and 47.1% were female. In overall patients, sleep duration was 431.99 ± 107.61 min, and one to four points of sleep quality were observed in 15.5%, 30.0%, 30.4%, and 24.2%, respectively. Of the 760 hypertensive patients, extreme dipper, dipper, non-dipper, and reverse dipper were observed in 58 (7.63%), 277 (36.45%), 325 (42.76%), and 100 (13.16%), respectively. In multiple linear regression analysis, sleep duration (ß = 0.0105, p < 0.001) and sleep quality (ß = -0.8093, p < 0.001) were associated with nighttime systolic BP and sleep quality was associated with extent of nighttime systolic BP dipping (ß = 0.7622, p < 0.001) in hypertensive patients. In addition, sleep quality showed positive association with dipper pattern (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.03-1.30) and showed negative association with reverse dipper pattern (OR = 0.73, 95% CI = 0.62-0.86) in multiple logistic regression analyses. CONCLUSION: When adjusted covariates, less sleep duration and poor sleep quality were positively associated with nighttime systolic BP. Additionally, sleep quality was the independent associated factor for dipper and reverse dipper phenotypes. The study also found that male sex, low estimated glomerular filtration rate, high ambulatory BP, low office BP, and poor sleep quality were associated with blunted nighttime SBP dipping.

Statins and Clinical Outcomes in Patients With Low to Moderate Risk but With Non-obstructive Carotid Plaques: The SCOPE-CP Study.

BACKGROUND AND OBJECTIVES: Some individuals exhibit discrepancies between risk classifications assessed using clinical factors and those obtained by vascular imaging. We aimed to evaluate whether statins provide clinical outcome benefits in patients classified as having low to moderate cardiovascular risk but with carotid plaque. METHODS: This was a retrospective propensity score matching study. A total of 12,158 consecutive patients undergoing carotid ultrasound between January 2012 to February 2020 were screened. Individuals with low to moderate cardiovascular risk who were not currently recommended for statin therapy but had carotid plaques were included. Among 1,611 enrolled individuals, 806 (statin group: 403, control group: 403) were analyzed. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs: cardiovascular death, myocardial infarction, coronary revascularization, and ischemic stroke or transient ischemic attack) and all-cause mortality. RESULTS: During the median follow-up of 6.0 years, the incidence of MACCEs did not differ between the groups (6.1 and 5.7/1,000 person-years in the control and statin groups, respectively; adjusted hazard ratio [HR], 0.95; p=0.90). The incidence of all-cause mortality did not differ (3.9 and 3.9/1,000 person-years, respectively; adjusted HR, 1.02; p=0.97). Kaplan-Meier curves revealed similar rates of MACCEs (log-rank p=0.72) and all-cause mortality (log-rank p=0.99) in the 2 groups. Age and smoking were independent predictors of MACCEs. Subgroups exhibited no differences in clinical outcomes with statin use. CONCLUSIONS: Benefit of statin therapy was likely to be limited in low to moderate risk patients with carotid plaques. These results could guide physicians in clinical decision-making regarding cardiovascular prevention.

Hypertensive emergencies in Asia: A brief review.

Hypertensive emergency is one of the most challenging conditions to treat in the emergency department (ED). From previous studies, about 1%-3% of hypertensive individuals experienced hypertensive emergencies. Its prevalence varied by country and region throughout Asia. Asian populations have more different biological and cultural backgrounds than Caucasians and even within Asian countries. However, there is a scarcity of research on clinical features, treatment, and outcomes in multinational Asian populations. The authors aimed to review the current evidence about epidemiology, clinical characteristics and outcomes, and practice guidelines in Asia. Five observational studies and nine clinical practice guidelines across Asia were reviewed. The prevalence of hypertensive emergencies ranged from .1% to 1.5%. Stroke was the most common target organ involvement in Asians who presented with hypertensive emergencies. Although most hypertensive emergency patients required hospitalization, the mortality rate was low. Given the current lack of data among Asian countries, a multinational data repository and Asian guidelines on hypertensive emergency management are mandatory.

Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea.

Approximately 29% of Korean adults have hypertension; however, the prevalence of primary aldosteronism among the hypertensive population is largely unknown. The aim of our study was to evaluate the prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea. We retrospectively analyzed 1173 patients with newly diagnosed or preexisting hypertension who were referred to our tertiary-care hospital between January 2013 and December 2018. Patients were screened for primary aldosteronism with the aldosterone-renin ratio and underwent a saline infusion test for diagnostic confirmation. Adrenal computed tomography and adrenal venous sampling were performed for subtype classification for primary aldosteronism. Among the 1173 patients (mean age, 51.8 years; women, 53.2%), 360 (30.7%) had positive screening-test results, of whom 71 (6.1%) were finally diagnosed with primary aldosteronism. Conclusive subtype differentiation was made in 55 patients, of whom 15 (27%) had an aldosterone-producing adenoma, 4 (7%) had unilateral adrenal hyperplasia, and 36 (66%) had bilateral adrenal hyperplasia. Patients with primary aldosteronism had a higher ambulatory blood pressure, left ventricular mass index, and urinary albumin-to-creatinine ratio than those without. Moreover, the primary aldosteronism group had a higher prevalence of left ventricular hypertrophy and albuminuria than the non-primary aldosteronism group. Primary aldosteronism may be more common (6.1%) among Korean patients with hypertension than generally recognized. Primary aldosteronism was associated with a higher degree and prevalence of target organ damage and a higher blood pressure level. Wide application of screening tests for primary aldosteronism may be beneficial in detecting this potentially curable cause of hypertension.

Retinal photograph-based deep learning predicts biological age, and stratifies morbidity and mortality risk.

BACKGROUND: ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). OBJECTIVE: we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. METHODS: we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years ('RetiAGE') and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). RESULTS: in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42-1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69-3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31-1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14-1.69]) and 18% (HR = 1.18 [1.10-1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). CONCLUSIONS: the DL-derived RetiAGE provides a novel, alternative approach to measure ageing.

Soluble RAGE attenuates Ang II-induced arterial calcification via inhibiting AT1R-HMGB1-RAGE axis.

BACKGROUND AND AIMS: Arterial calcification (AC), which is an important process in the pathogenesis of atherosclerosis, is accelerated by angiotensin II (Ang II), a critical effector of the renin-angiotensin system (RAS). Receptor for advanced glycation end-product (RAGE) is an important pattern recognition receptor downstream of Ang II. Although recent studies have suggested an association between RAGE-mediated signaling and RAS in AC, the detailed mechanism, particularly in relation to Ang II, remains unclear. METHODS: Therefore, we investigated the role of RAGE-mediated signaling pathways and the therapeutic efficacy of soluble RAGE (sRAGE) in Ang II-induced AC, using both a human aortic smooth muscle cell (HAoSMC) model, and an in vivo apolipoprotein E knockout (ApoE KO) mouse model. RESULTS: According to our data, Ang II significantly increased the calcification of HAoSMCs, and the associated activation of RAGE was mediated by subsequent HMGB1 release through Angiotensin II type 1 receptor activation. Both HMGB1 neutralizing antibody and sRAGE inhibited Ang II-induced calcium deposition. Furthermore, sRAGE attenuated HMGB1 secretion and the activation of RAGE-mediated signaling. The in vivo study indicated that Ang II significantly induced calcium deposition in the aorta, and this was significantly attenuated by sRAGE. CONCLUSIONS: Our findings strongly suggest that blockade of RAGE, using sRAGE, effectively attenuates Ang II-induced arterial calcification.

Statin Therapy in HIGH-Risk Individuals with NORMal Coronary Arteries: The HIGH-NORM Study.

AIMS: Mismatches between the risk status of a patient and coronary imaging data can lead to conflicting strategies to prevent a cardiovascular event. We evaluated whether statin use was associated with cardiovascular benefit in high-risk individuals whose coronary computed tomography angiography (CCTA) results showed normal coronary arteries. METHODS: Among asymptomatic individuals whose CCTA showed normal or near normal coronary arteries, 3,389 persons with high- or very-high-risk status were included in this retrospective study. After 1:2 propensity score matching, 906 individuals (302 new statin users and 604 controls; mean age 61 years; male 58%) were analysed. The primary outcome variable was major adverse cardiovascular and cerebrovascular events (MACCEs) that consisted of cardiovascular death, nonfatal myocardial infarction, coronary revascularisation, and nonfatal ischemic stroke. RESULTS: At a median follow-up of 5.8 years, 20 statin users and 17 controls (7.4 and 5.6 events/1,000 person-year, respectively; hazard ratio [HR) 1.04; p=0.92) experienced MACCE. Kaplan-Meier curves showed similar MACCE rates in both groups (p=0.91). In separate analyses for persons with normal (p=0.29) or near normal coronary arteries (p=0.67), MACCE rates did not differ between the groups. Age (HR 1.04; p=0.044), male sex (HR 3.06, p=0.018), and smoking (HR 2.87, p=0.019) were independently associated with MACCEs. In subgroup analyses, no significant factors affected the relationship between statin use and MACCEs. CONCLUSIONS: Statin use was not associated with cardiovascular risk reduction in high-risk persons with normal or near normal coronary arteries. More individualised lipid-lowering therapy may benefit this population.

The effect of polycyclic aromatic hydrocarbons on changes in the brain structure of firefighters: An analysis using data from the Firefighters Research on Enhancement of Safety & Health study.

Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion of organic matter, and firefighters are highly exposed to these toxic compounds at fire sites. Exposure to PAHs can cause cognitive decline and neurodegeneration; however, to date, few studies have examined the potential effects of PAH exposure on structural changes in the brain. We aimed to investigate the association between the four types of PAH metabolites and the corresponding changes in neuroimaging markers based on smoking status and hypertension in male firefighters. For this, we utilized the 2-year follow-up data of 301 Korean male firefighters aged over 40 years. The concentrations of four PAH metabolites in urine were measured. Subcortical volume and cortical thickness were estimated using 3 T magnetic resonance imaging of the brain. A generalized linear model was used to investigate the effects of PAHs on changes in the subcortical volume and cortical thickness. We found an association between 1-hydroxyphenathrene (1-OHPHE) and 2-hydroxyfluorene (2-OHF) and changes in several brain regions in all the study participants. Individuals who had never smoked showed significantly thinner frontal (p < 0.001), parietal (p < 0.001), temporal (p < 0.001), and cingulate lobes (p < 0.001) with 1% increase each in the urinary concentration of 1-OHPHE. Hypertension interacted with the concentration of 1-OHPHE to reduce the volume of gray matter and cause cortical thinning in the frontal, parietal, and temporal lobes. Exposure to PAHs may reduce cortical thickness and subcortical volume, which are definitive markers of neurodegeneration. Notably, hypertension can accelerate the degenerative effects of PAHs.

LncRNA HSPA7 in human atherosclerotic plaques sponges miR-223 and promotes the proinflammatory vascular smooth muscle cell transition.

Although there are many genetic loci in noncoding regions associated with vascular disease, studies on long noncoding RNAs (lncRNAs) discovered from human plaques that affect atherosclerosis have been highly limited. We aimed to identify and functionally validate a lncRNA using human atherosclerotic plaques. Human aortic samples were obtained from patients who underwent aortic surgery, and tissues were classified according to atherosclerotic plaques. RNA was extracted and analyzed for differentially expressed lncRNAs in plaques. Human aortic smooth muscle cells (HASMCs) were stimulated with oxidized low-density lipoprotein (oxLDL) to evaluate the effect of the identified lncRNA on the inflammatory transition of the cells. Among 380 RNAs differentially expressed between the plaque and control tissues, lncRNA HSPA7 was selected and confirmed to show upregulated expression upon oxLDL treatment. HSPA7 knockdown inhibited the migration of HASMCs and the secretion and expression of IL-1ß and IL-6; however, HSPA7 knockdown recovered the oxLDL-induced reduction in the expression of contractile markers. Although miR-223 inhibition promoted the activity of Nf-κB and the secretion of inflammatory proteins such as IL-1ß and IL-6, HSPA7 knockdown diminished these effects. The effects of miR-223 inhibition and HSPA7 knockdown were also found in THP-1 cell-derived macrophages. The impact of HSPA7 on miR-223 was mediated in an AGO2-dependent manner. HSPA7 is differentially increased in human atheroma and promotes the inflammatory transition of vascular smooth muscle cells by sponging miR-223. For the first time, this study elucidated the molecular mechanism of action of HSPA7, a lncRNA of previously unknown function, in humans.

Characterization of Ferric Chloride-Induced Arterial Thrombosis Model of Mice and the Role of Red Blood Cells in Thrombosis Acceleration.

PURPOSE: The ferric chloride (FeCl3)-induced thrombosis model is widely used for thrombosis research. However, it lacks standardization with uncertainty in the exact mechanism of thrombosis. This study aimed to characterize thrombus formation in a mouse model. MATERIALS AND METHODS: We investigated thrombus formation and stability using various FeCl3 concentrations (10%, 20%, 30%, 40%, and 50%, w/v) in carotid arteries of the Institute of Cancer Research (ICR) and C57BL/6N mice using the FeCl3-induced thrombosis model. We also investigated thrombus histopathology using immunohistochemistry and electron microscopy. RESULTS: Higher FeCl3 concentrations induced dose-dependent, faster, larger, and more stable thrombus formation in both strains of mice. However, the ICR mice showed better dose-responses in thrombus formation and stability compared to the C57BL/6N mice. Thrombi were fibrin- and platelet-rich without significant changes across FeCl3 concentrations. However, the content of red blood cells (RBCs) increased with increasing FeCl3 concentrations (p for trend <0.001) and inversely correlated with time to occlusion (r=-0.65, p<0.001). While platelets and fibrin were evenly distributed over the thrombus, RBCs were predominantly located near the FeCl3 treatment area. Transmission electron microscopy showed that RBCs attached to and were surrounded by aggregates of degranulated platelets, suggesting their potential role in platelet activation. CONCLUSION: Faster and larger thrombus formation is induced in a dose-dependent manner by a wide range of FeCl3 concentrations, but the stable thrombus formation requires higher FeCl3 concentrations. Mouse strain affects thrombus formation and stability. RBCs and their interaction with platelets play a key role in the acceleration of FeCl3-induced thrombosis.

High-Throughput Cell Concentration Using A Piezoelectric Pump in Closed-Loop Viscoelastic Microfluidics.

Cell concentration is a critical process in biological assays and clinical diagnostics for the pre-treatment of extremely rare disease-related cells. The conventional technique for sample preconcentration and centrifugation has the limitations of a batch process requiring expensive and large equipment. Therefore, a high-throughput continuous cell concentration technique needs to be developed. However, in single-pass operation, the required concentration ratio is hard to achieve. In this study, we propose a closed-loop continuous cell concentration system using a viscoelastic non-Newtonian fluid. For miniaturized and integrated systems, two piezoelectric pumps were adopted. The pumping capability generated by a piezoelectric pump in a microfluidic channel was evaluated depending on the applied voltage, frequency, sample viscosity, and channel length. The concentration performance of the device was evaluated using 13 µm particles and white blood cells (WBCs) with different channel lengths and voltages. In the closed-loop system, the focused cells collected at the center outlet were sent back to the inlet, while the buffer solution was removed to the side outlets. Finally, to expand the clinical applicability of our closed-loop system, WBCs in lysed blood samples with 70% hematocrit and prostate cancer cells in urine samples were used. Using the closed-loop system, WBCs were concentrated by ~63.4 ± 0.8-fold within 20 min to a final volume of 160 µL using 10 mL of lysed blood sample with 70% hematocrit (~3 cP). In addition, prostate cancer cells in 10 mL urine samples were concentrated by ~64.1-fold within ~11 min due to low viscosity (~1 cP).

Regional differences in office and self-measured home heart rates in Asian hypertensive patients: AsiaBP@Home study.

Increased heart rate is a predictor of cardiovascular disease, heart failure, and all-cause mortality. In those with high heart rates, interventions for heart rate reduction have been associated with reductions in coronary events. Asia is a diverse continent, and the prevalences of hypertension and cardiovascular disease differ among its countries. The present analysis of AsiaBP@Home study data investigated differences among resting heart rates (RHRs) in 1443 hypertensive patients from three Asian regions: East Asia (N = 595), Southeast Asia (N = 680), and South Asia (N = 168). This is the first study to investigate self-measured RHR values in different Asian countries/regions using the same validated home BP monitoring device (Omron HEM-7130-AP/HEM-7131-E). Subjects in South Asia had higher RHR values compared with the other two regions, and the regional tendency found in RHR values was different from that found in BP values. Even after adjusting for age, sex, BMI, habitual alcohol consumption, current smoking habit, shift worker, hyperlipidemia, diabetes, chronic kidney disease, history of heart failure, and beta-blocker use, both office and home RHR values in South Asia were the highest among Asia (mean values ± SE of office: East Asia [E] 75.2 ± 1.5 bpm, Southeast Asia [Se] 76.7 ± 1.5 bpm, South Asia [S] 81.9 ± 1.4 bpm; home morning: [E] 69.0 ± 1.2 bpm, [Se] 72.9 ± 1.2 bpm, [S] 74.9 ± 1.1 bpm; home evening: [E] 74.6 ± 1.2 bpm, [Se] 78.3 ± 1.2 bpm, [S] 83.8 ± 1.1 bpm). Given what is known about the impact of RHR on heart disease, our findings suggest the possible benefit of regionally tailored clinical strategies for cardiovascular disease prevention.

Disparities in Mortality and Cardiovascular Events by Income and Blood Pressure Levels Among Patients With Hypertension in South Korea.

Background Socioeconomic status is associated with differences in risk factors of cardiovascular disease and increased risks of cardiovascular disease and mortality. However, it is unclear whether an association exists between cardiovascular disease and income, a common measure of socioeconomic status, among patients with hypertension. Methods and Results This population-based longitudinal study comprised 479 359 patients aged ≥19 years diagnosed with essential hypertension. Participants were categorized by income and blood pressure levels. Primary end point was all-cause and cardiovascular mortality and secondary end points were cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Low income was significantly associated with high all-cause (hazard ratio [HR], 1.26; 95% CI, 1.23-1.29, lowest versus highest income) and cardiovascular mortality (HR, 1.31; 95% CI, 1.25-1.38) as well as cardiovascular events (HR, 1.07; 95% CI, 1.05-1.10) in patients with hypertension after adjusting for age, sex, systolic blood pressure, body mass index, smoking status, alcohol consumption, physical activity, fasting glucose, total cholesterol, and the use of aspirin or statins. In each blood pressure category, low-income levels were associated with high all-cause and cardiovascular mortality and cardiovascular events. The excess risks of all-cause and cardiovascular mortality and cardiovascular events associated with uncontrolled blood pressure were more prominent in the lowest income group. Conclusions Low income and uncontrolled blood pressure are associated with increased all-cause and cardiovascular mortality and cardiovascular events in patients with hypertension. These findings suggest that income is an important aspect of social determinants of health that has an impact on cardiovascular outcomes in the care of hypertension.

Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study.

We sought to assess the association between common antihypertensive drugs and the risk of incident cancer in treated hypertensive patients. Using the Korean National Health Insurance Service database, the risk of cancer incidence was analyzed in patients with hypertension who were initially free of cancer and used the following antihypertensive drug classes: Angiotensin-converting enzyme inhibitors (ACEIs); angiotensin receptor blockers (ARBs); beta blockers (BBs); calcium channel blockers (CCBs); and diuretics. During a median follow-up of 8.6 years, there were 4513 (6.4%) overall cancer incidences from an initial 70,549 individuals taking antihypertensive drugs. ARB use was associated with a decreased risk for overall cancer in a crude model (hazard ratio (HR): 0.744, 95% confidence interval (CI): 0.696-0.794) and a fully adjusted model (HR: 0.833, 95% CI: 0.775-0.896) compared with individuals not taking ARBs. Other antihypertensive drugs, including ACEIs, CCBs, BBs, and diuretics, did not show significant associations with incident cancer overall. The long-term use of ARBs was significantly associated with a reduced risk of incident cancer over time. The users of common antihypertensive medications were not associated with an increased risk of cancer overall compared to users of other classes of antihypertensive drugs. ARB use was independently associated with a decreased risk of cancer overall compared to other antihypertensive drugs.

Adherence to Antihypertensive Medication and Incident Cardiovascular Events in Young Adults With Hypertension.

[Figure: see text].

Effect of angiotensin receptor blockers on the development of cancer: A nationwide cohort study in korea.

The potential cancer risk associated with long-term exposure to angiotensin receptor blockers (ARBs) is still unclear. We assessed the risk of incident cancer among hypertensive patients who were treated with ARBs compared with patients exposed to angiotensin-converting enzyme inhibitors (ACEIs), which are known to have a neutral effect on cancer development. Using the Korean National Health Insurance Service database, we analyzed the data of patients diagnosed with essential hypertension from January 2005 to December 2012 who were aged ≥40 years, initially free of cancer, and were prescribed either ACEI or ARB (n = 293,962). Cox proportional hazard model adjusted for covariates was used to evaluate the risk of incident cancer. During a mean follow-up of 10 years, 24,610 incident cancers were observed. ARB use was associated with a decreased risk of overall cancer compared with ACEI use (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.72-0.80). Similar results were obtained for lung (HR 0.73, 95% CI 0.64-0.82), hepatic (HR 0.56, 95% CI 0.48-0.65), and gastric cancers (HR 0.74, 95% CI 0.66-0.83). Regardless of the subgroup, greater reduction of cancer risk was seen among patients treated with ARB than that among patients treated with ACEIs. Particularly, the decreased risk of cancer among ARB users was more prominent among males and heavy drinkers (interaction P < .005). Dose-response analyses demonstrated a gradual decrease in risk with prolonged ARB therapy than that with ACEI use. In conclusion, ARB use was associated with a decreased risk of overall cancer and several site-specific cancers.

Soluble Urokinase-Type Plasminogen Activator Receptor, Changes of 24-Hour Blood Pressure, and Progression of Chronic Kidney Disease.

Background Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24-hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC-HI (Cardiovascular and Metabolic Disease Etiology Research Center-High Risk) cohort study (2013-2018). The relationship of serum suPAR levels to 24-hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2-2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m2 at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24-hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27-6.76; P=0.01). During a follow-up of 43.2 (interquartile range, 27.0-55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37-3.21; P=0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02-2.01; P=0.03) with every 1-unit increase in serum suPAR levels. Conclusions Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.

Associations between social network properties and metabolic syndrome and the mediating effect of physical activity: findings from the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) Cohort.

INTRODUCTION: Social isolation and loneliness are positively associated with metabolic syndrome. However, the mechanisms by which social isolation affects metabolic syndrome are not well understood. RESEARCH DESIGN AND METHODS: This study was designed as a cross-sectional study of baseline results from the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) Cohort. We included 10 103 participants (8097 community-based low-risk participants, 2006 hospital-based high-risk participants) from the CMERC Cohort. Participants aged 65 years or older were excluded. Multiple imputation by chained equations was applied to impute missing variables. The quantitative properties of social networks were assessed by measuring the 'size of social networks'; qualitative properties were assessed by measuring the 'social network closeness'. Metabolic syndrome was defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariate logistic regression analyses were conducted to assess association between social network properties and metabolic syndrome. The mediating effects of physical inactiveness, alcohol consumption, cigarette smoking and depressive symptoms were estimated. Age-specific effect sizes were estimated for each subgroup. RESULTS: A smaller social network was positively associated with higher prevalences of metabolic syndrome in all subgroups, except the high-risk male subgroup. There was no clear association between social network closeness and metabolic syndrome. In community-based participants, an indirect effect through physical activity was detected in both sexes; however, in hospital-based participants, no indirect effects were detected. Cigarette smoking, alcohol consumption and depression did not mediate the association. Age-specific estimates showed that the indirect effect through physical activity had a greater impact in older participants. CONCLUSIONS: A smaller social network is positively associated with metabolic syndrome. This trend could be partially explained by physical inactivity, especially in older individuals.

Atorvastatin protects cardiomyocyte from doxorubicin toxicity by modulating survivin expression through FOXO1 inhibition.

BACKGROUND: Survivin has an anti-apoptotic effect against anthracycline-induced cardiotoxicity. Clinically, statin use is associated with a lower risk for heart failure in breast cancer patients with anthracycline chemotherapy. So, the purpose of our study was to investigate whether survivin mediates the protective effect of statin against anthracycline-induced cardiotoxicity. METHODS: Mice were treated once a week with 5 mg/kg doxorubicin for 4 weeks with or without atorvastatin 20 mg/kg every day then heart tissues were analyzed. Molecular and cellular biology analyses were performed with H9c2 cell lysates. RESULTS: Doxorubicin suppressed survivin expression via activation of FOXO1 in H9c2 cardiomyocytes. Whereas, atorvastatin inhibited FOXO1 by increasing phosphorylation and inhibiting nuclear localization. Doxorubicin induced FOXO1 binding to STAT3 and prevented STAT3 from interacting with Sp1. However, atorvastatin inhibited these interactions and stabilized STAT3/Sp1 transcription complex. Chromatin immunoprecipitation analysis demonstrated that doxorubicin decreased STAT3/Sp1 complex binding to survivin promoter, whereas atorvastatin stabilized this binding. In mouse model, atorvastatin rescued doxorubicin-induced reduction of survivin expression and of heart function measured by cardiac magnetic resonance imaging. CONCLUSIONS: Our study suggested a new pathophysiologic mechanism that survivin mediated protective effect of atorvastatin against doxorubicin-induced cardiotoxicity via FOXO1/STAT3/Sp1 transcriptional network.