Yiwu Zhou

Northern Shanghai Study: cardiovascular risk and its associated factors in the Chinese elderly—a study protocol of a prospective study design

Introduction Cardiovascular (CV) diseases are the leading cause of death and disability in the world. Increasing lifespans and ageing populations also contribute to an increasing CV burden. However, in China, there were few well-designed cohort studies focusing on the elderly population, let alone an established CV risk score. The objective of this study is to establish a CV risk score based on a community-dwelling Chinese elderly population, determining the profile of the associated CV risk factors and target organ damages (TODs), so as to guide the later intervention. Methods and analysis The Northern Shanghai Study is an ongoing prospective community-based study. After enrolment, clinical examination, anthropometric measurement and a questionnaire will be administered to each participant at baseline and after every 2 years in the follow-up. Our tests and examinations include: blood/urine sample and biochemical measurements, office blood pressure recording, carotid ultrasonograph, echocardiograph, pulse wave velocity, pulse wave analysis, 4-limb blood pressure recording, body mass index, etc. Baseline measurement will also include the assessments on TODs and the conventional CV risk factors. In the follow-up, the incidence of CV events and mortality will be recorded. The Northern Shanghai Risk Score will be calculated, with considerations on CV risk factors and TODs. Ethics and dissemination This study was approved by the Shanghai Tenth Peoples Hospital Institutional Review Board. All participants signed a written consent form. Trial registration number NCT02368938; Pre-results.

Comparison of Carotid‐Femoral and Brachial‐Ankle Pulse‐Wave Velocity in Association With Target Organ Damage in the Community‐Dwelling Elderly Chinese: The Northern Shanghai Study

Background Carotid‐femoral pulse‐wave velocity (cf‐PWV) and brachial‐ankle PWV (ba‐PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of hypertensive target organ damage (TOD) with cf‐PWV and ba‐PWV. Methods and Results A total of 1599 community‐dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf‐PWV and ba‐PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima‐media thickness, arterial plaque, creatinine clearance rate, and urinary albumin‐creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba‐PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf‐PWV and ba‐PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf‐PWV, but not ba‐PWV, was significantly associated with carotid intima‐media thickness and creatinine clearance rate (P<0.05). When cf‐PWV and ba‐PWV were both or separately put into the same full‐mode model after adjustment for confounders, only cf‐PWV, but not ba‐PWV, showed significant association with carotid intima‐media thickness and creatinine clearance rate (P<0.05). Similar results were observed in logistic regression analysis. Conclusions Taken together, in the community‐dwelling elderly Chinese, cf‐PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba‐PWV. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02368938.

PULSE PRESSURE AMPLIFICATION AND AUGMENTATION INDEX IN ASSOCIATION WITH CARDIAC STRUCTURAL AND FUNCTIONAL DAMAGE: THE NORTHERN SHANGHAI STUDY

Objective: To investigate and compare the associations of pulse pressure amplification (PPA) and augmentation index (Aix) with asymptomatic cardiac structural and functional damage in an elderly Chinese population. Figure. No caption available. Design and method: 1940 participants (mean age of 71.6 years) were included in the present study. Central blood pressure (BP) parameters were measured by SphygmoCor device. PPA and Aix were calculated as the ratio of central and brachial pulse pressures and the ratio of augmentation pressure and aortic pulse pressure, respectively. Cardiac structural and functional parameters including left ventricular mass index (LVMI), the ratio of peak early diastolic transmitral flow velocity and early diastolic lateral mitral annular velocity (E/Ea), were evaluated using standardized methods. Results: In correlation analysis, both PPA and Aix significantly correlated with LVMI and E/Ea ratio. When PPA and Aix separately put into same multivariate full-mode linear regression models, both PPA and Aix significantly associated with LVMI (regression coefficient [&bgr;] = 4.664, per 10% increase of PPA, P < 0.001; &bgr; = 1.998, per 10% increase of Aix, P = 0.02) and E/Ea ratio (&bgr; = 0.499, per 10% increase of PPA, P < 0.01; &bgr; = 0.152, per 10% increase of Aix, P = 0.18). When PPA and Aix both put into same multivariate stepwise linear regression models, only PPA were stayed in the model. When PPA and Aix separately put into same multivariate full-mode logistic regression models, only PPA was significantly associated with left ventricular hypertrophy (Odds ratio[OR]:1.242, 95% confidence interval[CI]:1.026–1.505, per 10% increase of PPA) and dysfunction (OR: 1.407, 95%CI: 1.087–1.820, per 10% increase of PPA). When PPA and Aix both put into same multivariate stepwise logistic regression models, only PPA were stayed in the model. In all multivariate models, brachial systolic BP was included and significantly associated with cardiac damage. Conclusions: PPA showed stronger BP-independent association with cardiac structural and functional damage than Aix.

ASSOCIATION OF ASYMPTOMATIC TARGET ORGAN DAMAGES WITH SECRETED FRIZZLED RELATED PROTEIN 5 IN THE ELDERLY: THE NORTHERN SHANGHAI STUDY

Objective: Secreted frizzled related protein 5 (SFRP5) is a novel anti-inflammatory adipokine which is implicated in metabolic and cardiovascular disease (CVD). However, little is known about the relevance of SFRP5 with asymptomatic hypertensive target organ damages (TOD). We aimed to investigate the association between SFRP5 and TOD in a large population study. Figure. No caption available. Design and method: Associations between plasma SFRP5 and cardiovascular risk factors as well as TOD were investigated in 1745 participants from Northern Shanghai Study. Plasma SFRP5 level was measured by an enzyme-linked immunosorbent assay. Results: Plasma SFRP5 level was negatively associated with body mass index, waist/hip ratio and fasting blood glucose (all P < 0.001). Lower plasma SFRP5 level was observed in men than in women (4.19 vs 5.13 ng/ml, P < 0.001), in smokers than in nonsmokers (4.34 vs 4.78 ng/ml, P < 0.05). Additionally, plasma SFRP5 level was also lower in diabetes than those without diabetes (4.30 vs 4.81 ng/ml, P < 0.05). Further, an inverse association was observed between SFRP5 and pulse wave velocity as well as carotid intima-media thickness (both P < 0.05). Moreover, multivariate logistic regression analysis showed lower SFRP5 level was associated with increased arterial stiffness in the elderly (OR 0.83, 95% CI 0.71 to 0.99 per 1-SD increase, P < 0.05). Conclusions: Plasma SFRP5 level was inversely correlated with conventional cardiovascular risk factors and low plasma SFRP5 was also significantly associated with arterial stiffening in the elderly Chinese population.

COMPARISON OF ANKLE-BRACHIAL INDEX AND UPSTROKE TIME PER CARDIAC CYCLE IN ASSOCIATION WITH TARGET ORGAN DAMAGE IN ELDERLY CHINESE: THE NORTHERN SHANGHAI STUDY

Objective: Recent studies indicated that upstroke time per cardiac cycle (UTCC) in lower extremity is equivalent to ankle-brachial index (ABI) in diagnosing peripheral arterial disease and in predicting cardiovascular mortality. In the present study, we aim to compare ABI and UTCC in relation to target organ damage (TOD) Figure. No caption available. Design and method: 1841 elderly participants (mean age of 70 years) derived from the Northern Shanghai Study were included in the present study. ABI and UTCC were measured using VP-1000 device (Omron, Japan). TOD including left ventricular hypertrophy and diastolic dysfunction, carotid intima-media thickness and plaque, carotid-femoral pulse wave velocity (CF-PWV) and renal damage, were all evaluated. Results: ABI and UTCC both were significantly correlated with CF-PWV, carotid plaque and eGFR, but not with cardiac damage. Compared with ABI, UTCC showed stronger correlation with CF-PWV. When ABI and UTCC separately put into same multivariate full-mode logistic regression models, both ABI (Odds Ratio [OR]:2.273; 95% Confidence Interval [CI]:1.632–3.165) and UTCC (OR:1.627; 95%CI: 1.182–2.240) significantly associated with carotid plaque, but only UTCC significantly associated with increased CF-PWV (OR:1.664; 95%CI:1.147–2.416) and renal damage (OR:1.625; 95%CI:1.068–2.472). When ABI and UTCC both put into same multivariate stepwise logistic regression models, consistent results were observed. In ROC curve analysis, UTCC was better than ABI in discriminating increased CF-PWV (AUC:0.68 vs. 0.57; P < 0.001) and renal damage (AUC:0.67 vs. 0.60; P = 0.012). Conclusions: Compared with ABI, UTCC showed stronger association with vascular and renal damage in this elderly cohort. In combination with previous findings, UTCC may be a useful tool for diagnosing PAD and stratifying cardiovascular risk.

DETERMINANTS OF RENAL FUNCTIONAL IMPAIRMENT, THE IMPORTANCE OF FASTING PLASMA GLUCOSE CONTROL: THE NORTHERN SHANGHAI STUDY

Objective: Chronic kidney disease is a global health problem. However, the causes of renal functional impairment in the general elderly population remains unclear. The aim of this study was to investigate the determinants of renal functional impairment, within a framework of cardiovascular (CV) risk assessment in a community-dwelling elderly cohort. Design and method: From June 2014 to August 2015, a total of 912 community-dwelling elderly subjects (aged > = 65 years) from the northern Shanghai were recruited. CV risk factors were assessed, and renal function was evaluated by estimated glomerular filtration rate (e-GFR) at baseline and during 2-year follow-up. Rapid decline in e-GFR was defined as an e-GFR slope (decline in e-GFR) > 5 ml/min per 1.73 m2 per year. Results: The average decline in e-GFR was 0.104 ml/min/1.73m2 per year, while the increasing risk of having rapid decline in e-GFR was 1.25-fold every additional year. Decline in e-GFR was significantly different between diabetics and non-diabetics (p = 0.03). In full adjustment model, decline in e-GFR (p = 0.03) and rapid decline in e-GFR (OR 1.37, CI 1.07–1.75) were both significantly associated with fasting plasma glucose. Similar result of the association of rapid decline in e-GFR with fasting plasma glucose was obtained in the diabetes (full adjustment, OR 1.57, CI 1.05–2.34). Conclusions: In the community-dwelling elderly Chinese, the average decline in e-GFR was 0.104 ml/min/1.73m2 per year, and renal functional impairment was significantly associated with hyperglycemia in the old Chinese. Figure. No caption available.

COMPARISON OF ARTERIAL STIFFNESS PARAMETERS IN HYPERTENSIVE AND TYPE-2 DIABETIC PATIENTS: THE NORTHERN SHANGHAI STUDY

Objective: Both hypertension and diabetes are powerful risk factors of cardiovascular disease, however, their contribution to arterial stiffness is different. This study was designed to compare different arterial stiffness parameters among hypertensive and type-2 diabetic patients in a community-based elderly cohort. Design and method: 2,098 (aged 70.3 ± 5.6 years) participants were recruited till June 2017. All participants were divided into 4 groups: I. without hypertension and without diabetes (normal group), II. without hypertension and with diabetes (DM group), III. with hypertension and without diabetes(HTN group), and IV. with hypertension and with diabetes (DM+HTN group). Three arterial stiffness parameters were measured with validated devices, including carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), and pulse pressure amplification (PPA). Results: The body mass index (BMI) was significantly lower in normal group than in the other 3 groups (P <  = 0.02). Mean age, current smoker rate, physical activity, and education level were similar among 4 groups (P> = 0.22). Spearman correlation analysis showed that arterial stiffness parameters significantly correlated with age, mean blood pressure and heart rate. Generalized linear model with Tukey adjustment was applied to pairwise compare arterial stiffness parameters. Potential confounders including age, gender, BMI, mean blood pressure, heart rate, LDL-C, and use of insulin were adjusted in the model. Compared with normal group, PWV in the other 3 groups were significantly higher (P < 0.01), and PWV in DM+HTN group was significantly higher than DM group and HTN group (P < 0.001). The AIx in DM group and in DM+HTN group were significantly lower than in normal group (P < 0.001), while AIx in HTN group and normal group were similar (P = 0.49). As for PPA, they did not differ between participants with diabetes and without diabetes (with/without hypertension, P = 0.99 and P = 0.12, respectively), while PPA in patients with hypertension were significantly higher than those without hypertension (P < 0.001). Figure. No caption available. Conclusions: In the community-based elderly cohort, PWV is associated with both DM and HTN. AIx is associated with DM but not HTN, and PPA is associated with HTN but not DM. This result may improve the cardiovascular risk assessment in the future.

Comparison of pulse wave velocity and pulse pressure amplification in association with target organ damage in community-dwelling elderly: The Northern Shanghai Study

This study aimed to investigate the discrepancy between pulse wave velocity (PWV) and pulse pressure amplification (PPA) in association with hypertensive target organ damage (TOD) in the elderly. From June 2014 to August 2015, 1599 participants aged >65 years old from communities located in northern Shanghai were recruited. Carotid-femoral pulse wave velocity (cfPWV), peripheral blood pressure (BP), central BP and other TOD indicators, including the ratio of the early ventricular filling velocity (E) to the peak velocity of the tissue Doppler velocity of septal mitral annulus (E/Ea), left ventricular mass index (LVMI), carotid intima-medium thickness (CIMT), estimated glomerular filtration rate (eGFR), and urinary albumin–creatinine ratio (ACR), were determined for each participant. PPA was defined as the peripheral-to-central pulse pressure ratio. In multivariable linear regression analysis, cfPWV was significantly associated with CIMT (β = 12.83 ± 4.28 μm per SD; P = 0.003) and eGFR (β = −1.85 ± 0.69 ml/min/1.73 m2 per SD; P = 0.007), whereas PPA was significantly associated with E/Ea (β = −0.25 ± 0.10 per SD; P = 0.01) and LVMI (β = −3.00 ± 0.78 g/m2 per SD; P < 0.001). Similarly, in multivariable logistic regression analysis, cfPWV was significantly associated with arterial plaque (odds ratio [OR], 1.21 [95% confidence interval [CI], 1.05–1.39]; P = 0.007), peripheral artery disease (OR, 1.22 [95% CI, 1.06–1.42]; P = 0.007), chronic kidney diseases (OR, 1.24 [95% CI, 1.01–1.54]; P = 0.04) and microalbuminuria (OR, 1.21 [95% CI, 1.07–1.37]; P = 0.002), while PPA was tightly associated with left ventricular hypertrophy (OR, 0.85 [95% CI, 0.72–0.99]; P = 0.04) and diastolic dysfunction (OR, 0.78 [95% CI, 0.64–0.96]; P = 0.02). In conclusion, cfPWV is a vessel-related and renal-related biomarker, while PPA is a cardiac-related biomarker in community-based elderly.

Association of asymptomatic target organ damage with secreted frizzled related protein 5 in the elderly: the Northern Shanghai Study

Objective Secreted frizzled related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that is implicated in metabolic and cardiovascular disease (CVD). However, little is known about the relevance of SFRP5 with asymptomatic hypertensive target organ damages (TODs). We aimed to investigate the association between SFRP5 and TOD in a large population. Clinical trial registration NCT02368938. Methods A total of 1,745 community-dwelling elderly subjects aged over 65 years from northern Shanghai were recruited in the study. Plasma SFRP5 level was measured by an enzyme-linked immunosorbent assay. Asymptomatic TODs, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity, carotid intima–media thickness (CIMT), pulse wave velocity (PWV), estimated glomerular filtration rate, and urinary albumin–creatinine ratio were evaluated. Results Plasma SFRP5 level was negatively associated with body mass index, waist/hip ratio, and fasting blood glucose (all P<0.001). Men, compared with women, had lower plasma SFRP5 level (4.19 vs 5.13 ng/mL, P<0.001). Additionally, plasma SFRP5 level was lower in diabetics than in those without diabetes (4.30 vs 4.81 ng/mL, P<0.05). Furthermore, an inverse association was observed between SFRP5 and PWV and CIMT (both P<0.05). Lastly, the multivariate logistic regression analysis showed lower SFRP5 level was significantly associated with increased arterial stiffness in the elderly (odds ratio 0.83, 95% confidence interval 0.71 to 0.99 per 1 standard deviation increase, P<0.05). Conclusion Plasma SFRP5 level was inversely correlated with conventional cardiovascular risk factors, and low plasma SFRP5 was also significantly associated with arterial stiffening in the elderly Chinese population.

[PP.17.03] EGFRS FROM ASIAN AND CHINESE MODIFIED CKD-EPI EQUATIONS WERE ASSOCIATED BETTER WITH TARGET ORGAN DAMAGES IN COMMUNITY-DWELLING CHINESE ELDERLY: THE NORTHERN SHANGHAI STUDY

Objective: In literature, many equations exist in assessing patients’ eGFR, but those equations were mainly derived and validated in the population from the western countries. Therefore, the efficacy of those equations in the Chinese population remains unclear, as well as their comparison. Since the eGFR decline is a frequent manifestation in elderly and is strongly associated with other target organ damages (TODs), we aimed to investigate whether the recent eGFRs equations derived from Asian and Chinese are better associated with TODs than other equations in the Chinese elderly. Figure. No caption available. Design and method: 1599 community-dwelling elderly subjects (age>65 years) in northern Shanghai were recruited from June 2014 to August 2015. Hypertensive TODs were assessed for each participant, including left ventricular mass index, carotid-femoral pulse wave velocity, carotid intima-media thickness (IMT), ankle-brachial index and urine albumin to creatinine ratio. Participants’ eGFRs were calculated from the MDRD, CKD-EPI, Chinese abbreviated MDRD, Asian modified CKD-EPI (aCKD-EPI) equation and Chinese modified CKD-EPI (cCKD-EPI) equation, respectively. Results: multivariate regression analysis, only eGFRs from aCKD-EPI and cCKD-EPI equations were significantly and inversely associated with carotid IMT (p = 0.004 and p = 0.049, respectively). In logistic models, after confounders were adjusted, decreased eGFR from all the equations were significantly associated with lower ABI (p < 0.001), micro-albuminuria (p < 0.001) and increased PWV (p < 0.001). Only decreased eGFRs from aCKD-EPI and cCKD-EPI equations were significantly associated with increased IMT (both crude p < 0.05). In the ROC analysis, only aCKD-EPI and cCKD-EPI equations presented significant associations with all the listed hypertensive TODs (p value from p < 0.05 to p < 0.001). Conclusions: In the Chinese elderly, eGFRs from aCKD-EPI or cCKD-EPI equations are better associated with hypertensive TODs, as compared with other eGFR equations.