Comparison of BP variability, cumulative BP, and BP trajectory for predicting cardiovascular events in the general population.

OBJECTIVE: Systolic blood pressure variability (SBPV), cumulative systolic BP (cumSBP), and systolic blood pressure trajectory (trajSBP) are major indices describing characteristics of BP changes. The aim of this study was to compare their discrimination abilities for cardiovascular (CV) events. METHODS: In 51698 subjects, associations were assessed using Cox regression in the overall cohort and Framingham risk score (FRS) stratified groups. Individuals with <10%, 10%-20%, and >20% 10-year CV risk were categorized into the low-, intermediate-, and high-risk group, respectively. Discrimination capabilities were evaluated using the area under curve (AUC), Harrell's C index, net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: Within a mean follow-up of 6.83 ± 0.89 years, 2330 participants had CV events, and all three markers were significantly associated with CV events. TrajSBP provided the best additional discriminative value for CV events, with improvements of 1.54% in AUC%, 0.01 in Harrell's C, 37.52% in NRI%, and 0.59% in IDI%. CumSBP had good additional discriminative capability in the intermediate to high FRS groups, but the effect sizes were smaller than those of trajSBP. Although, SBPV improved the predictive capabilities in the low-to intermediate-risk groups, the effect sizes were much smaller than those of the other indices. Sensitivity analyses excluding patients who underwent antihypertensive therapy revealed similar patterns but higher effect sizes than in the overall population. CONCLUSION: TrajSBP provides the best additional discrimination capabilities based on traditional risk profiles and may assist the risk stratification and individual prediction for future CV events.

Brachial-ankle pulse wave velocity trajectories in a middle-aged population.

Objective: The "trajectory" phenotype was observed in several cardiovascular risk factors with aging. We aim to identify multiple brachial-ankle Pulse Wave Velocity (baPWV) trajectory phenotypes and assess their determinants. Methods: Among 5,182 participants with baPWV measurements (2010-2016) at no less than three time points in Kailuan Study, we derived baPWV trajectory pattern using SAS Proc Traj program. We applied the lowest Bayesian information criterion to identify the best typing model, related the identified trajectory pattern to baseline and changes in characteristics. Results: Among 5.3 ± 1.7 years follow-up, four distinct baPWV trajectories were identified as low (1,961,37.8%), medium-low (1,846,35.6%), medium-high (1,024,19.8%), and high (351,6.8%) groups. In the stepwise models, mean arterial pressure and age were the main determinators of the trajectory patterns, with a Δpseudo-R2 of 0.335 and 0.164, respectively. With the low trajectory group as reference and multivariable adjustment, odd ratios of medium low, medium high and high associated with 1 mmHg increment of mean arterial pressure were 1.08(95%CI: 1.07-1.09), 1.13(1.12-1.14), and 1.16(1.15-1.18). The estimates for age were 1.08(1.07-1.10), 1.20(1.18-1.21) and 1.28(1.26-1.31). Additionally, baseline resting heart rate, low-density lipoprotein cholesterol, fasting blood glucose, hypersensitive C-reaction protein and uric acid, and changes in mean arterial pressure, resting heart rate, fasting blood glucose, and uric acid were positively associated with the trajectory, while BMI was negatively associated. Conclusions: The changes in baPWV overtime followed a "trajectory" pattern, mainly determined by mean arterial pressure and age.

Influence of Hypersensitive C-Reactive Protein on the Effect of Continuous Antihypertensive Pharmacological Therapy.

ABSTRACT: Systemic chronic inflammation, represented by hypersensitive C-reactive protein (hsCRP), is an essential contributing factor to hypertension. However, the influence of hsCRP levels on the effect of antihypertensive pharmacological therapy remains unknown. We evaluated hsCRP levels in 3756 newly diagnosed, untreated hypertensive subjects. Participants were grouped by tertiles of hsCRP and were randomly treated with nitrendipine + captopril, nitrendipine + spironolactone hydrochlorothiazide + captopril, and hydrochlorothiazide + spironolactone. Blood pressure (BP) was recorded every 2 weeks. A multivariate mixed linear model was used to evaluate the impact of baseline hsCRP levels on the continuous antihypertensive effect. After 3, 6, 9, and 12 months of continuous antihypertensive treatment, no significant difference was observed in BP decline among the different hsCRP groups. We identified interactions between baseline hsCRP levels and follow-up time. After adjusting for conventional risk factors and the interactions between hsCRP and follow-up time, there was no significant association between baseline hsCRP level and antihypertensive effects at 0-6 months of follow-up. However, from 6 to 12 months, subjects with higher baseline hsCRP levels exhibited a more marked BP-lowering effect ( P < 0.001 at 9 months, P = 0.002 at 12 months). Overall, there exist interaction effects between baseline hsCRP levels and follow-up time. Individuals with higher baseline hsCRP levels may exhibit a better response to antihypertensive therapy.

Arterial Stiffness Preceding Diabetes: A Longitudinal Study.

RATIONALE: Previous studies on the relationship between diabetes and arterial stiffness were mostly cross-sectional. A few longitudinal studies focused on one single direction. Whether the association between arterial stiffness and diabetes is bidirectional remains unclear to date. OBJECTIVE: To explore the temporal relationship between arterial stiffness and fasting blood glucose (FBG) status. METHODS AND RESULTS: Included were 14 159 participants of the Kailuan study with assessment of brachial-ankle pulse wave velocity (baPWV) from 2010 to 2015, and free of diabetes, cardiovascular and cerebrovascular diseases, and chronic kidney disease at baseline. FBG and baPWV were repeatedly measured at baseline and follow-ups. Cox proportional hazard regression model was used to estimate hazard ratios and 95% confidence intervals (CIs) of incident diabetes across baseline baPWV groups: <1400 cm/s (ref), 1400≤ baPWV <1800 cm/s, and ≥1800 cm/s. Path analysis was used to analyze the possible temporal causal relationship between baPWV and FBG, among 8956 participants with repeated assessment of baPWV and FBG twice in 2010 to 2017. The mean baseline age of the observed population was 48.3±12.0 years. During mean 3.72 years of follow-up, 979 incident diabetes cases were identified. After adjusting for potential confounders, the hazard ratio (95% CI) for risk of diabetes was 1.59 (1.34-1.88) for the borderline arterial stiffness group and 2.11 (1.71-2.61) for the elevated arterial stiffness group, compared with the normal ideal arterial stiffness group. In the path analysis, baseline baPWV was associated with follow-up FBG (the standard regression coefficient was 0.09 [95% CI, 0.05-0.10]). In contrast, the standard regression coefficient of baseline FBG for follow-up baPWV (ß=0.00 [95% CI, -0.02 to 0.02]) was not significant. CONCLUSIONS: Arterial stiffness, as measured by baPWV, was associated with risk of developing diabetes. Arterial stiffness appeared to precede the increase in FBG.

Blood Pressure Classification of 2017 Associated With Cardiovascular Disease and Mortality in Young Chinese Adults.

The American College of Cardiology/American Heart Association introduced new guidelines for blood pressure (BP) classification in 2017. We explored associations between the newly defined categories and eventual cardiovascular disease (CVD) events, stroke, and all-cause mortality in young Chinese adults. In the community-based Kailuan Study, 16 006 participants aged 18 to 40 years and examined at baseline in 2006/2007 underwent 2-yearly follow-up examinations up to 2016 to 2017. Taking the highest BP reading recorded by manual sphygmomanometry at baseline in 2006 to 2007, we categorized the BP according to the new guidelines. Outcome parameters were CVD events, stroke, and all-cause mortality. During follow-up (mean: 10.9±0.63 years), we observed 458 events (CVD, 167; stroke, 119; and all-cause death, 172). After multivariable adjustment, hazard ratios for CVD events were for elevated BP 0.80 (95% CI, 0.28-2.30), stage 1 hypertension 1.82 (95% CI, 1.12-2.94), and stage 2 hypertension 3.54 (95% CI, 2.18-5.77) versus normal BP. Similar results were obtained for stroke and all-cause death. In Cox regression analysis with BP category entered as time-dependent covariate, stage 1 hypertension was not associated with increased risk (P>0.10). In the subgroup of individuals taking antihypertensive medication during follow-up, none of the BP categories was significantly associated with the incidence of CVD events. During a mean follow-up of 10.9 years, the newly defined category of stage 1 hypertension in young untreated Chinese adults aged <40 years at baseline was associated with an increased risk for CVD, stroke, and all-cause mortality. This increased risk occurred, however, after progression to stage 2 hypertension. The data may help validating the new BP classification system for young adult Chinese.

Blood Pressure Variability Is Associated with Hearing and Hearing Loss: A Population-Based Study in Males.

Blood pressure (BP) has been well documented to be associated with hearing loss previously. However, the role of blood pressure variability (BPV, representing BP fluctuation over a time period) on hearing remains unknown. We aimed to evaluate the relationship between BPV and hearing in Chinese population. We included 8646 male subjects from a population-based study (the Kailuan study). BP was measured every two years at routine physical examinations from 2006 to 2015. Based on five annual BP measurements, BPV was estimated by standard deviation of BP (SD), coefficient of the variation of BP (CV), and variation independent of mean of BP (VIM). Hearing was estimated by pure-tone average threshold (PTA) at low, intermediate, and high frequencies in the year of 2014. Regression models were used to evaluate the relationship between BPV and hearing. The results showed that PTAs and percentages of hearing loss at low, intermediate, and high frequencies grew gradually with increasing systolic SD (SSD) (p<0.05). After adjusting for multiple covariates, multivariate regression analyses demonstrated that variations of SBP (SSD, SCV, and VIMSBP) were all positively correlated with PTA at intermediate and high frequencies (p<0.05). Each SD increase in SSD, SCV, and VIMSBP was also positively associated with hearing loss at intermediate and high frequencies. No significant correlation was observed between variations of DBP and hearing. These findings suggest that increase in long-term BPV is associated with hearing and hearing loss. Trial registration number: Kailuan study (ChiCTRTNC-11001489).

[The linkage disequilibrium of four loci in hepatic lipase promoter gene of cerebral infarction patients in Shanghai].

OBJECTIVE: To investigate the single nucleotide polymorphism (SNP), the distribution of their haplotypes and linkage disequilibrium of hepatic lipase (HL) gene promoter 250G/A, 514C/T, 710T/C and 763A/G in cerebral infarction patients of Shanghai. METHODS: Peripheral blood sample were collected from 133 patients with cerebral infarction and 112 healthy controls in Shanghai. The HL gene polymorphism was analyzed by polymerase chain reaction- restriction fragment length polymorphism. RESULTS: There were statistically significant differences in genotype and allele frequencies between the healthy controls and the patients with cerebral infarction in -250G/A and -514C/T genotypes and allele frequencies (all P < 0.05). However, there were no significant differences in genotype and allele frequencies in -710T/C and -763A/G between the healthy controls and the patients with cerebral infarction (all P > 0.05). Besides, there was a strong linkage disequilibrium between -250G/A and -514C/T, -710T/C, and -763A/G respectively, between -514C/T and -710T/C and -763A/G respectively, and between -710T/C and -763A/G. When the haplotypes were -250G/-514C, -250G/-710C, -250G/-763G, -514C/-710C, and 514C/-763G respectively, the frequencies in the cerebral infarction group were significantly lower than that in the healthy controls. When the haplotype was -250A/-514T, -250A/-710T, -250A/-710C, -250A/-763G, -514T/-710C, -514T/-763G, and -710T/-763G respectively, the frequencies in the cerebral infarction group were significantly higher than those in the healthy controls. CONCLUSION: There are significant haplotypes and linkage disequilibrium among the four SNPs of HL gene in the cerebral infarction patients of Shanghai. The haplotypes GC, GG, and CC lower the incidence rate of cerebral infarction, while the haplotypes AT, AC, AG, TC, and TG increase the incidence rate of cerebral infarction.

Polymorphism of the D4Z4 locus associated with facioscapulohumeral muscular dystrophy 1A in Shanghai population.

OBJECTIVE: To investigate the D4Z4 repeats on chromosome 4q35 in normal individuals in Shanghai and analysis the polymorphism of the D4Z4 locus. METHODS: The length of D4Z4 repeats on chromosome 4q35 in 191 normal individuals in Shanghai was determined by pulsed-field gel electrophoresis and Southern blotting after double digestion with Eco RI and Bln I. The number of short D4Z4 repeats was counted after partial digestion with Kpn I. RESULTS: Among 191 normal individuals in Shanghai, seventeen showed the size of D4Z4 fragments ranged from 22 to 34 kb, i.e. 8.9% of individuals had fewer numbers of D4Z4 repeats. Of these 17 individuals, sixteen showed the short D4Z4 fragment on chromosome 4q35, and one low D4Z4 fragment was correlated to 4q35--> 10q26 translocation. CONCLUSION: The frequency of individuals having fewer numbers of D4Z4 repeats on chromosome 4q35 in Shanghai population is higher than that in Caucasian population although the short D4Z4 fragment on chromosome 4q35 is associated with facioscapulohumeral muscular dystrophy. These findings suggest that other factors may also contribute to facioscapulohumeral muscular dystrophy.

[Dysferlin deficiency: the cause of limb-girdle muscular dystrophy 2B and Miyoshi myopathy in a Chinese pedigree].

OBJECTIVE: To identify an inbred Chinese pedigree with autosomal recessive muscular dystrophy and analyze the molecular defects. METHODS: Linkage analysis was conducted using short tandem repeat(STR) markers from the regions associated with limb-girdle muscular dystrophy type 2A(LGMD2A) through 2H. Multi-Western blot was performed with anti-calpain-3, anti-dysferlin, anti-gamma-sarcoglycan, anti-alpha-sarcoglycan, and anti-dystrophin monoclonal antibodies. Mutation was determined by reverse transcriptase-polymerase chain reaction and sequencing. RESULTS: Two-point linkage analysis showed significant Lod scores with markers from chromosome 2p13, the highest two-point Lod scores were obtained with D2S337 (Z(max)=1.86 at theta=0). Multi-Western blot confirmed dysferlin deficiency of muscle specimen from the proband. Mutation analysis revealed a novel 6429delG mutation on exon 53 of the DYSF gene for the proband. CONCLUSION: The authors identified an inbred Chinese pedigree with Miyoshi myopathy caused by a 6429delG on the DYSF gene. This mutation is predicted to result in premature termination of translation.