Treatment of Masked Hypertension with a Chinese Herbal Formula: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)-lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension. METHODS: Patients with an office BP of <140/90 mm Hg and daytime ambulatory BP of 135 to 150 mm Hg systolic or 85 to 95 mm Hg diastolic were randomly assigned 1:1 to the treatment of gastrodia-uncaria granules or placebo 5 to 10 g twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP. RESULTS: At baseline, office and daytime BP of the 251 participants (mean age, 50.4 years; 53.4% men; mean body mass index 24.5 kg/m2; and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes, and smoking, respectively) averaged 129/82 and 135/89 mm Hg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44/3.39 and 2.91/1.60 mm Hg in the gastrodia-uncaria granules and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mm Hg; P≤0.025) and 24-hour BP (2.33/1.49 mm Hg; P≤0.012), but not for the clinic and nighttime BPs (P≥0.162). The per-protocol analysis in 229 patients produced similar results. Only 1 adverse event (sleepiness during the day) was reported, and no serious adverse event occurred. CONCLUSIONS: BP-lowering treatment with Chinese traditional medicine gastrodia-uncaria granules is efficacious for patients with masked hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02156024.

Continuous positive airway pressure adherence and blood pressure lowering in patients with obstructive sleep apnoea syndrome and nocturnal hypertension.

PURPOSE: We investigated continuous positive airway pressure (CPAP) adherence and its association with the blood pressure (BP) and pulse rate changes in patients with obstructive sleep apnoea syndrome (OSAS) and hypertension. MATERIALS AND METHODS: In a single-blind trial, patients were randomly assigned to CPAP or sham CPAP treatment for 3 months. We performed clinic, ambulatory and home BP measurements at baseline and during follow-up. CPAP adherence was assessed as the CPAP frequency per week and time per night. Non-adherence was defined as a CPAP use for <5 days/week or <4 h/night. RESULTS: In the CPAP (n = 26) and sham CPAP groups (n = 21), the CPAP frequency was 5.5 and 4.8 days/week (p = 0.17), respectively, and the CPAP time was 5.0 and 4.1 h/night (p = 0.03), respectively. The corresponding prevalence of non-adherence was 46.2% and 66.7% (p = 0.16), respectively. The CPAP frequency but not time tended to be associated with the changes in BP and pulse rate at 3 months of follow-up, especially home systolic/diastolic BP in the CPAP group (3.2/1.3 mmHg greater reductions per 1 day increment, p ≤ 0.01). Adherent, compared with non-adherent patients, had greater reductions in BP or pulse rate at 3 months of follow-up. In the CPAP and sham CPAP groups combined, statistical significance was achieved for the adjusted between adherence and non-adherence differences in home systolic/diastolic BP (-5.0/-3.8 mmHg) and 24-h, daytime and night-time ambulatory pulse rate (-6.2, -7.8 and -4.4 beats/min, respectively, p ≤ 0.04). CONCLUSION: CPAP adherence was associated with the BP lowering and pulse rate slowing effects, especially the CPAP frequency.

Detection rate and treatment gap for atrial fibrillation identified through screening in community health centers in China (AF-CATCH): A prospective multicenter study.

BACKGROUND: Atrial fibrillation (AF) is underdiagnosed and especially undertreated in China. We aimed to investigate the prevalence of unknown and untreated AF in community residents (≥65 years old) and to determine whether an education intervention could improve oral anticoagulant (OAC) prescription. METHODS AND FINDINGS: We performed a single-time point screening for AF with a handheld single-lead electrocardiography (ECG) in Chinese residents (≥65 years old) in 5 community health centers in Shanghai from April to September 2017. Disease education and advice on referral to specialist clinics for OAC treatment were provided to all patients with actionable AF (newly detected or undertreated known AF) at the time of screening, and education was reinforced at 1 month. Follow-up occurred at 12 months. In total, 4,531 participants were screened (response rate 94.7%, mean age 71.6 ± 6.3 years, 44% male). Overall AF prevalence was 4.0% (known AF 3.5% [n = 161], new AF 0.5% [n = 22]). The 183 patients with AF were older (p < 0.001), taller (p = 0.02), and more likely to be male (p = 0.01), and they had a higher prevalence of cardiovascular disease than those without AF (p < 0.001). In total, 85% (155/183) of patients were recommended for OAC treatment by the established guidelines (CHA2DS2-VASc ≥ 2 for men; ≥ 3 for women). OAC prescription rate for known AF was 20% (28/138), and actionable AF constituted 2.8% of all those screened. At the 12-month follow-up in 103 patients (81% complete), despite disease education and advice on specialist referral, only 17 attended specialist clinics, and 4 were prescribed OAC. Of those not attending specialist clinics, 71 chose instead to attend community health centers or secondary hospital clinics, with none prescribed OAC, and 15 had no review. Of the 17 patients with new AF and a class 1 recommendation for OAC, only 3 attended a specialist clinic, and none were prescribed OAC. Of the 28 AF patients taking OAC at baseline, OAC was no longer taken in 4. Ischemic stroke (n = 2) or death (n = 3) occurred in 5/126 (4%), with none receiving OAC. As screening was performed at a single time point, some paroxysmal AF cases may have been missed; thus, the rate of new AF may be underestimated. CONCLUSIONS: We demonstrated a noticeable gap in AF detection and treatment in community-based elderly Chinese: actionable AF constituted a high proportion of those screened. Disease education and advice on specialist referral are insufficient to close the gap. Before more frequent or intensive screening for unknown AF could be recommended in China, greater efforts must be made to increase appropriate OAC therapy in known AF to prevent AF-related stroke.

A randomized controlled trial on ambulatory blood pressure lowering effect of CPAP in patients with obstructive sleep apnea and nocturnal hypertension.

Objective: In a randomised controlled trial, we investigated the blood pressure (BP) lowering effect of continuous positive airway pressure (CPAP) in patients with moderate-severe obstructive sleep apnoea syndrome (OSAS, an apnoea-hypopnoea index, AHI of 15 or higher) and nocturnal hypertension (night-time systolic/diastolic BP ≥120/70 mmHg).Methods: Sixty patients were randomly assigned to CPAP or sham CPAP, while maintaining their antihypertensive treatment. Ambulatory BP monitoring was performed at baseline (first run-in visit) and the end of follow-up. Clinic and home BP were measured at baseline and each of the monthly follow-up visits.Results: Of the 60 patients, 47 completed the 3-month study. CPAP (n = 26), compared with sham CPAP (n = 21), slightly and non-significantly reduced 24-h systolic/diastolic BP by -2.8/-2.5 mmHg (p ≥ 0.27), with a slightly greater between-group difference in the daytime (-4.0/-2.8 mmHg, p ≥ 0.29) than night-time (-0.2/-1.5 mmHg, p ≥ 0.50). The CPAP treatment did not significantly influence clinic or home BP during follow-up (p ≥ 0.27). Nonetheless, simple and partial correlation analyses showed that the ambulatory BP lowering effect was dependent on the daytime pulse rate at baseline (r ≥ 0.47, p ≤ 0.01). In patients with a daytime pulse rate greater than 85 beats/min, the mean changes in daytime systolic BP were significantly greater in the CPAP (n = 10) than sham CPAP group (n = 11), with a between-group mean difference of -10.1 mmHg (p = 0.048).Conclusions: The CPAP treatment did not show significant ambulatory BP lowering effect in patients with moderate-severe OSAS and nocturnal hypertension. However, it may be effective in lowering daytime BP in patients with a faster pulse rate.

Subtypes of masked hypertension and target organ damage in untreated outpatients.

Purpose: Masked hypertension (MHT) is characterised as an office normotension in the presence of out-of-office hypertension, and can be further categorised as isolated daytime (dMHT), night-time (nMHT) or day-night MHT (dnMHT) according to the time when hypertension is present. MHT is associated with adverse cardiovascular outcome. However, no previous studies contrasted these MHT subtypes in their associations with target organ damage (TOD).Materials and methods: Consecutive untreated patients referred for ambulatory blood pressure (BP) monitoring to our Hypertension Clinic were recruited. Office and ambulatory BPs were measured using the Omron 7051 and SpaceLabs 90217 monitors, respectively. The BP thresholds of daytime and night-time hypertension were of ≥135/85 mmHg and ≥120/70 mmHg, respectively. We performed various TOD measurements, including carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), left ventricular mass index (LVMI) and E/E', estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR).Results: The 1808 participants (mean age, 51 years; women, 52%) included 672 (37.2%) MHT subjects, among whom 123 (18.3%) had dMHT, 78 (11.6%) nMHT, and 471 (70.1%) dnMHT. In all participants as well as patients with office normotension (n = 1222), ambulatory daytime and night-time BPs were similarly associated with all TOD measurements (p ≥ 0.20) after multivariate adjustment. Compared to normotensive subjects (p < 0.05), patients with dMHT had faster cfPWV (7.81 vs. 7.58 m/s) and thicker cIMT (637.6 vs. 610.4 µm), patients with nMHT had thicker cIMT (641.8 vs. 610.4 µm) and increased UACR (0.79 vs. 0.59 mg/mmol), and patients with dnMHT had all worse TOD measures mentioned-above plus elevated eGFR (120.7 vs. 116.8 ml/min/1.73m2).Conclusion: MHT was associated with TOD irrespective of subtype, although TOD varied slightly across these subtypes. The study highlights the importance of controlling both daytime and night-time BP in hypertensive patients.

Short-term reproducibility of the 24-h ambulatory monitoring of brachial and central hemodynamics in untreated Chinese.

Objective: Advanced technology allows non-invasive monitoring of the 24-h brachial and central hemodynamics simultaneously. However, related reproducibility data was limited in White patients. We therefore explored if the novel measurements would be reproducible in Chinese. Methods: From February 2017 to January 2018, 152 untreated patients who were suspected of hypertension and referred for ambulatory blood pressure (BP) monitoring were recruited. Ambulatory BP monitoring was repeated within one month (median, 12.5 days) using the Mobil-O-Graph monitors (IEM, Germany). Reproducibility was assessed as the intra-class correlation coefficient (ICC), coefficient of variation (CV), and repeatability coefficient (RC). Results: The 152 participants (average age, 58.6 years) included 54 men and 98 women. The first and second means of the ambulatory brachial and central BPs, pulse wave velocity (PWV), augmentation pressure, augmentation index (AIx) and AIx at a heart rate of 75 beats per minute (AIx@75) were all similar (p ≥ 0.065), except that the repeated daytime and 24-h brachial and central systolic BPs and pulse pressure slightly differed by approximately 1-2 mmHg (p ≤ 0.011). ICC ranged from 0.70 to 0.94 for all ambulatory BPs and ≥0.91 for the arterial measurements. CV was in the range from 5.0% to 10.3% for all BPs and PWV measurements, and from 15.5% to 22.3% for AIx and AIx@75. RC expressed as percentages of maximal variation was <15% for the PWVs and ranged from 25.5% to 54.7% for BPs, AIx and AIx@75. Conclusions: The 24-h ambulatory brachial and central BPs and arterial measurements were reproducible within a short time period in Chinese, and could therefore be used in clinical practice and research settings.

Association of pulse wave velocity with single nucleotide polymorphisms related to parathyroid hormone.

OBJECTIVE: Carotid-femoral pulse wave velocity (cfPWV) was associated with serum parathyroid hormone (PTH) in untreated Chinese. We investigated in the same cohort whether cfPWV, brachial-ankle (baPWV) and heart-brachial (hbPWV) pulse wave velocity (PWV) were associated with rs6127099 (CYP24A1) and rs4074995 (RGS14). A previously published genome-wide association study demonstrated that each additional copy of the T (rs6127099) or G (rs4074995) allele was associated with a 7% or 3% higher serum PTH, respectively. METHODS: In 1601 untreated Chinese patients (mean age, 51.0 years; 51.9% women), we measured cfPWV by tonometry (SphygmoCor) and baPWV and hbPWV by combined oscillometry and plethysmography (VP-2000 PWV/ABI analyser), serum PTH by an immunoassay, and genotypes by the SNapShot method. RESULTS: cfPWV, baPWV and hbPWV averaged 7.9, 14.6 and 5.5 m/s and serum PTH 65.7 pg/mL. Genotype frequencies were in Hardy-Weinberg equilibrium, amounting to 41.7% (AA), 44.9% (AT) and 13.4% (TT) for rs6127099 and to 70.7% (GG), 26.9% (GA) and 2.3% (AA) for rs4074995. With adjustments applied for sex, age, body mass index, heart rate and season, hbPWV was 0.05 m/s (p = .042) lower with each additional copy of the minor allele (T) of rs6127099. In similarly adjusted analyses of 157 normotensive participants younger than 50 years, cfPWV was 0.32 m/s (p = .004) higher per additional copy of the T allele. Sensitivity analyses additionally accounting for the total-to-HDL serum cholesterol ratio, plasma glucose, glomerular filtration rate and 24 h systolic blood pressure were consistent. No other association of PWV with the genetic variants reached significance. CONCLUSIONS: With an increasing number of rs6127099 T alleles, arterial stiffness, as exemplified by PWV, was lower in all participants in a muscular artery (hbPWV), but higher in young normotensive participants in an elastic artery (cfPWV).

Cardiovascular risks associated with diastolic blood pressure and isolated diastolic hypertension.

UNLABELLED: Hypertension is a major reversible risk factor for cardiovascular complications. According to recent guidelines, hypertension can be subdivided into isolated diastolic, isolated systolic, and systolic and diastolic mixed hypertension using proposed thresholds of various blood pressure components. In the present article, we reviewed the association of cardiovascular outcomes with diastolic blood pressure versus systolic blood pressure and with isolated diastolic hypertension versus systolic and mixed hypertension in observational prospective cohort studies and large-scale individual data-based meta-analysis. Blood pressure was measured either in the clinic or at home or under ambulatory conditions for 24 h in cohort studies. To illustrate the treatment effect of diastolic blood pressure lowering, we also reviewed randomized placebo-controlled outcome trials in diastolic hypertension. CONCLUSIONS: The risks conferred by diastolic and systolic blood pressure, irrespective of the methods of blood pressure measurement, are age-dependent. Diastolic blood pressure and isolated diastolic hypertension drive coronary risk in younger subjects, whereas systolic blood pressure is the predominant risk indicator in older people. Reversibility of the risk by diastolic BP lowering treatment in randomized trials confirms that diastolic hypertension is a risk factor that must be treated.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.