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.

OSTEO18, a novel urinary proteomic signature, associated with osteoporosis in heart transplant recipients.

Background: Immunosuppressive treatment in heart transplant (HTx) recipient causes osteoporosis. The urinary proteomic profile (UPP) includes peptide fragments derived from the bone extracellular matrix. Study aims were to develop and validate a multidimensional UPP biomarker for osteoporosis in HTx patients from single sequenced urinary peptides identifying the parent proteins. Methods: A single-center HTx cohort was analyzed. Urine samples were measured by capillary electrophoresis coupled with mass spectrometry. Cases with osteoporosis and matching controls were randomly selected from all available 389 patients. In derivation case-control dataset, 1576 sequenced peptides detectable in ≥30 % of patients. Applying statistical analysis on these, an 18-peptide multidimensional osteoporosis UPP biomarker (OSTEO18) was generated by support vector modeling. The 2 replication datasets included 118 and 94 patients. For further validation, the whole cohort was analyzed. Statistical methods included logistic regression and receiver operating characteristic curve (ROC) analysis. Results: In derivation dataset, the AUC, sensitivity and specificity of OSTEO18 were 0.83 (95 % CI: 0.76-0.90), 74.3 % and 87.1 %, respectively. In replication datasets, results were confirmatory. In the whole cohort (154 osteoporotic patients [39.6 %]), the ORs for osteoporosis increased (p < 0.0001) across OSTEO18 quartiles from 0.39 (95 % CI: 0.25-0.61) to 3.14 (2.08-4.75). With full adjustment for known osteoporosis risk factors, OSTEO18 improved AUC from 0.708 to 0.786 (p = 0.0003) for OSTEO18 categorized (optimized threshold: 0.095) and to 0.784 (p = 0.0004) for OSTEO18 as continuously distributed classifier. Conclusion: OSTEO18 is a clinically meaningful novel biomarker indicative of osteoporosis in HTx recipients and is being certified as in-vitro diagnostic.

Seasonal variation in ambulatory blood pressure control in patients on clinic blood pressure-guided antihypertensive treatment.

BACKGROUND: We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment. METHODS: The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5 mg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30 mg/day, with the possible up-titration to amlodipine 10 mg/day or nifedipine-GITS 60 mg/day at 4 weeks of follow-up. RESULTS: The proportion of up-titration to higher dosages of antihypertensive drugs at 4 weeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n  = 302) than those who commenced treatment in spring/summer ( n  = 199, 24.5 vs. 12.0%, P  < 0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P  = 0.003) and 8 weeks of follow-up (52.5 vs. 74.9%, P  < 0.001). At 8 weeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8 mmHg) but greater nighttime SBP/DBP reduction (3.6/1.6 mmHg). Accordingly, at 8 weeks, the prevalence of nondippers was significantly ( P  < 0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%). CONCLUSION: Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial.

BACKGROUND: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. METHODS: In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. RESULTS: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). CONCLUSIONS: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Alcohol Consumption and Antihypertensive Treatment Effect in Male Patients With Hypertension.

BACKGROUND: Alcohol consumption is a proven risk factor of hypertension. In the present analysis, we investigated the use of antihypertensive medications and blood pressure control in male alcohol drinkers and non-drinkers with hypertension (systolic/diastolic blood pressure 160-199/100-119 mm Hg). METHODS: The study participants were patients enrolled in a 12-week therapeutic study and treated with the irbesartan/hydrochlorothiazide combination 150/12.5 mg once daily, with the possible up-titration to 300/12.5 mg/day and 300/25 mg/day at 4 and 8 weeks of follow-up, respectively, for blood pressure control of <140/90 mm Hg or <130/80 mm Hg in patients with diabetes mellitus. Alcohol consumption was classified as non-drinkers and drinkers. RESULTS: The 68 alcohol drinkers and 168 non-drinkers had similar systolic/diastolic blood pressure at baseline (160.8 ±â€…12.1/99.8 ±â€…8.6 vs. 161.8 ±â€…11.0/99.2 ±â€…8.6, P ≥ 0.55) and other characteristics except for current smoking (80.9% vs. 47.6%, P < 0.0001). In patients who completed the 12-week follow-up (n = 215), the use of higher dosages of antihypertensive drugs was similar at 4 weeks of follow-up in drinkers and non-drinkers (10.6% vs. 12.4%, P = 0.70), but increased to a significantly higher proportion in drinkers than non-drinkers at 12 weeks of follow-up (54.7% vs. 36.6%, P = 0.01). The control rate of hypertension tended to be lower in alcohol drinkers, compared with non-drinkers, at 4 weeks of follow-up (45.6% vs. 58.9%, P = 0.06), but became similar at 12 weeks of follow-up (51.5% vs. 54.8%, P = 0.65). CONCLUSION: Alcohol drinkers compared with non-drinkers required a higher dosage of antihypertensive drug treatment to achieve similar blood pressure control. CLINICAL TRIAL REGISTRY NUMBER: NCT00670566 at www.clinicaltrials.gov.

Current and recent cigarette smoking in relation to cardiovascular and non-cardiovascular mortality in an elderly male Chinese population.

OBJECTIVE: To investigate the association between current and former smoking and the risk of mortality in elderly Chinese men. METHODS: Our study participants were elderly (≥ 60 years) men recruited in a suburban town of Shanghai. Cigarette smoking status was categorized as never smoking, remote (cessation > 5 years) and recent former smoking (cessation ≤ 5 years), and light-to-moderate (≤ 20 cigarettes/day) and heavy current smoking (> 20 cigarettes/day). Cox proportional hazards models and restricted cubic splines were used to examine the associations of interest. RESULTS: The 1568 participants had a mean age of 68.6 ± 7.1 years. Of all participants, 311 were never smokers, 201 were remote former smokers, 133 were recent former smokers, 783 were light-to-moderate current smokers and 140 were heavy current smokers. During a median follow-up of 7.9 years, all-cause, cardiovascular and non-cardiovascular deaths occurred in 267, 106 and 161 participants, respectively. Heavy current smokers had the highest risk of all-cause and non-cardiovascular mortality, with an adjusted hazard ratio (HR) of 2.30 (95% CI: 1.34-4.07) and 3.98 (95% CI: 2.03-7.83) versus never smokers, respectively. Recent former smokers also had a higher risk of all-cause (HR = 1.62, 95% CI: 1.04-2.52) and non-cardiovascular mortality (HR = 2.40, 95% CI: 1.32-4.37) than never smokers. Cox regression restricted cubic spline models showed the highest risk of all-cause and non-cardiovascular mortality within 5 years of smoking cessation and decline thereafter. Further subgroup analyses showed interaction between smoking status and pulse rate (≥ 70 beats/min vs. < 70 beats/min) in relation to the risk of all-cause and non-cardiovascular mortality, with a higher risk in current versus never smokers in those participants with a pulse rate below 70 beats/min. CONCLUSIONS: Cigarette smoking in elderly Chinese confers significant risks of mortality, especially when recent former smoking is considered together with current smoking.

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.

Control status of ambulatory blood pressure and its relationship with arterial stiffness in the China nationwide registry of treated hypertensive patients: the REACTION-ABP study.

The control rate of ambulatory blood pressure (BP) is unclear in Chinese hypertensive patients, and whether it would be associated with the ambulatory arterial stiffness indices is also unknown. From June 2018 until December 2022, 4408 treated hypertensive patients (52.8% men, average age 58.2 years) from 77 hospitals in China were registered. Ambulatory BPs were measured with validated monitors and analyzed with a web-based standardized Shuoyun system ( www.shuoyun.com.cn ). The BP control rate was the highest in the office (65.7%), moderate in the daytime (45.0%), low in the morning (34.1%), and the lowest in the nighttime (27.6%, P < 0.001). Only 21.0% had their 24 h BP perfectly controlled. The stepwise regression analyses identified that the factors associated with an imperfect 24 h BP control included male sex, smoking and drinking habits, a higher body mass index, serum total cholesterol and triglycerides, and the use of several specific types of antihypertensive drugs. After adjustment for the above-mentioned factors, the 24 h pulse pressure (PP) and its components, the elastic and stiffening PPs, were all significantly associated with an uncontrolled office and ambulatory BP status with the standardized odds ratios ranging from 1.09 to 4.68 (P < 0.05). The ambulatory arterial stiffness index (AASI) was only associated with an uncontrolled nighttime and 24 h BP status. In conclusion, the control rates of 24 h ambulatory BP, especially that in the nighttime and morning time windows, were low in Chinese hypertensive patients, which might be associated with arterial stiffness in addition to other common risk factors.

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.

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.

Clinical First-Trimester Prediction Models for Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication that negatively impacts the health of both the mother and child. Early prediction of the risk of GDM may permit prompt and effective interventions. This systematic review and meta-analysis aimed to summarize the study characteristics, methodological quality, and model performance of first-trimester prediction model studies for GDM. METHODS: Five electronic databases, one clinical trial register, and gray literature were searched from the inception date to March 19, 2022. Studies developing or validating a first-trimester prediction model for GDM were included. Two reviewers independently extracted data according to an established checklist and assessed the risk of bias by the Prediction Model Risk of Bias Assessment Tool (PROBAST). We used a random-effects model to perform a quantitative meta-analysis of the predictive power of models that were externally validated at least three times. RESULTS: We identified 43 model development studies, six model development and external validation studies, and five external validation-only studies. Body mass index, maternal age, and fasting plasma glucose were the most commonly included predictors across all models. Multiple estimates of performance measures were available for eight of the models. Summary estimates range from 0.68 to 0.78 (I2 ranged from 0% to 97%). CONCLUSION: Most studies were assessed as having a high overall risk of bias. Only eight prediction models for GDM have been externally validated at least three times. Future research needs to focus on updating and externally validating existing models.

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.

Angiotensin-converting enzyme 2 in human plasma and lung tissue.

PURPOSE: We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery. MATERIALS AND METHODS: The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (n = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women). RESULTS: In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 vs. 0.98 ng/mL, p = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 vs. 53.9 a.u., p = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (p = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (p = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 vs. 0.98 ng/mL, p = 0.029 vs. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (p = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (p = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (p ≥ 0.20). CONCLUSION: ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.Plain language summary What is the context? • The primary physiological function of ACE2 is the degradation of angiotensin I and II to angiotensin 1-9 and 1-7, respectively. • ACE2 was found to behave as a mediator of the severe acute respiratory syndrome coronavirus (SARS) infection. • There is little research on ACE2 in humans, especially in the lung tissue. • In the present report, we investigated plasma ACE2 concentration and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue respectively in two study populations. What is new? • Our study investigated both circulating and tissue ACE2 in human subjects. The main findings were: • In men as well as women, plasma ACE2 concentration was higher in younger than older participants, whereas the mean intensity of ACE2 in the lung tissue increase with age increasing. • Compared with normotension, hypertensive patients had higher plasma ACE2 concentration but similar mean intensity of ACE2 in the lung tissue. • Neither plasma ACE2 concentration nor lung tissue ACE2 expression significantly differed between users of RAS inhibitors and other classes of antihypertensive drugs. What is the impact? • ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics, such as sex, age, and treated and untreated hypertension. • A major implication is that plasma ACE2 concentration might not be an appropriate surrogate for the ACE2 expression in the lung tissue, and hence not a good predictor of SARS-COV-2 infection or fatality.

Seasonal variation in the effect of antihypertensive treatment with the irbesartan/hydrochlorothiazide combination.

There is increasing awareness of seasonal variation in blood pressure (BP). In the present analysis, we investigated seasonal variation in the antihypertensive treatment effect of the irbesartan/hydrochlorothiazide combination in patients with stage 2 and 3 hypertension. The study participants were hypertensive patients enrolled in a 12-week therapeutic study. Antihypertensive treatment was initiated with irbesartan/hydrochlorothiazide 150/12.5 mg/day, with possible uptitration to 300/12.5 mg/day and 300/25 mg/day at 4 and 8 weeks of follow-up, respectively. The month of treatment commencement was classified as spring/summer (May to August) and autumn/winter (September to December). Of the 501 enrolled patients, 313 and 188 commenced antihypertensive treatment in spring/summer and autumn/winter, respectively. The mean changes in systolic/diastolic BP at 8 and 12 weeks of follow-up were greater in patients who commenced treatment in autumn/winter (-32.3/-16.5 and -34.2/-16.7 mmHg, respectively) than those who commenced treatment in spring/summer (-28.4/-13.9 and -27.1/-12.8 mmHg, respectively), with a between-season difference of 3.9 (95% confidence interval [CI], 1.4-6.4, P = 0.002)/2.6 (95% CI, 0.9-4.2, P = 0.002) mmHg and 7.0 (95% CI, 4.7-9.3, P < 0.0001)/3.9 (95% CI, 2.4-5.4, P < 0.0001) mmHg, respectively. Further subgroup analyses according to several baseline characteristics showed a greater between-season difference in the changes in systolic BP in patients aged ≥55 years than in those <55 years (n = 255, 12.6 mmHg vs. n = 246, 6.9 mmHg, P = 0.02), especially in patients who did not use antihypertensive medication at baseline (n = 94, 15.4 mmHg vs. n = 132, 5.4 mmHg, P = 0.006). In conclusion, there is indeed seasonality in the antihypertensive treatment effect, with a greater BP reduction in patients who commenced treatment in cold than warm seasons.

Serum triglycerides concentration in relation to total and cardiovascular mortality in an elderly Chinese population.

OBJECTIVE: To investigate serum triglycerides in relation to all-cause, cardiovascular, and non-cardiovascular mortality in an elderly Chinese population. METHODS: The study participants (n = 3565) were elderly (≥ 60 years) community dwellers living in a suburban town of Shanghai. Hypertriglyceridemia was defined as a serum triglycerides concentration ≥ 2.30 mmol/L (definite) and ≥ 1.70 mmol/L (borderline), respectively. RESULTS: The prevalence of definite and borderline hypertriglyceridemia at baseline was 7.5% and 29.5%, respectively. It was higher in women (n = 1982, 9.0% and 33.8%, respectively) than men (n = 1583, 6.2% and 27.9%, respectively), in obese and overweight participants (n = 1566, 10.5% and 36.4%, respectively) than normal weight participants (n = 1999, 5.6% and 27.1%, respectively), and in diabetic participants (n = 177, 11.9% and 39.0%, respectively) than non-diabetic participants (n = 3388, 7.5% and 30.8%, respectively). During a median of 7.9 years follow-up, all-cause, cardiovascular and non-cardiovascular deaths occurred in 529, 216 and 313 participants, respectively. In analyses according to the quintile distributions of serum triglycerides concentration, the sex- and age-standardized mortality rate was lowest in the middle quintile for all-cause, cardiovascular and non-cardiovascular mortality (18.6, 7.8 and 11.9 per 1000 person-years, respectively, versus 21.5, 10.5 and 12.7 per 1000 person-years, respectively, in the two lower quintiles and 21.7, 9.5 and 14.0 per 1000 person-years, respectively, in the two higher quintiles). The fully adjusted hazard ratios (95% CI) for the middle quintile versus the combined two lower with two higher quintiles were 0.85 (95% CI: 0.67-1.07, P = 0.17), 0.81 (95% CI: 0.54-1.19, P = 0.28) and 0.87 (95% CI: 0.64-1.17, P = 0.35) for all-cause, cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS: Our study showed high prevalence of hypertriglyceridemia, especially when defined as borderline and in obese and overweight participants, and mildly but non-significantly elevated risks of cardiovascular mortality relative to the middle level of serum triglycerides.

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.

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.