Long-term effects of blood pressure 130-139/80-89 mmHg on all-cause and cardiovascular mortality among Chinese adults with different glucose metabolism.

BACKGROUND: This study aimed to investigate the risks of all-cause and cardiovascular mortality associated with blood pressure (BP) levels of 130-139/80-89 mmHg in Chinese adults with different glucose metabolism, during a long-term follow-up of over 20 years. METHODS: A prospective population-based cohort of 2,132 adults in Shanghai was established in 2002 and followed for 21 years. The association between BP categories and mortality was assessed, and the risk was further analyzed using multiple Cox regression analysis by combining BP and blood glucose categories. RESULTS: The final analysis included 2,004 participants, with 397 all-cause and 166 cardiovascular mortality. The incidence of all-cause and cardiovascular mortality per 1,000 person-years for different BP categories were as follows: BP < 130/80 mmHg (4.5 and 1.3), 130-139/80-89 mmHg (7.7 and 2.9), and ≥ 140/90 mmHg or treated groups (19.9 and 8.7), respectively. After adjusting for age, sex, and other factors, BP ≥ 140/90 mmHg was significantly associated with a higher risk of mortality across different blood glucose categories. However, using BP < 130/80 mmHg and normoglycemia as the reference, a BP of 130-139/80-89 mmHg was significantly associated with higher risks of all-cause (hazard ratio 3.30 [95% confidence interval 1.48-7.38], P < 0.01) and cardiovascular mortality (9.60 [1.93-47.7], P < 0.01) in diabetes, but not in those with normoglycemia or prediabetes. CONCLUSIONS: BP of 130-139/80-89 mmHg may lead to a significantly higher risk of all-cause and cardiovascular mortality in Chinese adults with diabetes, but not in those with normoglycemia or prediabetes. This suggests that the targeted BP for people with diabetes should be < 130-139/80-89 mmHg.

Anxiety prevalence and its association with physical activity in patients with non-communicable diseases during COVID-19 lockdown: a cross-sectional study in Shanghai, China.

BACKGROUND: Quarantine due to the COVID-19 pandemic may have created great psychological stress among vulnerable populations. We aimed to investigate the prevalence of anxiety and explore the association between physical activities (PA) and anxiety risk in people with non-communicable diseases during the period of COVID-19 lockdown. METHODS: We conducted a cross-sectional telephone survey from February 25 to April 20, 2020, the period of COVID-19 lockdown in Shanghai. Up to 8000 patients with type 2 diabetes and/or hypertension were selected using multi-stage cluster random sampling. PA level was measured based on the International Physical Activity Questionnaire using Metabolic Equivalent for Task scores, while symptoms of anxiety were assessed by the 7-item Generalized Anxiety Disorder scale. Multiple logistic regression analyses were performed to evaluate the associations of type and level of PA with the risk of anxiety. RESULTS: Of a total 4877 eligible patients, 2602 (53.4%) reported with anxiety, and 2463 (50.5%), 123 (2.5%) and 16 (0.3%) reported with mild, moderate, and severe anxiety. The prevalence of anxiety was higher in the females, the elders, non-smokers, non-drinkers, and patients with diabetes, and the associations of anxiety with sex, age, smoking, drinking and diagnosis of diabetes were significant. A significant negative association was observed for housework activities (OR 0.53, 95%CI: [0.45, 0.63], p < 0.001) and trip activities (OR 0.55, 95%CI: [0.48, 0.63], p < 0.001) with anxiety, but no significant was found for exercise activities (OR 1.06, 95%CI: [0.94, 1.20], p = 0.321). Compared with patients with a low PA level, those with a moderate (OR 0.53, 95%CI: [0.44, 0.64], p < 0.001) or a high PA level (OR 0.51, 95%CI: [0.43, 0.51], p < 0.001) had a lower prevalence of anxiety. CONCLUSION: This study demonstrates a higher prevalence of anxiety in patients with hypertension, diabetes, or both during the COVID-19 lockdown. The negative associations of housework and trip activities with anxiety highlight the potential benefit of PA among patients with non-communicable diseases.

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.

Prognostic significance of visit-to-visit variability, and maximum and minimum LDL cholesterol in diabetes mellitus.

BACKGROUND: Current guidelines for dyslipidemia management recommend that the LDL-C goal be lower than 70 mg/dL. The present study investigated the prognostic significance of visit-to-visit variability in LDL-C, and minimum and maximum LDL-C during follow-up in diabetes mellitus. METHODS: The risk of outcomes in relation to visit-to-visit LDL-C variability was investigated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. LDL-C variability indices were coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). Multivariable Cox proportional hazards models were employed to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with the placebo group (n=2667), the fenofibrate therapy group (n=2673) had a significantly (P<0.01) lower mean plasma triglyceride (152.5 vs. 178.6 mg/dL), and total cholesterol (158.3 vs.162.9 mg/dL) but a similar mean LDL-C during follow-up (88.2 vs. 88.6 mg/dL, P>0.05). All three variability indices were associated with primary outcome, total mortality and cardiovascular mortality both in the total population and in the fenofibrate therapy group but only with primary outcome in the placebo group. The minimum LDL-C but not the maximum during follow-up was significantly associated with various outcomes in the total population, fenofibrate therapy and placebo group. The minimum LDL-C during follow-up ≥70 mg/dL was associated with an increased risk for various outcomes. CONCLUSIONS: Visit-to-visit variability in LDL-C was a strong predictor of outcomes, independent of mean LDL-C. Patients with LDL-C controlled to less than 70 mg/dL during follow-up might have a benign prognosis. ClinicalTrials.gov number: NCT00000620.

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.

Alcohol consumption in relation to cardiovascular and non-cardiovascular mortality in an elderly male Chinese population.

BACKGROUND: We investigated the association of alcohol consumption with cardiovascular and non-cardiovascular mortality in elderly Chinese men. METHODS: Our participants were recruited from residents living in a suburban town of Shanghai (≥60 years of age, n = 1702). Alcohol intake was classified as non-drinkers, past drinkers (stopped drinking for ≥12 months), and current light-to-moderate (1 to 299 g/week) and heavy drinkers (≥300 g/week). Alcoholic beverages were classified as beer/wine, rice aperitif and liquor/mix drinking. RESULTS: During 5.9 years (median) of follow-up, all-cause, cardiovascular and non-cardiovascular deaths occurred in 211, 98 and 113 participants, respectively. The corresponding incidence rates were 23.6/1000, 10.9/1000 and 12.6/1000 person-years, respectively. Both before and after adjustment for confounding factors, compared with non-drinkers (n = 843), past drinkers (n = 241), but not the current light-to-moderate (n = 241) or heavy drinkers (n = 377), had a higher risk of all-cause (adjusted hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.35-2.68, P = 0.0003) and non-cardiovascular mortality (HR 2.46, 95% CI 1.55-3.91, P = 0.0001). Similar trends were observed for cardiovascular mortality (HR 1.44, 95% CI 0.85-2.44, P = 0.18). In similar unadjusted and adjusted analyses, compared with the current beer/wine drinkers (n = 203), liquor/mix drinkers (n = 142), but not aperitif drinkers (n = 273), had a significantly higher risk of all-cause (HR 3.07, 95% CI 1.39-6.79, P = 0.006), and cardiovascular mortality (HR 10.49, 95% CI 2.00-55.22, P = 0.006). Similar trends were observed for non-cardiovascular mortality (HR 1.94, 95% CI 0.73-5.16, P = 0.18). CONCLUSIONS: Our study showed risks of mortality associated with past drinking and liquor drinking in the elderly Chinese men.

Serum uric acid change in relation to antihypertensive therapy with the dihydropyridine calcium channel blockers.

PURPOSE: We investigated serum uric acid changes in relation to the achieved clinic and ambulatory blood pressure after 8 weeks of antihypertensive therapy with two dihydropyridine calcium channel blockers. MATERIALS AND METHODS: The study participants were patients with clinic and ambulatory hypertension, enrolled in a randomised controlled trial that compared amlodipine (5-10 mg, n = 215) and nifedipine gastrointestinal therapeutic system (GITS, 30-60 mg, n = 203). Hyperuricaemia was defined as a serum uric acid concentration of ≥420 µmol/L in men and ≥360 µmol/L in women. Analysis of covariance and multiple regression analyses were performed to study the associations between serum uric acid changes and the achieved clinic and ambulatory blood pressure during follow-up. RESULTS: At baseline, 67 (16.0%) of the 418 patients had hyperuricaemia. Antihypertensive treatment reduced clinic and 24-h daytime and night-time systolic/diastolic blood pressure by a mean (±standard error [SE]) change of -17.4 ± 0.6/-8.6 ± 0.4 mm Hg and -13.7 ± 0.5/-8.3 ± 0.3 mm Hg, -13.8 ± 0.6/-8.4 ± 0.4 mm Hg, and -12.7 ± 0.7/-8.0 ± 0.4 mm Hg, respectively. Antihypertensive treatment reduced serum uric acid by a mean (±SE) change of -9.3 ± 2.8 µmol/L. The serum uric acid changes differed according to the achieved clinic and ambulatory blood pressure, and were statistically significant (mean ± SE -20.6 ± 6.6 to -10.7 ± 2.9 µmol/L, p ≤ 0.04) at the systolic/diastolic ranges of 130-139/≥90 mm Hg in clinic pressure, and <130/75-84 mm Hg, <145/80-84 mm Hg and <120/65-69 mm Hg in 24-h, daytime and night-time ambulatory pressure. CONCLUSION: Our study showed that antihypertensive therapy with a dihydropyridine calcium channel blocker was associated with reduced serum uric acid, especially when 24-h ambulatory systolic blood pressure was controlled.

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.

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.

May Measurement Month 2017: an analysis of blood pressure screening results in China-East Asia.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. In China, several hypertension screening programmes are undertaken in the elderly in the community and in youths at university entrance and graduation. However, most people, especially the middle-aged working population, do not often have their BP measured. The current awareness (46.9%), treatment (40.7%), and control rates (15.3%) of hypertension remain low, while the proportion of screenees with hypertension is high in adult Chinese (23.2%). An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. About 125 236 individuals were screened. After multiple imputation, with 124 623 as denominator, 32 089 (25.7%) had hypertension. Of the 103 981 individuals not on antihypertensive medication, 11 447 (11.0%) were hypertensive. Of the 20 547 individuals on antihypertensive medication, 7392 (36.0%) had uncontrolled BP (≥140/90 mmHg). An opportunistic screening may effectively identify those with high BP regardless of the use of antihypertensive medication and shows similar information on BP as a survey in a randomly selected population sample.

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).

PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population.

BACKGROUND: Platelet Endothelial Aggregation Receptor 1 (PEAR1), a membrane protein highly expressed in platelets and endothelial cells, plays a role in platelet contact-induced activation, sustained platelet aggregation and endothelial function. Previous reports implicate PEAR1 rs12041331 as a variant influencing risk in patients with coronary heart disease. We investigated whether genetic variation in PEAR1 predicts cardiovascular outcome in a white population. METHODS: In 1938 participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes (51.3% women; mean age 43.6 years), we genotyped 9 tagging SNPs in PEAR1, measured baseline cardiovascular risk factors, and recorded Cardiovascular disease incidence. For SNPs, we contrasted cardiovascular disease incidence of minor-allele heterozygotes and homozygotes (variant) vs. major-allele homozygotes (reference) and for haplotypes carriers vs. non-carriers. In adjusted analyses, we accounted for family clusters and baseline covariables, including sex, age, body mass index, mean arterial pressure, the total-to-HDL cholesterol ratio, smoking and drinking, antihypertensive drug treatment, and history of cardiovascular disease and diabetes mellitus. RESULTS: Over a median follow-up of 15.3 years, 238 died and 181 experienced a major cardiovascular endpoint. The multivariable-adjusted hazard ratios of eight PEAR1 SNPs, including rs12566888, ranged from 0.87 to 1.07 (P ≥0.35) and from 0.78 to 1.30 (P ≥0.15), respectively. The hazard ratios of three haplotypes with frequency ≥10% ranged from 0.93 to 1.11 (P ≥0.49) for mortality and from 0.84 to 1.03 (P ≥0.29) for a cardiovascular complications. These results were not influenced by intake of antiplatelet drugs, nonsteroidal anti-inflammatory drugs, or both (P-values for interaction ≥ 0.056). CONCLUSIONS: In a White population, we could not replicate previous reports from experimental studies or obtained in patients suggesting that PEAR1 might be a susceptibility gene for cardiovascular complications.

The prevalence, incidence, management and risks of atrial fibrillation in an elderly Chinese population: a prospective study.

BACKGROUND: There is limited information on prevalent and incident atrial fibrillation in Chinese. We aimed to investigate the prevalence, incidence, management and risks of atrial fibrillation in an elderly Chinese population. METHODS: In a population--based prospective study in elderly (≥ 60 years) Chinese, we performed cardiovascular health examinations including a 12-lead electrocardiogram at baseline in 3,922 participants and biennially during follow-up in 2,017 participants. We collected information on vital status during the whole follow-up period. RESULTS: The baseline prevalence of atrial fibrillation was 2.0 % (n = 34) in 1718 men and 1.6 % (n = 36) in 2204 women. During a median 3.8 years of follow-up, the incidence rate of atrial fibrillation (n = 34) was 4.9 per 1000 person-years (95 % confidence interval [CI], 3.4-6.9). In univariate analysis, both the prevalence and incidence of atrial fibrillation were higher with age advancing (P < 0.0001) and in the presence of coronary heart disease (P ≤ 0.02). Of the 104 prevalent and incident cases of atrial fibrillation, only 1 (1.0 %) received anticoagulant therapy (warfarin). These patients with atrial fibrillation, compared with those with sinus rhythm, had significantly higher risks of all-cause (n = 261, hazard ratio [HR] 1.87, 95 % CI, 1.09-3.20, P = 0.02), cardiovascular (n = 136, HR 3.78, 95 % CI 2.17-6.58, P < 0.0001) and stroke mortality (n = 44, HR 6.31, 95 % CI 2.81-14.19, P = 0.0003). CONCLUSIONS: Atrial fibrillation was relatively frequent in elderly Chinese, poorly managed and associated with higher risks of mortality.

Blood pressure and urinary sodium excretion in relation to 16 genetic polymorphisms in the natriuretic peptide system in Chinese.

We systematically investigated the association between single nucleotide polymorphisms (SNPs) in the natriuretic peptide system (NPPA, NPPB, NPPC, NPRA, NPRC, and Corin genes) and blood pressure in a Chinese population. The study population was recruited from a mountainous area 500 km south of Shanghai from 2003 to 2009. Using the ABI SNapShot method, we first genotyped 951 subjects enrolled in 2005 for 16 SNPs and then the remaining 1355 subjects as validation for 5 SNPs selected from the primary study. Overall, the association of the studied genetic polymorphisms with blood pressure and urinary excretion of cations was weak or non-significant. However, in the primary study, there was significant (Pint = 0.003) interaction between the rs198358 polymorphism and age in relation to diastolic blood pressure. After adjustment for covariates, diastolic blood pressure was significantly higher in the G allele carriers than AA homozygotes in 176 subjects aged 60 years or older (77.8 ± 1.72 vs 73.9 ± 1.54 mmHg, P = 0.001). In the primary combined with validation studies, this interaction remained statistically significant (Pint = 0.02). The odds ratio of hypertension for carrying the G allele versus AA homozygotes was 1.25 (95% CI: 1.03-1.52; P = 0.03) in all subjects, and 0.85 (0.51-1.41; P = 0.53), 1.30 (0.98-1.73; P = 0.06), and 1.45 (0.95-2.22; P = 0.08) in the subjects younger than 40 years, 40-59 years, and 60 years or older, respectively. Some of the genetic polymorphisms in the natriuretic peptide system might be associated with blood pressure. However, not only the size, but also the direction of the association may change with age.

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.

Association Between Age at Diabetes Diagnosis and Subsequent Incidence of Cancer: A Longitudinal Population-Based Cohort.

OBJECTIVE: Diabetes presenting at a younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes mellitus (T2DM) diagnosis with subsequent cancer incidence in a large Chinese population. RESEARCH DESIGN AND METHODS: The prospective population-based longitudinal cohort included 428,568 newly diagnosed T2DM patients from 2011 to 2018. Participants were divided into six groups according to their age at diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years. The incidence of overall and 14 site-specific cancers was compared with the Shanghai general population including 100,649,346 person-years. RESULTS: A total of 18,853 and 582,643 overall cancer cases were recorded in the T2DM cohort and the general population. The age-standardized rate of overall cancer in T2DM patients was 501 (95% CI: 491, 511) per 100,000 person-years, and the standardized incidence ratio (SIR) was 1.10 (1.09, 1.12). Younger age at T2DM diagnosis was associated with higher incidence of overall and site-specific cancers. SIRs for overall cancer with T2DM diagnosis at ages 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years were 1.48 (1.41, 1.54), 1.30 (1.25, 1.35), 1.19 (1.15, 1.23), 1.16 (1.12, 1.20), 1.06 (1.02, 1.10), and 0.86 (0.84, 0.89), respectively. Similar trends were observed for site-specific cancers, including respiratory, colorectum, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancer and lymphoma among both males and females. CONCLUSIONS: Our findings highlight the necessity of stratifying management for T2DM according to age of diagnosis. As with a range of vascular outcomes, age-standardized cancer risks are greater in earlier compared with later onset T2DM.

Albuminuria in relation to the single and combined effects of systolic and diastolic blood pressure in Chinese.

We investigated the single and combined effects of systolic (SBP) and diastolic blood pressure (DBP) on albuminuria in Chinese. We measured blood pressure (BP), anthropometry and urinary excretions of albumin and creatinine, and defined albuminuria as a urinary albumin-to-creatinine ratio of at least 17 and 25 mg/g in men and women, respectively. The 1068 participants (mean age 56.3 years) included 407 (38.5%) men and 410 (38.4%) hypertensive patients. A J-shaped relationship between the risk of albuminuria and BP was observed for both SBP (mean ± SD, 126.1 ± 18.9 mmHg) and DBP (77.1 ± 9.4 mmHg) with nadir levels of 110 mmHg and 70 mmHg, respectively. The risk of albuminuria was significantly (p ≤ 0.01) associated with DBP in the subjects with a SBP of at least 130 mmHg and with SBP in subjects with a DBP of at least 80 mmHg, and inversely and significantly (p = 0.04) associated with SBP in subjects with a DBP below 70 mmHg. In conclusion, as far as albuminuria is concerned, there is indeed a J-shaped phenomenon. However, it has a nadir level far below the currently recommended target BP of 140/90 or 130/80 mmHg.

Diastolic and systolic blood pressure time in target range as a cardiovascular risk marker in patients with type 2 diabetes: A post hoc analysis of ACCORD BP trial.

AIMS: We investigated the associations between time in target range (TTR) of blood pressure (BP) and cardiovascular outcomes in patients with diabetes. METHODS: 4651 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) BP trial were included in the present study. The diastolic BP target range was defined as 70 to 80 mm Hg, and the systolic as 120 to 140 mm Hg and 110 to 130 mm Hg for the standard and intensive therapy, respectively. RESULTS: After adjusting for covariates, 1-SD increase of diastolic TTR was significantly associated with lower risks of primary outcome (HR 0.82, 95% CI: 0.74-0.91, P < 0.001; HR 0.86, 95% CI: 0.77-0.95, P = 0.0044, as well as nonfatal myocardial infarction (HR 0.79, 95% CI: 0.69-0.91, P < 0.001). Meanwhile, systolic TTR was significantly associated with various cardiovascular outcomes (P ≤ 0.016) in fully-adjusted models. The diastolic TTR sustained significance in myocardial infarction when systolic blood pressure average was higher than 120 mm Hg. CONCLUSIONS: In patients with diabetes, TTR of diastolic and systolic BP was independently associated with lower risks of major outcomes. The diastolic BP within the optimal target range was considerably important for reducing the risk of myocardial infarction, even when systolic BP was under stable control.

Cumulative HbA1c exposure as a CVD risk in patients with type 2 diabetes: A post hoc analysis of ACCORD trial.

AIMS: The study aimed to investigate the relationship between cumulative HbA1c exposure and cardiovascular events in patients with type 2 diabetes (T2D). METHODS: This study included 9307 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Cumulative HbA1c exposure was calculated as the area under the curve during exposure time. RESULTS: After adjusting for covariates, a 1-SD increase in cumulative HbA1c exposure was significantly associated with a higher risk of the primary outcome (HR 1.32, 95 % CI: 1.22-1.43, P < 0.001), all-cause mortality (HR 1.33, 95 % CI: 1.21-1.46, P < 0.001), and cardiovascular death (HR 1.45, 95 % CI: 1.27-1.67, P < 0.001). These associations were independent of baseline HbA1c and the first HbA1c level after enrollment. Cross-tabulation analysis showed that participants in the intensive-therapy group with high baseline HbA1c and cumulative HbA1c exposure had a significantly higher risk of primary outcome, all-cause mortality and cardiovascular death. CONCLUSIONS: Higher cumulative HbA1c exposure was significantly associated with an increased risk of the primary outcome, all-cause mortality and cardiovascular death among T2D patients. Patients with T2D should strive for stable glycemic control to reduce their risk of cardiovascular events, and that those with high baseline HbA1c may require more intensive therapy to achieve this goal.