Changes in pulse pressure × heart rate, hs-CRP, and arterial stiffness progression in the Chinese general population: a cohort study involving 3978 employees of the Kailuan Company.

BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness, which represents sub-clinical atherosclerosis. Pulsatile stress and high-sensitivity C-reactive protein (hs-CRP) are associated with arteriosclerosis. However, there is no prospective data confirming whether changes in pulsatile stress and inflammatory markers affect the progression of arterial stiffness. The aim of this study was to investigate the relationships over time between the effects of changes in pulsatile stress and hs-CRP, and arterial stiffness progression during a 2-year follow-up. METHODS: We performed a longitudinal study involving 3978 participants. All participants underwent a physical examination in 2010-2011 and 2012-2013, during which we measured participants' hs-CRP levels, brachial-ankle pulse wave velocity (baPWV), and pulsatile stress. RESULTS: Baseline hs-CRP was correlated with baPWV (r = 0.18, P = 0.000); however the correlation was weaker than that with systolic blood pressure (r = 0.65), pulsatile stress (r = 0.57), and rate-pressure product (r = 0.58). Multiple linear regression analysis demonstrated that changes in pulsatile stress, mean arterial pressure, and low-density lipoprotein-C (LDL-C) were positively correlated with changes in baPWV, with correlation coefficients of 0.27, 0.25, and 0.07, respectively, but not with changes in hs-CRP. Moreover, each 100-aU increase in pulsatile stress, 1 mmHg increase in mean blood pressure, and 1 mmol/L increase in LDL-C was associated with a 3 cm/s, 4.78 cm/s, and 17.37 cm/s increase in baPWV, respectively. CONCLUSIONS: Pulsatile stress increases are associated with arterial stiffness progression, but that changes in hs-CRP had no effect on arterial stiffness progression. Hs-CRP may simply be a marker of inflammation in arterial stiffness and has no association with arterial stiffness progression.

Correlation between the trajectory of systolic blood pressure and new renal damage in a nonhypertensive population.

OBJECTIVE: This study aims to investigate the correlation between the trajectory of systolic blood pressure (SBP) and new renal damage in a nonhypertensive population. PATIENTS AND METHODS: This prospective cohort study included a total of 14 382 nonhypertensive individuals, employees of Kailuan Group of Companies, who took part in five healthy examinations in 2006-2007, 2008-2009, 2010-2011, 2012-2013, and 2014-2015, and had complete data. These individuals were divided into four groups according to the different trajectories of SBP: low-low, low-stable, middle-high, and high-high groups. The correlation between the trajectory of SBP and new renal damage in a nonhypertensive population was analyzed using a multivariate Cox's proportional hazard regression model. RESULTS: (a) A total of 14 382 individuals had complete data and the average age of these individuals was 44.6±10.8 years. Among these, 10 888 (75.7%) individuals were men and 3494 (24.3%) individuals were women. (b) These individuals were divided into four groups according to different trajectories of blood pressure: low-low group, accounting for 13.15% (blood pressure was <106 mmHg); low-stable group, accounting for 53.91% (blood pressure was between 115 and 116 mmHg); middle-high group, accounting for 28.77% (blood pressure was between 125 and 131 mmHg); and high-high group, accounting for 4.6% (blood pressure was between 126 and 151 mmHg). (c) With the increase in the trajectory of SBP, the detection rate of renal damage increased gradually. From the low-low group to the high-high group, the detection rates of estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m were 2.3, 2.4, 3.6, and 4.3%, respectively; the positive rates of urinary protein were 1.7, 2.9, 3.8, and 5.5%, respectively; and the detection rates of eGFR less than 60 ml/min/1.73 m or positive urinary protein were 4, 5.2, 7.3, and 9.3%, respectively (P<0.05). (d) After adjustment for other confounding factors, multivariate Cox's proportional hazard regression analysis showed that compared with the low-low group, the risk of eGFR less than 60 ml/min/1.73 m increased by nearly 1.5 times in the high-high group and in the low-stable, middle-high, and high-high groups, the risks of positive urinary protein, eGFR less than 60 ml/min/1.73 m, or positive urinary protein increased by 1.48-2.34 and 1.20-1.70 times, respectively. CONCLUSION: In a nonhypertensive population, the high trajectory of SBP is a risk factor for kidney damage.

Time-cumulated blood pressure exposure and incident impairment of glucose tolerance and diabetes mellitus.

BACKGROUND: With the marked increase in the prevalence of diabetes mellitus, it was the purpose of our study to assess a potential association of time-cumulated exposure to systolic (CumSBP) and of diastolic blood pressure (CumDBP) with onset of impaired glucose tolerance and diabetes mellitus. METHODS: The prospective investigation included participants of the longitudinal Kailuan Study with three baseline examinations in 2006-2007, 2008-2009 and 2010-2011, re-examination in 2012-2013, and no diabetes mellitus at baseline. Cumulative blood pressure (BP) was calculated as cumBP = [(BP1 + BP2)/2 × time1-2] + [(BP2 + BP3)/2 × time2-3]. Based on cumSBP, the study population was stratified into four groups (cumSBP < 480mmHgxyear;n = 15,339; 480mmHgxyear ≤ cumSBP < 520mmHgxyear;n = 7214; 520mmHgxyears ≤ cumSBP < 560mmHgxyears;n = 5675; and cumSBP ≥ 560mmHgxyears;n = 10,576). RESULTS: After adjusting for demographic, anthropomorphic, biochemical, socioeconomic and lifestyle parameters and as compared with the first group, the second, third and fourth group showed a significantly higher incidence of diabetes (P-trend < 0.001;hazard ratio (HR);95% confidence interval (CI):1.28(1.08,1.51),1.54(1.29,1.84), and 2.33(1.98,2.73), respectively), higher incidence of impairment of glucose tolerance (P-trend < 0.001;HR;95% CI1.17(1.02,1.33), 1.43(1.25,1.64), and 2.09(1.85,2.37), respectively), and higher incidence of diabetes developing out of an impairment of glucose tolerance (P-trend < 0.001;HR;95% CI:1.22(0.97,1.54),1.47(1.16,1.86), and 2.01(1.62,2.50), respectively). An increase in cumSBP by 10 mmHg/year or an increase in cumDBP by 5 mmHg/year was associated with a hazard ratio of incident diabetes of 1.04 (95% CI:1.03,1.04) and 1.02(1.02,1.03), respectively, with a hazard ratio of incident impairment of glucose tolerance of 1.04(95% CI:1.03,1.04) and 1.03(95% CI:1.02,1.03), respectively, and with a hazard ratio of incident diabetes developing from impairment of glucose tolerance of 1.04(95% CI:1.03,1.04) and 1.03(95% CI:1.02,1.03), respectively. CONCLUSIONS: Time-cumulated exposure to elevated blood pressure was significantly associated with an elevated incidence of impaired glucose tolerance and diabetes.

Ideal cardiovascular health score and incident end-stage renal disease in a community-based longitudinal cohort study: the Kailuan Study.

OBJECTIVES: To investigate an association between ideal cardiovascular health metrics (CVH) and the risk of developing end-stage renal disease (ESRD). SETTING: Community of Kailuan in Tangshan/China. PARTICIPANTS: We examined in a community-based longitudinal cohort study 91 443 participants without history of stroke or myocardial infarction at baseline in 2006-2007, with a glomerular filtration rate (GFR) ≥15 mL/min at baseline, and who participated in at least 1 of 3 follow-up examinations in 2008-2009, 2010-2011 and 2012-2013. INTERVENTIONS: CVH was measured by 7 key health factors (smoking, body mass index, physical activity, healthy dietary score, total cholesterol blood concentration, blood pressure, fasting blood glucose) each of which ranged between 'ideal' (2) and 'poor' (0). With a maximal CVH score of 14, the study participants were divided into categories of <5, 5-9 and 10-14 points. PRIMARY AND SECONDARY OUTCOME MEASURES: CHV, incidence of ESRD. RESULTS: Incidence of ESRD ranged from 7.06‰ in the lowest CVH category to 2.34‰ in the highest CVH category. After adjusting for age, sex, educational level, income, alcohol consumption and GFR, the lowest CVH category as compared with the highest CVH category had a significantly higher risk of incident ESRD (adjusted HR 2.87; 95% CI 1.53 to 5.39). For every decrease in group number of the cum-CVH score, the risk of ESRD increased by 20% (HR 1.20; 95% CI 1.13 to 1.28). The effect was consistent across sex and all age groups. CONCLUSIONS: A low CVH score significantly increased the risk of incident ESRD. Risk factors for cardiovascular events may also be associated with an increased risk for kidney failure.

The ideal cardiovascular health metrics associated inversely with mortality from all causes and from cardiovascular diseases among adults in a Northern Chinese industrial city.

BACKGROUND AND AIMS: The American Heart Association has recently established seven ideal cardiovascular health metrics for cardiovascular health promotion and disease reduction (i.e., non-smoking, normal body mass index, physically active, healthy diet, and normal levels of cholesterol, blood pressure and fasting blood glucose). The present study seeks to evaluate how well these metrics predict mortality from all causes and cardiovascular diseases in adult Chinese living in a northern industrial city. METHODS AND RESULTS: Data of 95,429 adults who participated in the Kailuan cohort study from June 2006 to October 2007 was analyzed. All participants underwent questionnaire assessment, clinical examination, laboratory assessments and were followed up biannually. During a median follow-up of 4.02 years, 1,843 deaths occurred, with 597 deaths resulting from cardiovascular diseases. Lower mortality rates from all causes and cardiovascular diseases were observed among the subjects who met a higher number of the ideal health metrics. Compared to the participants who met none or one ideal health metric, those meeting ≥5 ideal health metrics had a lower risk of all-cause mortality by 30% (adjusted hazard ratio, 0.70; 95% confidence interval, 0.56-0.88) and a lower risk of mortality from cardiovascular diseases by 39% (adjusted hazard ratio, 0.61; 95% confidence interval, 0.41-0.89) . Four metrics (smoking status, physical activity, blood pressure and fasting blood glucose) were significantly associated with all-cause mortality. Three metrics (physical activity, blood pressure and fasting blood glucose) were significantly associated with mortality from cardiovascular diseases. CONCLUSION: The number of ideal health metrics is negatively associated with mortality rates from all causes and cardiovascular diseases among adults in a Northern Chinese industrial city. The data supports the AHA recommendation of ideal health metrics for adults from Northern China.

[History of pregnancy induced hypertension is linked with increased risk of cardio-cerebral vascular events].

OBJECTIVE: To compare the incidence of cardio-cerebral vascular events between pregnancy induced hypertension (PIH) women and non-PIH(NPIH) women. METHODS: Ambispective cohort study method was used and 4630 pregnant women giving birth during October 1976 to December 2008 in our hospital and participated the healthy examination between July 2006 and October 2007 at Kailuan medical group were included and divided into PIH group (n = 694) and NPIH group (n = 3936) by the history of PIH. Incidence of cardio-cerebral vascular events (myocardial infarction, cerebral infarction and cerebral hemorrhage) was obtained during follow-up. Multivariable Cox proportional hazards regression models was used to assess the relative risk of cardio-cerebral vascular events. RESULTS: (1) The follow-up time was 2 to 34 (15.32 ± 7.94) years. (2) The childbearing age, systolic blood pressure and diastolic blood pressure before delivery were significantly higher while gestational weeks and weight of newborn were significantly less in PIH group than in NPIH group (all P < 0.01). Levels of systolic blood pressure, diastolic blood pressure, waist circumference, body mass index, triglyceride, total cholesterol and fasting blood glucose during healthy examination between July 2006 and October 2007 were significantly higher in PIH group than in NPIH group (P < 0.05 or P < 0.01). (3) There were 71 cardio-cerebral vascular events during the follow-up. In PIH group, the incidence rate of cardio-cerebral vascular events, myocardial infarction and cerebral infarction was 20.64%, 11.08% and 8.67%, respectively, while the corresponding incidence rate was 7.82%, 4.02% and 2.67% in NPIH group (all P < 0.01). After adjustment for other traditional cardiovascular risk factors, the risk of total cardio-cerebral vascular events, myocardial infarction and cerebral infarction in PIH group was 2.99 fold (95%CI: 1.80 - 4.95), 3.91 fold (95%CI: 1.71 - 8.91) and 3.96 fold (95%CI: 1.95 - 8.05) higher than in NPIH group. CONCLUSION: PIH is an independent risk factor for cardio-cerebral vascular events.

[The prevalence and distribution of ideal cardiovascular health behavior in employees of Kailuan Group cohort].

OBJECTIVE: To observe the prevalence and distribution of ideal cardiovascular health behavior. METHODS: Health examination data between 2008 to 2009 from the employees of Kailuan Group were analyzed. RESULTS: A total of 101 333 subjects took part in the health examination, subjects with previous myocardial infarction (n = 871), stroke (n = 2255), myocardial infarction and stroke (n = 162) and subjects with incomplete examination data (n = 9311) were excluded and 88 534 subjects were included for final analysis [mean age (50.6 ± 12.3) years, male 69 916]. (1) Body mass index (BMI), systolic and diastolic pressure, cholesterol (TC) and triglyceride were significantly higher in males than in females (all P < 0.05), women's income and the education lever were significantly higher than men (P < 0.05). (2) The distribution of ideal cardiovascular health behavior (smoking, BMI, physical exercise, salt intake) was 55.8%, 41.4%, 18.9% and 14.0% respectively among the population; the ideal cardiovascular factors (fasting blood glucose, TC, blood pressure) was 80.9%, 61.8% and 18.5%, respectively. (3) The subjects with distribution of seven, six, five, four ideal cardiovascular health behavior and factors was 0.1%, 1.9%, 9.1%, 20.3%, respectively. (4) Multiple logistic regression analysis showed that female, age < 55 and high education level were associated with the ideal cardiovascular health status with a RR value (95%CI) of 4.52 (4.32 - 4.72), 1.46 (1.39 - 1.53) and 2.23 (2.10 - 2.37), respectively. CONCLUSION: The prevalence of ideal cardiovascular health is extremely low in the study population, most persons were not in the ideal cardiovascular health behavior and factors and female, age < 55 and high education level are linked with ideal cardiovascular health status.

[Impact of ideal health behaviors and health factors on the detection rate of the carotid plaques].

OBJECTIVE: To explore the impact of ideal health behaviors and health factors on the detection rate of the carotid plaques. METHODS: Subjects with previous stroke, TIA, myocardial infarction were excluded from the study. A total of 5852 employees (active and retired employers from Tangshan Kailuan company) aged 40 years and over were included through stratified random sampling. Information was obtained from the unified questionnaire, measurements of blood biochemistry and carotid artery ultrasonography. RESULTS: (1) The carotid artery plaque detection rates were 67.0%, 52.3%, 50.5%, 44.3%, 37.2%, 31.9%, 26.1% and 4.2% in the groups with 0, 1, 2, 3, 4, 5, 6 and 7 components of ideal cardiovascular health behaviors and health factors, respectively. (2) The carotid artery plaques total burden score [TBS: M (Q1, Q3)] were 7(7,7), 7(5,7), 7(5,7), 5(3,5), 5(3,5), 5(3,5), 3(3,3), 3(3,3) in the groups with 0, 1, 2, 3, 4, 5, 6 and 7 components of ideal cardiovascular health behaviors and health factors, respectively. (3) Multiple logistic regression analysis showed that 3, 4, 5 and greater than 5 components of ideal cardiovascular health behaviors and health factors were protective factors against carotid plaques compared to less than 2 components of ideal cardiovascular health behaviors and factors (all P < 0.05), the OR (95%CI) values were 0.78 (0.62 - 0.98), 0.53(0.62 - 0.98), 0.52 (0.39 - 0.71) and 0.40 (0.25 - 0.64), respectively. CONCLUSION: Increasing ideal cardiovascular health behaviors and factors are negatively linked with the detection rate and TBS of the carotid plaques.

[Association between baseline high sensitivity C-reactive protein level and the first cardio-cerebral vascular event in diabetic population: a prospective cohort study].

OBJECTIVE: To evaluate the predictive value of baseline serum high sensitivity C-reactive protein for the first cardio-cerebral vascular event in the population with diabetes. METHOD: In this prospective cohort study, a total of 101 510 employees of Kai Luan Group, who received healthy examination from July 2006 to October 2007, were screened and 7865 subjects with fasting plasma glucose ≥ 7.0 mmol/L or known diabetes mellitus and under insulin or hypoglycemic drugs therapy were followed up for 38 - 53 (48.02 ± 3.14) months. RESULTS: (1) Incidence rates of total cardio-cerebral vascular events, cerebral infarction and myocardial infarction increased in proportion to increased levels of baseline hsCRP (P < 0.01). After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and cigarette smoking, multivariate Cox's proportional hazards regression analysis indicated that the individuals in the highest quartile of hsCRP levels group (hsCRP ≥ 2.50 mg/L) had an increased risk of total cardio-cerebral vascular events (RR: 1.64, 95% CI: 1.20 - 2.24), cerebral infarction (RR: 1.52, 95% CI: 1.03 - 2.24), myocardial infarction (RR: 2.57, 95% CI: 1.34 - 4.91) compared with those in the lowest quartile group (hsCRP < 0.41 mg/L). (2) Higher baseline hsCRP levels were associated with aging, female gender, higher BMI, SBP, DBP, fasting blood glucose, TC, TG, LDL-C levels and lower HDL-C levels (all P < 0.05). CONCLUSION: Baseline hsCRP level is associated with increased first cardio-cerebral vascular event in the population with diabetes.

Downregulation of glucocorticoid receptors of liver cytosols and the role of the inflammatory cytokines in pathological stress in scalded rats.

Preliminary experiments indicated that target cells were resistant to glucocorticoid (GC) after pathological stress. This study was designed to investigate the alterations in plasma corticosterone level and GC receptor (GR) of liver cytosols, to assess the relative inflammatory cytokines contribution to GC resistant, and to observe the action of alpha-melanocyte-stimulating hormone (alpha-MSH) on the potential implications of glucocorticord regulatory effects in burned rats. Male Wistar rats (weight range, 180-200g) received a 35% total body surface area immersion scald and were randomly divided to receive either tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), polyclonal antibody (pAb), alpha-MSH, Ac-D-Lys-L-Pro-D-Val (KPV peptide), or saline (control). The binding capacity (Rt) of the steroid-binding sites was measured by radioligand binding assay, using [3H]dexamethasone as the ligand. We examined plasma levels of IL-1beta, TNFalpha, IL-10, and corticosterone following scald challenge in rats. The Rt of GR (208.45+/-30.78fmol/mg of protein) in hepatic cytosol in rats, 12h later the scald was significantly lower than that (306.71+/-27.96fmol/mg of protein) of the control group (P<0.01). The injections of anti-rat TNFalpha (257.80+/-12.82fmol/mg of protein), IL-1beta antibody (254.46+/-21.21fmol/mg of protein), alpha-melanocyte-stimulating hormone (278.32+/-7.76fmol/mg of protein) and KPV peptide (263.46+/-17.46fmol/mg of protein) might prevent the Rt of GR from decreasing in hepatic cytosols of rats with scald, respectively (all of P<0.05) in vivo. Scald-induced robust increases in plasma IL-1beta (214.08+/-27.25pg/ml), TNFalpha (111.18+/-23.97pg/ml), IL-10 (177.50+/-15.79pg/ml) and corticosterone (2680+/-443.23ng/ml) levels after 12h. The administration of TNFalpha, IL-1beta pAb, alpha-MSH and KPV might attenuate these increases. These studies suggest that pro-inflammatory cytokines are involved in downregulation of GRs and thus alpha-MSH and KPV might increase the level of GR in rats with immersion scald.

Changes in glucocorticoid and mineralocorticoid receptors of liver and kidney cytosols after pathologic stress and its regulation in rats.

OBJECTIVE: As effectors, glucocorticoid and mineralocorticoid receptors play an important role in pathologic stress. This study was designed to observe the changes in glucocorticoid receptor of liver cytosols and mineralocorticoid receptor of kidney cytosols after pathologic stress in rats. DESIGN: Controlled laboratory study. SETTING: Medical university. SUBJECTS: Male Wistar rats (weight range, 180-200 g). INTERVENTIONS: Rats received a low-degree or heavy-degree immersion scald that covered 10% or 35% total body surface area and were randomly divided to receive either tumor necrosis factor-alpha, interleukin-1beta polyclonal neutralizing antibody, alpha-melanocyte-stimulating hormone, KPV peptide (Ac-D-Lys-L-Pro-D-Val), or saline (control). The binding capacity and the apparent dissociation constant of the steroid-binding sites of normal, low-degree, and heavy-degree scalded rats were measured by radioligand-binding assay, with [3H]dexamethasone and aldosterone as the ligand, respectively. MEASUREMENTS AND MAIN RESULTS: The binding capacity of glucocorticoid receptor in hepatic cytosols in rats 12 hrs after heavy-degree scald (208.45 +/- 30.78 fmol/mg of protein) was lower than that of the control group (306.71 +/- 27.96 fmol/mg of protein; p < .01). The binding capacity of glucocorticoid receptor in hepatic cytosols in rats 12 hrs after low-degree scald (296.64 +/- 16.06 fmol/mg of protein) was not significantly different compared with the control group (p > .05). There were two types of mineralocorticoid receptor in kidney cytosols in rats, and their binding capacity and apparent dissociation constant were not identical. The binding capacity of mineralocorticoid receptor in rats 12 hrs after heavy-degree scald (binding capacity 1, 22.40 +/- 5.40 fmol/mg of protein; binding capacity 2, 196.30 +/- 32.50 fmol/mg of protein) was lower than that of the control group (binding capacity 1, 41.60 +/- 7.20 fmol/mg of protein; binding capacity 2, 317.60 +/- 70.00 fmol/mg of protein; p < .01). The binding capacity of mineralocorticoid receptor in kidney cytosols in rats 12 hrs after low-degree scald (binding capacity 1, 41.40 +/- 5.00 fmol/mg of protein; binding capacity 2, 314.80 +/- 45.70 fmol/mg of protein) was not significantly different compared with the control group (p > .05). The injections of anti-rat tumor necrosis factor-alpha, interleukin-1beta polyclonal neutralizing antibody, alpha-melanocyte-stimulating hormone, and KPV peptide (Ac-D-Lys-L-Pro-D-Val) might prevent a reduction in the binding capacity of glucocorticoid receptor in hepatic cytosols and mineralocorticoid receptor in kidney cytosols in rats with heavy-degree scald in vivo. CONCLUSIONS: These studies suggest that the glucocorticoid receptor of hepatic cytosols and the mineralocorticoid receptor of renal cytosols decreased in rats with heavy-degree immersion scald and that the injections of anti-rat tumor necrosis factor-alpha, interleukin-1beta polyclonal neutralizing antibody, alpha-melanocyte-stimulating hormone, and KPV peptide might increase the level of glucocorticoid receptor and mineralocorticoid receptor in vivo.