Transitions in Metabolic Health and Onset Age of Cardiovascular Diseases.

INTRODUCTION: The cardiometabolic risk associated with metabolically healthy obesity remains the subject of debate. It is unclear whether changes in metabolically healthy obesity status affect premature cardiovascular disease (CVD) risk. Authors aimed to investigate the association of metabolically healthy obesity and its transition over time with incident CVD by age at onset. METHODS: In a community-based, prospective cohort study, 54,441 adults without CVD in or before 2010 were followed for incident CVD until 2020. This sample was analyzed in 2022. Four age groups were examined (<55, 55-65, 65-75, and ≥75 years) for CVD onset. In each age group, participants were cross-classified by BMI categories and metabolic health. The Cox proportional hazards model with age as the underlying time scale was used to examine the associations of metabolic health status and its transition with CVD across BMI categories. RESULTS: During a median follow-up of 9.59 years, 3,038 participants developed CVD. Individuals with metabolically unhealthy obesity at baseline had the highest hazard ratio for CVD onset at any age, ranging from 2.68 (95% CI=2.02, 3.55) for CVD onset in those aged <55 years to 1.55 (95% CI=1.09, 2.10) for CVD onset in those aged ≥75 years. Individuals who had metabolically healthy obesity at baseline or even remained metabolically healthy during 2006-2010 were still at increased risk of premature CVD, and the association attenuated with increasing age of CVD onset. CONCLUSIONS: The metabolically healthy obesity phenotype is dynamic and its transition to a metabolically unhealthy phenotype or even stable metabolically healthy obesity is associated with an increased risk of CVD. The associations were more evident for CVD onset at younger ages.

Resting heart rate and risk of atrial fibrillation in Chinese general population: Kailuan prospective cohort study.

OBJECTIVE: Previous research has shown an association of higher heart rate with an increased risk of atrial fibrillation (AF). However, the relationship between resting heart rate (RHR) and AF is unknown. The aim of this study was to investigate the association between RHR and AF in the general population of China. DESIGN: Prospective observational cohort study. SETTING: Community based. PARTICIPANTS: A total of 46 126 individuals from the Kailuan study who participated in the first three surveys (2006/2007, 2008/2009 and 2010/2011) and were followed up at 2-year intervals were enrolled. PRIMARY OUTCOME MEASURES: The association between RHR and risk of incident AF was evaluated using Cox proportional hazards regression and restricted cubic spline models. RESULTS: Two hundred and forty-one individuals (0.52%) developed AF during 7.5 years of follow-up. After adjustment for age, sex, low-density and high-density lipoprotein, physical activity, alcohol consumption, smoking status, body mass index, mean systolic blood pressure, and history of diabetes and hypertension, the HRs were 2.32 (95% CI 1.45 to 3.72) for an RHR <60 beats/min and 2.80 (1.13 to 6.94) for an RHR ≥100 beats/min in comparison with an RHR of 70-80 beats/min. Restricted cubic spline models revealed a U-shaped relationship between RHR and incident AF. CONCLUSION: These findings indicate that RHR and incident AF have a U-shaped relationship in the Chinese general population. Both lower and higher RHRs were associated with an increased risk of AF.

Prevalence and clinical characteristics of atrial fibrillation in hospitalized patients with coronary artery disease and hypertension: a cross-sectional study from 2008 to 2018.

BACKGROUND: The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF. METHODS: This cross-sectional study was conducted in Chinese People's Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD. RESULTS: The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28% (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2 DS 2 -VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P  < 0.01), but remained at a relatively low level. CONCLUSIONS: AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.

Combined effect of inter-arm systolic blood pressure difference and carotid artery plaque on cardiovascular diseases and mortality: A prospective cohort study.

Objectives: Previous studies have confirmed the relations between inter-arm systolic blood pressure difference (IASBPD) and carotid artery plaque with the risk of cardiovascular diseases (CVD). But it is unclear whether the combined effect of IASBPD and carotid artery plaque further increases the risk of CVD and all-cause mortality. Materials and methods: We enrolled 4,970 participants (≥40 years old) in the prospective Kailuan study. All participants underwent dual-arm blood pressure and carotid artery ultrasounds. IASBPD was the absolute value of the difference between dual-arm blood pressure. All the participants were divided into four groups according to their IASBPD levels and the presence or absence of carotid artery plaque and Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident CVD and all-cause mortality. Results: During a median follow-up of 7 years, 179 CVD events and 266 deaths occurred. Multivariable Cox Regression showed that participants with IASBPD ≥ 10 mmHg and plaque had a significantly higher incidence of CVD, cerebral infarction (CI), and myocardial infarction (10, 7.27, and 1.36%, respectively). After adjusting for covariates, the IASBPD ≥ 10 mmHg and carotid plaque group significantly increased risks for CVD (HR 2.38; 95% CI, 1.40∼4.05), CI (HR, 2.47; 95% CI, 1.31∼4.67), and all-cause mortality (HR, 2.08; 95% CI, 1.20∼3.59). Conclusion: Our study indicated that the combination of IASBPD and carotid artery plaque was associated with incident CVD and all-cause mortality.

Visit-to-visit SBP variability and risk of atrial fibrillation in middle-aged and older populations.

OBJECTIVE: We sought to examine the relationship between visit-to-visit variability of SBP and incident atrial fibrillation in middle-aged and older population. METHODS: This prospective cohort study included 26 999 participants aged 50 years or older at study entry. Visit-to-visit variability of SBP was defined as the average real variability (ARV) of three values of SBP from the examinations of 2006, 2008, and 2010. We categorized participants into four groups according to the quartiles of ARV. Incident atrial fibrillation cases were identified via ECG during biennial resurveys, and reviewing medical insurance record and discharge registers. We used Cox regression models to evaluate the hazard ratios and 95% confidence intervals (CI) for incident atrial fibrillation. RESULTS: After an average follow-up of 9.24 years, a total of 420 atrial fibrillation cases were identified. The incidence of atrial fibrillation from the lowest to the highest quartiles of SBP variability were 1.23, 1.53, 1.81 and 2.19 per 1000 person-years, respectively. After adjusting for potential confounders, including mean blood pressure, we found a graded association between SBP variability and risk of atrial fibrillation. Participants in the third quartile and the highest quartile were associated with 35 and 53% higher risk of developing atrial fibrillation, respectively, compared with participants in the lowest quartile [hazard ratio (95% CI), 1.35 (1.01-1.82) and 1.53 (1.15-2.04)]. The results persisted across sensitivity analyses. CONCLUSION: Increased visit-to-visit variability of SBP is a strong predictor of incident atrial fibrillation in middle-aged and older population. Evaluation of long-term SBP variability could help to identify individuals at higher risk of atrial fibrillation.

Combined effect of visit-to-visit variations in heart rate and systolic blood pressure on all-cause mortality in hypertensive patients.

Elevated resting heart rate (RHR) and systolic blood pressure (SBP) are independent risk factors for all-cause mortality in hypertensive patients. However, the association of the visit-to-visit variation (VVV) in SBP and RHR with the risk of mortality in hypertensive patients remains unknown. The aim of this study was to investigate the effects of the VVVs in SBP and RHR on the risk of all-cause mortality. We enrolled 16,602 hypertensive patients from the Kailuan cohort study who underwent three health examinations from 2006 to 2010. The VVVs in SBP and RHR were defined by the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability parameters (e.g., a score of 2 indicated high variability in two parameters). Cox proportional hazards models were used to estimate hazard ratios for mortality. High VVVs in SBP and RHR were associated with an increased risk of all-cause mortality in hypertensive patients. In the multivariable-adjusted model comparing a score of 0 with a score of 2, the hazard ratios (95% confidence intervals (CIs)) for all-cause mortality were 1.38 (1.11-1.69), 1.52 (1.24-1.87), 1.32 (1.07-1.63), and 1.43 (1.16-1.75) using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability, respectively. High VVVs in SBP and RHR constituted an independent risk factor for all-cause mortality in hypertensive patients. High VVVs in SBP and RHR additively increased the risk of all-cause mortality in hypertensive patients.

Frequency of Visit-to-Visit Variability of Resting Heart Rate and the Risk of New-Onset Atrial Fibrillation in the General Population.

Resting heart rate (RHR) has been an established predictor for atrial fibrillation (AF). However, the association of visit-to-visit heart rate variability (VVHRV) with new-onset AF risk over long term remains unclear. Our study investigates the relation of VVHRV to new-onset AF in general population in the prospective study of the Kailuan cohort. A total of 46,126 individuals without arrhythmia were included. They underwent 3 health examinations from 2006 to 2010 and performed follow up. VVHRV was measured by coefficient of variation (CV), variability independent of the mean (VIM), and standard deviation (SD). Participants were separately divided into 5 categories by quintiles of visit-to-visit RHR-CV, RHR-VIM and RHR-SD. Multivariate Cox regression and restricted cubic spline models were performed to establish the association between VVHRV and new-onset AF. 241 new-onset AF occurred during a median follow-up of 7.54 years. The incidence of new-onset AF in the group of the lowest (Q1) and highest quintiles (Q5) of RHR-CV were higher than that in other groups. The HRs for the new-onset AF were 2.07 (95% CI, 1.34-3.21, p < 0.01), in the highest quintile group(Q5) compared with group Q2, and 1.89(95% CI, 1.20-2.97, p < 0.01) in the lowest quintile group(Q1) compared with group Q2. The risk for new-onset AF showed a similar trend using RHR-VIM (p < 0.01) and RHR-SD (p < 0.05) parameters. Further sensitivity analyses indicated the consistent results in subjects without prior cardiovascular disease and without taking beta blockers or CCB. To match the covariates, analyses were also performed by propensity score matching, and prominent trends were also found in RHR-SD and RHR-VIM. In conclusion, the study indicated that higher and lower VVHRV were associated with the increasing risk of new-onset AF, which supporting a U-shaped curve existence.

Early onset of hyperuricemia is associated with increased cardiovascular disease and mortality risk.

BACKGROUND: Hyperuricemia is associated with cardiovascular mortality, but the association of the age at hyperuricemia onset with cardiovascular disease (CVD) and mortality is still unclear. OBJECTIVE: The purpose of this study was to examine the associations of hyperuricemia onset age with CVD and all-cause mortality. METHODS: A total of 82,219 participants free of hyperuricemia and CVD from 2006 to 2015 in the Kailuan study were included. The analysis cohort comprised 18,311 new-onset hyperuricemia patients and controls matched for age and sex from the general population. Adjusted associations were estimated using Cox models for CVD and all-cause mortality across a range of ages. RESULTS: There were 1,021 incident cases of CVD (including 215 myocardial infarctions, 814 strokes) and 1459 deaths during an average of 5.2 years of follow-up. Patients with hyperuricemia onset at an age < 45 years had the highest hazard ratios (HRs) (1.78 (1.14-2.78) for CVD and 1.64 (1.04-2.61) for all-cause mortality relative to controls). The HRs of CVD and all-cause mortality were 1.32 (1.05-1.65) and 1.40 (1.08-1.81) for the 45-54 years age group, 1.23 (0.97-1.56) and 1.37 (1.11 to 1.72) for the 55-64 years age group, and 1.10 (0.88-1.39) and 0.88 (0.76-1.01) for the ≥ 65 years age group, respectively. CONCLUSIONS: The age at hyperuricemia onset was identified as an important predictor of CVD and all-cause mortality risk, and the prediction was more powerful in those with a younger age of hyperuricemia onset. Early onset of hyperuricemia is associated with increased cardiovascular disease and mortality risk.

Effect of Brachial-Ankle Pulse Wave Velocity Combined with Waist-to-Hip Ratio on Cardiac and Cerebrovascular Events.

BACKGROUND: Abdominal obesity and brachial-ankle pulse wave velocity (baPWV) are indicators of atherosclerosis. But few studies have shown the relationship between baPWV combined with waist-hip ratio (WHR) and cardiac-cerebrovascular events (CCVEs). METHODS: A total of 18944 subjects from Kailuan study were enrolled in this study. Follow-up was conducted three times over 4.82±1.92 years. All the participants were divided into 4 groups according to baPWV and WHR status on baseline: Q1 (normal baPWV, normal WHR), Q2 (normal baPWV, increased WHR), Q3 (increased baPWV, normal WHR) and Q4 (increased baPWV, increased WHR). The incidence and risk factors and further analysis of hypertension subgroups were analyzed. RESULTS: During follow-up, 88 myocardial infarctions (MI), 278 cerebral ischemic strokes (CI), 285 strokes and 371 CCVEs occurred, with the cumulative incidence of 0.46%, 1.47%, 1.50%, and 1.96%, respectively. Multivariate Cox regression analysis revealed the risk of CI, stroke and CCVEs was higher in patients with increased baPWV and increased WHR than in the other three groups, followed by the Q3 group (increased baPWV, normal WHR) and Q2 group (normal baPWV, increased WHR) group (all adjusted P<0.01). Further hypertension subgroups analysis showed similar results, but differences were more significant among hypertensive patients. Accordingly, the combination of baPWV and WHR increased the risk of total CCVEs, especially in hypertensive patients. CONCLUSIONS: BaPWV and WHR were important risk factors for CCVEs and had synergistic effects. When baPWV increased, WHR may contribute more to the risk of CCVEs in hypertensive patients.

Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study.

OBJECTIVE: We aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in the Chinese population. RESEARCH DESIGN AND METHODS: This study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan Study. All participants were monitored biennially until 31 December 2017. During follow-up, 11,384 participants were diagnosed as having type 2 diabetes. For each case subject, one control subject was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% CIs of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes versus control subjects across age-groups. RESULTS: During a median follow-up of 5.57 years, 1,794 incident events (907 CVD events, of which there were 725 strokes and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age <45 years had the highest relative risks of CVD and all-cause mortality relative to the matched control subjects, with AHRs of 3.21 (95% CI 1.18-8.72) for CVD, 2.99 (95% CI 1.01-9.17) for stroke, and 4.79 (95% CI 1.95-11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age. CONCLUSIONS: The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age-groups, and the associations were more evident in younger-onset type 2 diabetes.

Relationship between resting heart rate and incident heart failure in patients with hypertension: The Kailuan Cohort Study in China.

An elevated heart rate increases the risk of cardiovascular disease, but the relationship between resting heart rate (RHR) and the risk of heart failure (HF) in hypertensive patients is unclear. This study was performed to assess the relationship between elevated RHR and incident HF in hypertensive patients. In total, 16 286 hypertensive patients from the Kailuan cohort were enrolled and underwent three physical examinations. According to mean RHR based on quartile, the hypertensive patients were divided into four groups: Q1 (mean RHR ≤ 69 bpm), Q2 (69 bpm < mean RHR ≤ 74 bpm), Q3 (74 bpm < mean RHR ≤ 79 bpm), and Q4 (mean RHR > 79 bpm). The cumulative mortality rate was analyzed by using the Kaplan-Meier method, with comparisons among RHR quartiles. Cox proportional hazards regression models and restricted cubic spline models were established to evaluate the association between RHR and risk of incident HF. After adjustment for confounders, the hazard ratio (HR) for HF was 1.97(95% CI: 1.28-3.04, P < .001) in the fourth quartile compared to the first quartile. Each 1-standard deviation [10 (beats/min)] increase in RHR was associated with a 40% increase in the risk of incident HF. Restricted cubic spline models presented a linear relationship between RHR and incident HF. Our study suggests that elevated RHR is associated with an enhanced risk of HF in hypertensive patients.

MicroRNA-29a attenuates angiotensin-II induced-left ventricular remodeling by inhibiting collagen, TGF-ß and SMAD2/3 expression.

BACKGROUND: Left ventricular (LV) remodeling is the most common target organ damage in hypertension. Previously, our study found that plasma microRNA-29a (miR-29a) level was associated with the LV remodeling in hypertensive patients. However, the causal relationship between miR-29a and LV remodeling remains unknown. Thus, the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling. METHODS & RESULTS: Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively. Then the mice were subjected to angiotensin-II (AngII) induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks. AngII-induced LV remodeling mice as the model group (n = 9). Age-matched male SPF C57/BL6J mice (6-8 weeks old) were treated with the pumping of saline as a vehicle (n = 6). In vivo, overexpression miR-29a ameliorated AngII-induced LV remodeling, while knockdown miR-29a deteriorated LV remodeling. Simultaneously, we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area, indicating that miR-29a has an antagonistic effect on cardiac hypertrophy. Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III. Moreover, the expression of transforming growth factor-ß (TGF-ß) and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice. CONCLUSIONS: Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition, TGF-ß, and phosphorylated SMAD2/3 expression. Thus, intervention miR-29a may be a therapeutic target for attenuating LV remodeling.