Left ventricular structure and function in relation to sodium dietary intake and renal handling in untreated Chinese patients.

Whether left ventricular structure and function is associated with sodium dietary intake and renal handling while considering blood pressure (BP) remains unclear. Consecutive untreated patients referred for ambulatory BP monitoring were recruited. Standard echocardiography was performed to measure left ventricular structure and function. Fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa) were calculated as markers of proximal and distal tubular sodium handling, respectively. The 952 participants (51.0% women; mean age, 50.8 years) included 614 (64.5%) ambulatory hypertension and 103 (10.8%) left ventricular hypertrophy. There were significant interactions of urinary sodium excretion with FELi (P ≤ 0.045), but not FDRNa (P ≥ 0.36), in relation to left ventricular posterior wall thickness (LVPW), mass (LVM) and mass index (LVMI), but not functional measurements. Only in tertile 1 of FELi, the multivariate-adjusted regression coefficients for urinary sodium excretion reached statistical significance (P ≤ 0.049), being 0.16 ± 0.05 mm, 4.32 ± 1.48 g, and 1.64 ± 0.83 g/m2 for LVPW, LVM and LVMI, respectively. In mutually adjusted analyses, the regression coefficient for LVMI was statistically significant for FELi, FDRNa and 24-h systolic BP, being -2.17 ± 0.49, -1.95 ± 0.54, and 2.99 ± 0.51 g/m2, respectively (P < 0.001). Multivariable analysis of variance showed that sodium renal handling indexes (P ≥ 0.14), but not sodium urinary excretion (P = 0.007), were similarly as 24-h BP associated with LVMI. Heat maps on left ventricular hypertrophy provided a graphical confirmation of the findings. Sodium dietary intake and renal handling interact to be associated with left ventricular structure. Renal handling indexes were similarly in size as, jointly in action with and independently of 24-h BP.

An outcome-driven threshold for pulse pressure amplification.

Pulse pressure amplification (PPA) is the brachial-to-aortic pulse pressure ratio and decreases with age and cardiovascular risk factors. This individual-participant meta-analysis of population studies aimed to define an outcome-driven threshold for PPA. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n = 5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement. Age ranged from 30 to 96 years (median 53.6). Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA < 1.3 vs ≥1.3 were 1.54 (95% confidence interval [CI]: 1.00-2.36) and 2.45 (CI: 1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs ≥60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. The proportion of high-risk women (PPA < 1.3) was higher at younger age (<60 vs ≥60 years: 67.7% vs 61.5%; P < 0.001). In conclusion, over and beyond common risk factors, a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular coronary complications and is an underestimated risk factor in women aged 30-60 years. Our study supports pulse wave analysis for risk stratification.

Clinical characteristics of primary aldosteronism screened from Chinese patients with hypertension: The China primary aldosteronism prospective study.

We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone-to-renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non-diagnosed PA (n = 147) were 4.54 (95% CI: 2.78-7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64-0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63-3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90-4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20-2.86) for a 0.3 mmol/l higher serum high-density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

Lead-associated mortality in the US 1999-2020: a time-stratified analysis of a national cohort.

OBJECTIVES: We undertook time-stratified analyses of the National Health and Nutrition Examination Survey in the US to assess time trends (1999-2020) in the associations of blood lead (BL) with blood pressure, mortality, the BL-associated population attributable fraction (PAF). METHODS: Vital status of participants, 20-79 years old at enrolment, was ascertained via the National Death Index. Regressions, mediation analyses and PAF were multivariable adjusted and standardized to 2020 US Census data. RESULTS: In time-stratified analyses, BL decreased from 1.76 µg/dl in 1999-2004 to 0.93 µg/dl in 2017-2020, while the proportion of individuals with BL < 1 µg/dl increased from 19.2% to 63.0%. Total mortality was unrelated to BL (hazard ratio (HR) for a fourfold BL increment: 1.05 [95% confidence interval, CI: 0.93-1.17]). The HR for cardiovascular death was 1.44 (1.01-2.07) in the 1999-2000 cycle, but lost significance thereafter. BL was directly related to cardiovascular mortality, whereas the indirect BL pathway via BP was not significant. Low socioeconomic status (SES) was directly related to BL and cardiovascular mortality, but the indirect SES pathway via BL lost significance in 2007-2010. From 1999-2004 to 2017-2020, cardiovascular PAF decreased ( P  < 0.001) from 7.80% (0.17-14.4%) to 2.50% (0.05-4.68%) and number of lead-attributable cardiovascular deaths from 53 878 (1167-99 253) to 7539 (160-14 108). CONCLUSION: Due to implementation of strict environmental policies, lead exposure is no longer associated with total mortality, and the mildly increased cardiovascular mortality is not associated with blood lead via blood pressure in the United States.

New-onset hypertension as a contributing factor to the incidence of atrial fibrillation in the elderly.

Hypertension and atrial fibrillation are closely related. However, hypertension is already prevalent in young adults, but atrial fibrillation usually occurs in the elderly. In the present analysis, we investigated incident atrial fibrillation in relation to new-onset hypertension in an elderly Chinese population. Our study participants were elderly (≥65 years) hypertensive residents, recruited from community health centers in the urban Shanghai (n = 4161). Previous and new-onset hypertension were defined as the use of antihypertensive medication or elevated systolic/diastolic blood pressure (≥140/90 mmHg), respectively, at entry and during follow-up on ≥ 2 consecutive clinic visits. Atrial fibrillation was detected by a 30-s single-lead electrocardiography (ECG, AliveCor® Heart Monitor) and further evaluated with a regular 12-lead ECG. During a median of 2.1 years follow-up, the incidence rate of atrial fibrillation was 7.60 per 1000 person-years in all study participants; it was significantly higher in patients with new-onset hypertension (n = 368) than those with previous hypertension (n = 3793, 15.76 vs. 6.77 per 1000 person-years, P = 0.02). After adjustment for confounding factors, the hazard ratio for the incidence of atrial fibrillation was 2.21 (95% confidence interval 1.15-4.23, P = 0.02) in patients with new-onset hypertension versus those with previous hypertension. The association was even stronger in those aged ≥ 75 years (hazard ratio 2.70, 95% confidence interval 1.11-6.56, P = 0.03). In patients with previous hypertension, curvilinear association (P for non-linear trend = 0.04) was observed between duration of hypertension and the risk of incident atrial fibrillation, with a higher risk in short- and long-term than mid-term duration of hypertension. Our study showed a significant association between new-onset hypertension and the incidence of atrial fibrillation in elderly Chinese. In an elderly Chinese population with previous and new-onset hypertension, we found that the new-onset hypertension during follow-up, compared with previous hypertension, was associated with a significantly higher risk of incident atrial fibrillation. In patients with previous hypertension, curvilinear association was observed between duration of hypertension and the risk of incident atrial fibrillation, with a higher risk in short- and long-term than mid-term duration of hypertension.

Obstructive sleep apnea in relation to beat-to-beat, reading-to-reading, and day-to-day blood pressure variability.

We investigated blood pressure (BP) variability as assessed by beat-to-beat, reading-to-reading and day-to-day BP variability indices in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). In 786 hospitalized hypertensives (mean age, 53.2 years; 42.2% women), we performed 10-min beat-to-beat (n = 705), 24-h ambulatory (n = 779), and 7-day home BP (n = 445) measurements and the full overnight polysomnography. Mild, moderate and severe OSAHS were defined as an apnea-hypopnea index of 5-14, 15-29, and ≥ 30 events per hour, respectively. BP variability indices including variability independent of the mean (VIM), average real variability (ARV), and maximum-minimum difference (MMD), were compared across the OSAHS severity groups. In univariate analysis, beat-to-beat systolic VIM and MMD, reading-to-reading asleep systolic and diastolic ARV and MMD increased from patients without OSAHS, to patients with mild, moderate and severe OSAHS. This increasing trend for beat-to-beat systolic VIM and MMD remained statistically significant after adjustment for confounders (P ≤ 0.047). There was significant (P ≤ 0.039) interaction of the presence and severity of OSAHS with age and body mass index in relation to the beat-to-beat systolic VIM and MMD and with the presence of diabetes mellitus in relation to asleep systolic ARV. The association was stronger in younger (age < 50 years) and obese (body mass index ≥ 28 kg/m²) and diabetic patients. None of the day-to-day BP variability indices reached statistical significance (P ≥ 0.16). BP variability, in terms of beat-to-beat systolic VIM and MMD and asleep reading-to-reading asleep systolic ARV, were higher with the more severe OSAHS, especially in younger and obese and diabetic patients.

Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis.

BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.

Seasonality in nighttime blood pressure and its associations with target organ damage.

There is some evidence that nighttime blood pressure varies between seasons. In the present analysis, we investigated the seasonal variation in ambulatory nighttime blood pressure and its associations with target organ damage. In 1054 untreated patients referred for ambulatory blood pressure monitoring, we performed measurements of urinary albumin-to-creatinine ratio (ACR, n = 1044), carotid-femoral pulse wave velocity (cfPWV, n = 1020) and left ventricular mass index (LVMI, n = 622). Patients referred in spring (n = 337, 32.0%), summer (n = 210, 19.9%), autumn (n = 196, 18.6%) and winter (n = 311, 29.5%) had similar 24-h ambulatory systolic/diastolic blood pressure (P ≥ 0.25). However, both before and after adjustment for confounding factors, nighttime systolic/diastolic blood pressure differed significantly between seasons (P < 0.001), being highest in summer and lowest in winter (adjusted mean values 117.0/75.3 mm Hg vs. 111.4/71.1 mm Hg). After adjustment for confounding factors, nighttime systolic/diastolic blood pressure were significantly and positively associated with ACR, cfPWV and LVMI (P < 0.006). In season-specific analyses, statistical significance was reached for all the associations of nighttime blood pressure with target organ damage in summer (P ≤ 0.02), and for some of the associations in spring, autumn and winter. The association between nighttime systolic blood pressure and ACR was significantly stronger in patients examined in summer than those in winter (standardized ß, 0.31 vs 0.11 mg/mmol, P for interaction = 0.03). In conclusion, there is indeed seasonality in nighttime blood pressure level, as well as in its association with renal injury in terms of urinary albumin excretion. Our study shows that there is indeed seasonal variability in nighttime blood pressure, highest in summer and lowest in winter, and its association with renal injury in terms of urinary albumin excretion varies between summer and winter as well.

Serum Galectin-3 and Mucin-1 (CA15-3) in Relation to Renal Function in Untreated Chinese Patients.

BACKGROUND: Galectin-3 is a multi-functional lectin protein and a ligand of mucin-1 (CA15-3), and has been linked to renal fibrosis in animal models and renal function in humans. However, no population study has ever explored the associations with both ligand and receptor. We therefore investigate the independent association of renal function with serum galectin-3 and mucin-1 (CA15-3) in untreated Chinese patients. METHODS: The study participants were outpatients who were suspected of hypertension, but had not been treated with antihypertensive medication. Serum galectin-3 and mucin-1 (CA15-3) concentrations were both measured by the enzyme-linked immunosorbent assay (ELISA) method. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine by the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: The 1,789 participants included 848 (47.4%) men. Mean (±SD) age was 51.3 ± 10.7 years. Multiple regression analyses showed that eGFR was significantly associated with serum galectin-3 and mucin-1 (CA15-3) concentration (0.68 and 1.32 ml/min/1.73 m2 decrease per 1-SD increase in log transformed serum galectin-3 and mucin-1 (CA15-3) concentration, respectively; P ≤ 0.006). The association of eGFR with serum mucin-1 (CA15-3) concentration was significantly stronger in the overweight (BMI 24.0-27.9 kg/m2) and obese (BMI ≥ 28.0 kg/m2) than in normal weight subjects (BMI < 24.0 kg/m2, P for interaction 0.018). Path analysis showed that serum galectin-3 concentration had both a direct (P = 0.016) and a mucin-1 mediated indirect effect (P = 0.014) on eGFR. CONCLUSIONS: Both circulating galectin-3 and mucin-1 (CA15-3) were significantly associated with renal function. The role of galectin-3 on renal function might be partially via mucin-1.

A prospective study on the association between atrial fibrillation and blood pressure in an elderly Chinese population.

BACKGROUND: Intensive blood pressure (BP) lowering in patients with hypertension has been associated with a lowered risk of atrial fibrillation (AF). It is still uncertain what is the optimal BP levels to prevent AF in the general elderly population. In the present prospective study, we investigated the association between incident AF and BP in an elderly Chinese population. METHODS AND FINDINGS: Elderly (≥65 years) residents were recruited from 6 communities in Shanghai. 9019 participants who did not have AF at baseline and had at least one ECG recording during follow-up were included in the present analysis. During a median of 3.5 years follow-up, the overall incidence rate of AF was 5.6 per 1000 person-years (n = 178). Systolic BP was associated with increased AF risk (age- and sex-adjusted hazard ratio [HR] per 20-mmHg increase for systolic BP 1.21, 95% CI 1.04-1.39, P = 0.01), but risk estimate was attenuated after adjustment for common AF risk factors. In categorical analyses, statistical significance was achieved for HR relative to optimal BP only in stage 2 or 3 systolic and diastolic hypertension (multivariate-adjusted HR 1.76, 95% CI 1.00-3.08, P = 0.05). The association between AF incidence and BP status tended to be stronger in the absence than presence of a history of cardiovascular disease at baseline (P for interaction = 0.06). CONCLUSION: In this Chinese population of 65 years and older, linear increases in systolic and diastolic BP were not independently associated with increased risk of AF, and only exposure to stage 2 or 3 hypertension carries a higher risk of AF.

Central hypertension is a non-negligible cardiovascular risk factor.

High blood pressure (BP) confers cardiovascular risk. However, the clinical value of central BP remains debatable. In this article, we aim to briefly review the prognosis, diagnosis, and treatment of central hypertension. Central and brachial BPs are closely correlated. In most prospective investigations, elevated central and peripheral BPs were similarly associated with adverse outcomes. Outcome-driven thresholds of the central systolic BP estimated by the type I device were on average 10 mmHg lower than their brachial counterparts. Cross-classification based on the central and brachial BPs identified that nearly 10% of patients had discrepancy in their status of central and brachial hypertension. Irrespective of the brachial BP status, central hypertension was associated with increased cardiovascular risk, highlighting the importance of central BP assessment in the management of hypertensive patients. Newer antihypertensive agents, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, were more efficacious than older agents in central BP reduction. Clinical trials are warranted to demonstrate whether controlling central hypertension with an optimized antihypertensive drug treatment will be beneficial beyond the control of brachial hypertension.

The prevalence of masked hypertension and masked uncontrolled hypertension in relation to overweight and obesity in a nationwide registry in China.

Masked hypertension is difficult to identify and is associated with adverse outcomes. How and to what extent masked hypertension is related to overweight and obesity remain unclear. In participants with a clinic blood pressure (BP) < 140/90 mmHg enrolled in a nationwide prospective registry in China, we performed ambulatory and home BP measurements and defined masked hypertension and masked uncontrolled hypertension as an elevated 24-h (≥130/80 mmHg), daytime (≥135/85 mmHg) or nighttime ambulatory BP (≥120/70 mmHg) or an elevated home BP (≥135/85 mmHg). Overweight and obesity were defined as a body mass index of 25.0-29.9 and ≥30.0 kg/m2, respectively. The 2838 participants had a mean (±SD) age of 54.9 ± 13.6 years and included 1286 (45.3%) men and 1065 (37.5%) and 173 (6.1%) patients with overweight and obesity, respectively. Multiple stepwise regression analyses identified that body mass index was significantly (P ≤ 0.006) associated with the prevalence of masked ambulatory and home hypertension in treated (n = 1694, 58.6% and 42.1%, respectively) but not untreated participants (n = 1144, 55.7% and 29.5%, respectively). In categorical analyses, significant associations were observed with overweight and obesity for the prevalence of masked uncontrolled ambulatory and home hypertension (P ≤ 0.02) but not masked ambulatory or home hypertension (P ≥ 0.08). The adjusted odds ratios (95% confidence intervals) for overweight and obesity relative to normal weight were 1.56 (1.27-1.92) and 1.34 (1.09-1.65) for masked uncontrolled ambulatory and home hypertension, respectively. In conclusion, overweight and obesity were associated with a higher prevalence of masked uncontrolled hypertension, indicating that clinic BP might overestimate antihypertensive treatment effects in patients with overweight and obesity.

Isolated nocturnal hypertension in relation to host and environmental factors and clock genes.

Isolated nocturnal hypertension (INH) is a special type of out-of-office hypertension. Its determinants and pathophysiology remain unclear. In a nested case-control study, we intend to investigate the host, environmental, and genetic factors in relation to INH. Among 2030 outpatients screened from December 2008 till June 2015, 128 patients with INH were identified, and then 128 normotensives were matched according to sex and age. INH was an elevated nocturnal blood pressure (BP ≥120/70 mmHg) in the presence of a normal daytime BP (< 135/85 mmHg). Host factors included age, sex, body mass index, smoking and drinking, sleep time and duration, heart rate, serum lipids, and serum creatinine. Environmental cues encompassed season, ambient temperature, atmospheric pressure, humidity, and wind speed, and genetic cues 29 single-nucleotide polymorphisms (SNPs) in 12 clock genes. Daytime and nighttime BPs averaged 124.9/80.7  and 114.5/73.7 mmHg, respectively, in the INH patients and 121.0/76.5 and 101.8/63.3 mmHg in the normotensive controls. Stepwise logistic regression analyses revealed that INH was associated with nighttime heart rate (P = .0018), sleep duration (P = .0499), and relative humidity (P = .0747). The odds ratios (95% CI) for each 10 beats/min faster nighttime heart rate and 10% lower relative humidity were 1.82 (1.25-2.65) and 0.82 (0.67-1.00), respectively. Irrespective of the genetic models, no significant association was observed between INH and the SNPs (P ≥ .054). In conclusion, INH was associated with host and environmental factors rather than genetic markers.

Changes in the CHA2DS2-VASC score as a predictor of incident atrial fibrillation in older Chinese individuals: the AF-CATCH study.

Aims: Incidence of atrial fibrillation is highly associated with age and cardiovascular co-morbidities. Given this relationship, we hypothesized that the dynamic changes resulting in an increase in the CHA2DS2-VASC score over time would improve the efficiency of predicting incident atrial fibrillation on repeated screening after a negative test. Methods and results: We investigated in an analysis of the AF-CATCH trial [quarterly vs. annual electrocardiogram (ECG) screening for atrial fibrillation in older Chinese individuals] data, the association between the changes in the CHA2DS2-VASC score from baseline to end-of-study visit and the risk of incident atrial fibrillation. Participants without a history of atrial fibrillation and with a sinus rhythm at baseline were randomized to the annual (usual) or quarterly 30 s (intensive) single-lead ECG screening groups. During a median follow-up of 2.1 years in 6806 participants, the incidence rate of atrial fibrillation increased from 4.2 per 1000 person-years in participants with a change in the CHA2DS2-VASC score of 0 to 6.4 and 25.8 per 1000 person-years in participants with a change in the CHA2DS2-VASC score of 1 and ≥2, respectively. A change in the CHA2DS2-VASC score of ≥2 was associated with a significantly elevated risk of incident atrial fibrillation. Conclusions: Patients with substantial changes in the CHA2DS2-VASC score were more likely to develop incident atrial fibrillation, and regular re-assessments of cardiovascular risk factors in the elderly are probably worthwhile to improve the detection of atrial fibrillation. Registration: URL: http://www.clinicaltrials.gov; Unique identifier: NCT02990741.

Microenvironment-driven sequential ferroptosis, photodynamic therapy, and chemotherapy for targeted breast cancer therapy by a cancer-cell-membrane-coated nanoscale metal-organic framework.

Designing and developing nanomedicine based on the tumor microenvironment (TME) for effective cancer treatment is highly desirable. In this work, polyvinyl pyrrolidone (PVP) dispersed nanoscale metal-organic framework (NMOF) of Fe-TCPP (TCPP = tetrakis (4-carboxyphenyl) porphyrin) loaded with hypoxia-activable prodrug tirapazamine (TPZ) and coated by the cancer cell membrane (CM) is constructed (the formed nanocomposite denoted as PFTT@CM). Due to the functionalization with the homologous cancer cell membrane, PFTT@CM is camouflaged to evade the immune clearance and preferentially accumulates at the tumor site. Once internalized by cancer cells, PFTT@CM is activated by the TME through redox reaction and Fenton reaction between Fe3+ in nano-platform and endogenous glutathione (GSH) and hydrogen peroxide (H2O2) to promote GSH exhausting as well as •OH and O2 production, which triggers ferroptosis and dramatically enhances photodynamic therapy (PDT) efficacy. Subsequently, the PDT process mediated by TCPP and light would consume oxygen and aggravate tumor hypoxia to further activate the prodrug TPZ for cancer chemotherapy. As a consequence, the TME-driven PFTT@CM nano-platform not only demonstrated its TME modulation ability but also showed a sequential synergistic therapy, which eventually inhibited the cancer cell proliferation. This multimodal nano-platform is expected to shed light on the design of TME-activatable reaction to reinforce the synergistic therapeutic outcome and facilitate the development of effective cancer nanomedicine.

Risk Stratification by Cross-Classification of Central and Brachial Systolic Blood Pressure.

BACKGROUND: Whether cardiovascular risk is more tightly associated with central (cSBP) than brachial (bSBP) systolic pressure remains debated, because of their close correlation and uncertain thresholds to differentiate cSBP into normotension versus hypertension. METHODS: In a person-level meta-analysis of the International Database of Central Arterial Properties for Risk Stratification (n=5576; 54.1% women; mean age 54.2 years), outcome-driven thresholds for cSBP were determined and whether the cross-classification of cSBP and bSBP improved risk stratification was explored. cSBP was tonometrically estimated from the radial pulse wave using SphygmoCor software. RESULTS: Over 4.1 years (median), 255 composite cardiovascular end points occurred. In multivariable bootstrapped analyses, cSBP thresholds (in mm Hg) of 110.5 (95% CI, 109.1-111.8), 120.2 (119.4-121.0), 130.0 (129.6-130.3), and 149.5 (148.4-150.5) generated 5-year cardiovascular risks equivalent to the American College of Cardiology/American Heart Association bSBP thresholds of 120, 130, 140, and 160. Applying 120/130 mm Hg as cSBP/bSBP thresholds delineated concordant central and brachial normotension (43.1%) and hypertension (48.2%) versus isolated brachial hypertension (5.0%) and isolated central hypertension (3.7%). With concordant normotension as reference, the multivariable hazard ratios for the cardiovascular end point were 1.30 (95% CI, 0.58-2.94) for isolated brachial hypertension, 2.28 (1.21-4.30) for isolated central hypertension, and 2.02 (1.41-2.91) for concordant hypertension. The increased cardiovascular risk associated with isolated central and concordant hypertension was paralleled by cerebrovascular end points with hazard ratios of 3.71 (1.37-10.06) and 2.60 (1.35-5.00), respectively. CONCLUSIONS: Irrespective of the brachial blood pressure status, central hypertension increased cardiovascular and cerebrovascular risk indicating the importance of controlling central hypertension.

Alcohol consumption in relation to the incidence of atrial fibrillation in an elderly Chinese population.

BACKGROUND: Alcohol consumption is a known modifiable risk factor for atrial fibrillation. The association, however, might differ according to gender. We investigated gender-specific associations between alcohol consumption and incident atrial fibrillation in an elderly Chinese population. METHODS: Our study participants were elderly residents (≥ 65 years) recruited from five community health centers in the urban area of Shanghai (n = 6,618). Alcohol intake was classified as never drinkers and current light-to-moderate (< 40 g/day) and heavy drinkers (≥ 40 g/day). Atrial fibrillation was detected by a 30-s single-lead electrocardiography (ECG, AliveCor® Heart Monitor) and further evaluated with a regular 12-lead ECG. RESULTS: During a median of 2.1 years (interquartile range: 2.0-2.2) follow-up, the incidence rate of atrial fibrillation was 1.10% in all study participants. It was slightly but non-significantly higher in men (n = 2849) than women (n = 3769, 1.30% vs. 0.96%, P = 0.19) and in current drinkers (n = 793) than never drinkers (n = 5825, 1.64% vs. 1.03%,P = 0.12). In both unadjusted and adjusted analyses, there was interaction between sex and current alcohol intake in relation to the incidence of atrial fibrillation (P < 0.0001). After adjustment for confounding factors, current drinkers had a significantly higher incidence rate of atrial fibrillation than never drinkers in women (12.96% [7/54] vs. 0.78% [29/3715], adjusted odds ratio [OR] = 10.25, 95% confidence interval [CI]: 3.54-29.67,P < 0.0001), but not in men (0.81% [6/739] vs. 1.47% [31/2110], OR = 0.62, 95% CI: 0.25-1.51,P = 0.29). CONCLUSIONS: Our study showed a significant association between alcohol intake and the incidence of atrial fibrillation in elderly Chinese women, but not men.

Clinic and ambulatory blood pressure in relation to the interaction between plasma advanced glycation end products and sodium dietary intake and renal handling.

Advanced glycation end product (AGE) clearance may cause renal tubular injuries, such as changes in sodium reabsorption. We hypothesize that AGEs interact with sodium metabolism to influence blood pressure (BP). The study participants were outpatients who were suspected of having hypertension but had not been treated with antihypertensive medication. Clinic and ambulatory blood pressures were measured at baseline (n = 989) and during follow-up (median, 4.4 years, n = 293). Plasma AGE concentrations were measured by enzyme-linked immunosorbent assay. Twenty-four-hour urine was collected for measurements of creatinine, sodium and lithium. In a cross-sectional analysis (n = 989), subjects in the top quintile versus quintiles 1-4 of plasma AGE concentration had significantly (P ≤ 0.004) lower fractional excretion of lithium (18.3% vs. 21.6%) and fractional distal reabsorption rate of sodium (95.0% vs. 95.8%) but similar BP (P ≥ 0.25). However, there was an interaction between plasma AGE concentration and urinary sodium excretion in relation to diastolic BP (P ≤ 0.058). Only in participants with low urinary sodium chloride excretion (≤6 grams/day, n = 189), clinic (84.3 vs. 80.2 mmHg), 24-h (83.9 vs. 80.4 mmHg), daytime (87.8 vs. 84.8 mmHg) and nighttime (75.1 vs. 72.1 mmHg) diastolic BP at baseline were higher (P ≤ 0.05) in the top quintile than in quintiles 1-4 of plasma AGE concentration. In the longitudinal study (n = 383), similar trends were observed, with significant (P ≤ 0.05) differences in the increment in daytime diastolic BP (6.8 vs. -1.7 mmHg) and incidence of ambulatory and treated hypertension (hazard ratio 3.73) during follow-up. In conclusion, AGEs were associated with high BP, probably via enhanced proximal sodium handling and on low dietary sodium intake.