Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

Association of serum resistin with cystatin C and urinary albumin-to-creatinine ratio in elderly Chinese men with essential hypertension.

PURPOSE OF THE STUDY: Resistin, a recently discovered proinflammatory cytokine, has been strongly linked to kidney dysfunction. The aim of this study was to determine the relationship of serum resistin with serum cystatin C (sCysC) and albuminuria, two sensitive endogenous markers of renal function, in elderly male patients with essential hypertension (EH). STUDY DESIGN: This was a cross-sectional study enrolling 296 Chinese men (age ≥60 years, mean age 81.42 years) diagnosed with EH between January 2008 and May 2011. Renal function was assessed by measurement of sCysC levels and albuminuria (calculated as the urine albumin-to-creatinine ratio (uACR)). Serum resistin and selected metabolic and cardiovascular markers were determined by serological testing. Relationships between serum resistin levels and sCysC levels and uACR were analysed using multiple regression analysis. RESULTS: Multiple linear regression analyses revealed that the serum resistin level was positively associated with the sCysC level and uACR (ß(uACR)=0.132, p(uACR)=0.002; ß(sCysC)=0.015, p(sCysC)=0.008). CONCLUSIONS: Our findings demonstrated that a raised serum resistin level is a potential indicator of renal dysfunction in elderly patients with EH. Resistin may be explored as a potential biomarker in addition to sCysC and uACR to provide a more accurate diagnosis of renal damage in elderly men with EH.

Serum cystatin C and indices of lung function in elderly Chinese men with chronic obstructive pulmonary disease.

OBJECTIVE: The aim of this cross-sectional case-control study was to determine the relationship between serum cystatin C (sCysC) levels and lung function in elderly male patients with chronic obstructive pulmonary disease (COPD). METHODS: This study included 251 Chinese men (age ≥ 65 years) who were divided into COPD (n = 129) and non-COPD (n = 122) groups. Participants underwent lung function and laboratory testing, including measurement of sCysC levels. Relationships between sCysC concentration and indices of lung function were assessed by multiple regression analysis. RESULTS: Participants in the COPD group displayed higher sCysC concentrations (P = 0.041) and lower lung function (P < 0.001) compared to participants in the non-COPD group. Multiple linear regression analyses revealed that the reciprocal of the sCysC concentration (1/sCysC) was positively associated with the predicted forced expiratory volume in 1 s in all subjects (ß = 0.156, P = 0.009). The findings indicate that high sCysC levels were directly associated with decreased lung function in elderly Chinese men with COPD. CONCLUSIONS: High sCysC concentration may be a potential indicator of impaired lung function, and its application may improve the diagnosis and assessment of COPD severity in elderly male patients.

Frequency, risk factors, prognosis, and genetic polymorphism of the cyclooxygenase-1 gene for aspirin resistance in elderly Chinese patients with cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is an important cause of mortality in elderly patients worldwide. Aspirin resistance has been well reported in CVD. OBJECTIVE: The frequency, risk factors, prognosis, and genetic polymorphism of the cyclooxygenase-1 (COX-1) gene for aspirin resistance have not been reported in elderly patients with CVD. We therefore undertook this study to evaluate these associations among elderly Chinese patients with CVD. METHODS: Four hundred thirty-one elderly Chinese patients with CVD receiving daily aspirin therapy (≥75 mg) over 1 month were enrolled. Platelet aggregation was measured by light transmission aggregometry (LTA) and thromboelastography platelet mapping assay (TEG) using arachidonic acid (AA) as a stimulus. The median follow-up was 1.8 years. RESULTS: After the median follow-up, aspirin-resistant patients were at an increased risk of the composite endpoint compared to nonresistant patients by LTAAA + TEGAA (23.7 vs. 9.2%, p = 0.025). Additionally, Cox proportional hazards regression modeling demonstrated that aspirin resistance and cerebrovascular disease were associated with major adverse long-term outcomes (HR for aspirin resistance = 2.31, 95% CI 1.11-4.81, p = 0.026). The variant G-allele of COX-1 rs1330344 (-1676 A/G) significantly increased the risk of aspirin resistance defined by LTAAA + TEGAA (OR = 1.82, 95% CI 1.13- 2.92, p = 0.01). CONCLUSIONS: Aspirin resistance, evaluated by LTAAA + TEGAA, is associated with an increased risk of adverse clinical events in elderly Chinese patients with CVD. The variant G-allele of COX-1 rs1330344 is significantly associated with aspirin resistance defined by LTAAA + TEGAA.

Correlation between sex hormone levels and obesity in the elderly male.

OBJECTIVE: To investigate the levels of sex hormones and androgen receptor (AR) in elderly male patients and to explore a possible correlation with obesity. METHODS: The cross-sectional study included 314 Elderly males (age ≥ 65 year). Of these subjects, 104 were healthy (age range 65-92 year; mean 71.38 ± 5.154 year), 74 were obese (65-87 year; 71.32 ± 4.74 year), and 111 were overweight (65-85 year; 71.43 ± 5.03 year). The following parameters were measured: total testosterone (TT), free testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), estradiol (E2), luteinizing hormone, follicle-stimulating hormone and AR. RESULTS: (i) The levels of TT and SHBG in the obesity group were significantly lower than those in non-obese subjects. (ii) Body mass index (BMI) negatively correlated with TT and SHBG. (iii) Multiple regression analysis revealed that TT (ß: -0.230; p = 0.045) and SHBG (ß: -0.163; p = 0.02) were statistically correlated with BMI. CONCLUSION: Testosterone levels in the obese population were significantly lower than in the non-obese population and there is a significant association between testosterone levels and the extent of obesity.

The prevalence, risk factors and prognosis of aspirin resistance in elderly male patients with cardiovascular disease.

AIM: Aspirin resistance is recognized in different population. However, the prevalence and clinical events of aspirin resistance in elderly male patients with cardiovascular disease (CVD) have not been reported. METHODS: We enrolled 304 elderly male patients with CVD receiving daily aspirin therapy (≥ 75 mg) more than 1 month. Platelet aggregation was measured by light transmission aggregometry (LTA) and thrombelastography platelet mapping assay (TEG). The median follow-up time was 1.8 years. The primary outcome was the composite of death, myocardial infarction, unstable angina, stroke and transient ischemic attack. RESULTS: By LTA, 25 (8.2%) of elderly patients were aspirin resistant and 106 (34.9%) patients were semiresponders. According to TEG, 62 patients (20.4%) were found to be resistant to aspirin therapy. Of the 62 patients with aspirin resistance by TEG, 21 patients were aspirin resistant by LTA. Twenty-two of the 106 semiresponders by LTA were aspirin resistant by TEG. Patients with aspirin resistance or aspirin semiresponders were at increased risk of the composite outcome compared with aspirin-sensitive patients by LTA (18.3% vs 9.8%, Hazard ratio (HR) = 1.864, 95% confidence interval (CI): 1.046-3.324 p = 0.039). However, aspirin resistance was not associated with an increased risk of clinical vascular events compared to aspirin-sensitive patients by TEG (17.7% vs 10.9%, p = 0.452). In addition, Cox proportional hazard regression modeling demonstrated that aspirin resistance or semiresponders (HR = 3.050, 95% CI: 1.464-6.354, p = 0.003) and diabetes (HR = 2.055, 95% CI: 1.060-3.981, p = 0.033) were associated with major adverse long-term outcomes. CONCLUSIONS: Aspirin resistance or semiresponders, defined by LTA, are associated with an increased risk of adverse clinical events in elderly male patients with CVD.

Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study.

BACKGROUND: Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed. METHODS: A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety. DISCUSSION: Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling. TRIAL REGISTRATION: ClinicalTrials.gov NCT04406129 . Registered on May 28, 2020.

Correlation of sex hormone and androgen receptor with diabetes mellitus in elderly men.

AIM: To investigate sex hormone and androgen receptor (AR) levels and to evaluate their relationship with diabetes mellitus (DM) in senile men. METHODS: The cross-sectional study included 492 elderly men comprising 104 healthy subjects (mean age 71.4 ± 5.2 years), 259 subjects without DM (71.5 ± 5.0 years) and 129 DM patients (73.0 ± 6.3 years). Plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG), estradiol (E(2)), luteinising hormone) and follicle-stimulating hormone (FSH) were determined. AR-positive cells were measured by flow cytometry. RESULTS: TT concentrations were significantly lower in the DM group (13.8 ± 4.7 nmol/l) than in the healthy (17.1 ± 6.1 nmol/l) and non-diabetes groups (15.8 ± 6.0 nmol/l; all P < 0.01). FT, SHBG, AR-positive proportion (AR%) and AR fluorescence intensity showed a decreasing trend among the healthy, non-DM and DM groups, but the differences were not significant. TT, E(2), E(2)/testosterone and SHBG were negatively correlated with blood glucose. SHBG was positively correlated and TT and AR% were negatively correlated with the course of DM. Logistic multiple regression analysis revealed that age, waist/hip ratio, FSH, SHBG and AR% are potential risk factors for DM. CONCLUSIONS: Low levels of TT, SHBG and AR may be potential risk factors for DM in elderly men.

Changes in Home Blood Pressure Monitored Among Elderly Patients With Hypertension During the COVID-19 Outbreak: A Longitudinal Study in China Leveraging a Smartphone-Based Application.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted clinical care worldwide. Evidence of how this health crisis affected common conditions like blood pressure (BP) control is uncertain. METHODS: We used longitudinal BP data from an ongoing randomized clinical trial to examine variations in home BP monitored via a smartphone-based application (app) in a total of 7394 elderly patients with hypertension aged 60 to 80 years stratified by their location in Wuhan (n=283) compared with other provinces of China (n=7111). Change in morning systolic BP (SBP) was analyzed for 5 30-day phases during the pandemic, including preepidemic (October 21 to November 20, 2019), incubation (November 21 to December 20, 2019), developing (December 21, 2019 to January 20, 2020), outbreak (January 21 to February 20, 2020), and plateau (February 21 to March 21, 2020). RESULTS: Compared with non-Wuhan areas of China, average morning SBP (adjusted for age, sex, body mass index) in Wuhan patients was significantly higher during the epidemic growth phases, which returned to normal at the plateau. Between-group differences in ΔSBP were +2.5, +3.0, and +2.1 mm Hg at the incubation, developing, and outbreak phases of COVID-19 (P<0.001), respectively. Sensitivity analysis showed a similar trend in trajectory pattern of SBP in both the intensive and standard BP control groups of the trial. Patients in Wuhan also had an increased regimen change in antihypertensive drugs during the outbreak compared with non-Wuhan patients. Expectedly, Wuhan patients were more likely to check their BP via the app, while doctors were less likely to monitor the app for BP control during the pandemic. CONCLUSIONS: Our data demonstrate that the COVID-19 pandemic was associated with a short-term increase in morning SBP among elderly patients with hypertension in Wuhan but not other parts of China. Further study will be needed to understand if these findings extended to other parts of the world substantially affected by the virus. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03015311.

Sex hormones and androgen receptor: risk factors of coronary heart disease in elderly men.

OBJECTIVE: To investigate the variation of sex hormone and its receptor level in elderly male patients with coronary heart disease (CHD) and to evaluate the correlations between CHD and sex hormone as well as sex hormone receptor. METHODS: Altogether 139 male CHD patients (CHD group) aged 60-92 years and 400 healthy men (control group) aged 60-90 years were included in this cross sectional study. The plasma concentrations of dehydroepiandrosterone sulfate (DHEAS), total testosterone (TT), free testosterone (FT), estradiol (E2), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) was tested by flow cytometry. Correlations between CHD and levels of sex hormones and AR were analyzed. RESULTS: Compared with the control group, the levels of DHEAS, TT, FT, SHBG, and the fluorescence intensity of AR in the CHD group significantly reduced (P < 0.05), while the levels of FSH and E2 significantly increased (P < 0.01). Age was negatively correlated with TT (r = -0.28, P = 0.00) and FT (r = -0.17, P = 0.01), while it was positively correlated with SHBG (r = 0.14, P = 0.04) and E2 (r = 0.33, P = 0.00). AR fluorescence intensity was negatively correlated with systolic blood pressure (r = -0.12, P = 0.01). Binary logistic regression analysis showed that TT, SHBG, and AR were all negatively correlated with CHD (P < 0.05). CONCLUSIONS: Elderly male patients with CHD are found to have low levels of DHEAS, TT, FT, SHBG, and AR, while high concentrations of E2 and FSH. Low levels of TT and SHBG may be the potential risk factors of CHD in elderly men.

Strategy of blood pressure intervention in the elderly hypertensive patients (STEP): Rational, design, and baseline characteristics for the main trial.

The optimal systolic blood pressure (SBP) treatment target in elderly people is full of challenge, and non-adherence is one major cause of uncontrolled BP. The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial is a multi-center, randomized controlled trial that aims to examine whether an intensive treatment (110 ≤ SBP < 130 mmHg) will provide more benefits in lowering cardiovascular events than a mild treatment (130 ≤ SBP < 150 mmHg) among people aged 60-80 years. From January 10, 2017 to December 31, 2017, 8511 patients with primary hypertension were recruited at 42 clinical centers throughout China and randomly assigned to the intensive or standard treatment in 1:1 ratio, in which clinical sites are considered as a stratification factor in randomization. Participants will be followed for an average of four years. All participants used the same validated home BP device and all centers used the same validated office BP device which can automatically upload the readings to a data center. The hospitals were randomly classified as the smartphone-based App center or usual care center in 1:1 ratio for the secondary purpose to study the effect of App management on BP control. In this trial, mean age of participants was 66.2 ± 4.8 years, 24.1% were in the range of 70-80 years, and 65% were at high-risk with the 10-year Framingham risk score ≥ 15%. In conclusion, STEP will provide evidence not only to address appropriate target of BP control among hypertensive patients aged 60-80 years, but also to assess an effective model of App management for hypertension. Trial Registration number: ClinicalTrials. gov. Unique identifier: NCT03015311.

High serum resistin level may be an indicator of the severity of coronary disease in acute coronary syndrome.

OBJECTIVE: To investigate the correlation between serum resistin level, cardiovascular risk factors and severity of coronary disease in acute coronary syndrome (ACS). METHODS: After evaluated by clinical history, electrocardiography, exercise tolerance tests, laboratory tests, and coronary angiography, 220 consecutive patients with suspected chest pain were divided into normal control group, stable angina pectoris (SAP) group, and ACS group, respectively. Baseline clinical characteristics, including height, weight, waist circumference, hip circumference, white blood cell count, high-sensitive C-reactive protein (hsCRP), total cholesterol, triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, were compared among three groups. ELISA was used to detect serum resistin levels. Pearson's correlation coefficient analysis was used to assess association between resistin and other traditional cardiovascular risk factors. Multinomial logistic regression analyses were used to define the relationship between serum resistin level and SAP or ACS. RESULTS: Serum resistin level in ACS group (1.18+/-0.48 microg/L) was significantly higher than that in normal control and SAP groups (0.49+/-0.40 and 0.66+/-0.40 microg/L; P<0.01). Only in ACS group, increased serum resistin level was significantly correlated with hsCRP (r=0.262, P=0.004) and white blood cell count (r=0.347, P=0.001). Furthermore, serum resistin levels showed a stepwise increase with the number increase of > 50% stenosed coronary vessels. Multinomial logistic regression test demonstrated that serum resistin was a strong risk factor for ACS (OR=29.132, 95 % CI: 10.939-77.581, P<0.001). CONCLUSION: These findings suggested the potential role of resistin in atherosclerosis and especially its involvement in ACS.

Drug therapy of paroxysmal atrial fibrillation in the elderly over 75 years old.

OBJECTIVE: To investigate the effectiveness and safety of various agents on paroxysmal atrial fibrillation in the elderly over 75 years old. METHODS: Totally 264 in-patients (75-91 years old, 185 males and 79 females) with atrial fibrillation history of less than 7 days were enrolled in this study. A total of 611 atrial fibrillation episodes were recorded, but 130 episodes (22.3%) of atrial fibrillation were auto-converted to sinus rhythm. The rest 481 episodes of atrial fibrillation were divided into six groups based on the drug used. RESULTS: The cardioversion ratio of atrial fibrillation were 9.5%, 46.9%, 71.7%, 55.9%, 32.7%, and 73.6% in control, cedilanid, amiodarone, propafenone, verapamil, and quinidine groups, respectively. Ventricular rate control were 5.4%, 83.6%, 84.9%, 77.9%, 78.8%, and 11.3% in those groups, respectively. The total effective rates of amiodarone and cedilanid groups were the highest. When the ventricular rate was controlled to below 90 bpm, the patients would almost complain of no discomfort. No severe side-effect was observed in each group. CONCLUSION: Amiodarone and cedilanid may be the proper drugs for the treatment of paroxysmal atrial fibrillation in the elderly. The above antiarrhythmics in each therapeutic group were relatively safe and effective.

High prevalence of aspirin resistance in elderly patients with cardiovascular disease (CVD) and hyperhomocysteinaemia.

Although aspirin resistance is well reported in CVD, little is known about aspirin response in elderly patients with hyperhomocysteinaemia. The aim of the present study was to explore the prevalence of aspirin resistance in elderly patients with CVD and hyperhomocysteinaemia. A total of 370 elderly patients with CVD were recruited. The study included 216 patients with hyperhomocysteinaemia and 154 patients with normohomocysteinaemia receiving daily aspirin therapy (≥ 75 mg) over 1 month. The effect of aspirin was assessed using by light transmission aggregometry (LTA). Aspirin resistance was defined as ≥ 20% arachidonic acid induced aggregation according to LTA. Aspirin resistance was defined in 48 (13.0%) of 370 patients. The prevalence of aspirin resistance was higher in hyperhomocysteinaemic patients than normohomocysteinaemic patients (16.7% vs. 7.8%, odds ratio (OR)=2.367; 95% confidence interval (CI)=1.188-4.715, p=0.012). In the multivariate logistic regression analysis, hyperhomocysteinaemia (OR=2.406, 95% CI=1.201-4.820, p=0.013) was a significant risk factor for aspirin resistance. A significant number of CVD patients with hyperhomocysteinemia are resistant to aspirin therapy. Hyperhomocysteinemia is a significant risk factor for aspirin resistance in elderly patients with CVD.