The relevance of mental and physical sub-health status

Abstracts

Objective: Augmentation in intracellular Ca2+ is thought to be critically involved in hypertension and cardiac dysfunction. Transient receptor potential canonical (TRPC) channels are cation-selective influx channels that can initiate cardiac hypertrophy when overexpressed because of increased Ca2+ influx. There is evidence that myocardial fibrosis and inflammatory are positively correlated. Our hypothesis is that high dietary salt can induce TRPC6-mediated Ca2+ influx for proper activation of nuclear factor κB, which increases inflammatory reaction, which leads to myocardial fibrosis. Methods: Wistar rats were assigned randomly to receive 8% high salt (HS groups, n = 15) and 0.5% normal salt (NS group, n = 15) for 23 weeks. Tail-cuff blood pressure was measured every two weeks. The myocardial cell diameter (MCD) and interstitial collagen depositions were measured by HE and Masson staining respectively. Expressions of TRPC6, NF-κB, TNF-α, IL-1β and TGF-β1 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and by western blot analysis. Results: High-salt diet caused marked hypertension, cardiac hypertrophy and fibrosis. RT-PCR and western blot revealed that HS group had enhanced heart TRPC6 and NF-κB p65, as well as increased heart levels of proinflammatory cytokines and growth factors (TNF-α, IL-1β and TGF-β1) compared with NS group. Conclusions: These results suggest that inflammation is exacerbated in fibrotic heart induced by high salt when TRPC6 expression elevated, indicating that TRPC6 may act as a potential regulator of the inflammatory process to cardiac fibrosis in Wistar rats. doi:10.1016/j.ijcard.2011.08.775

Pharmacogenetics 0252 Influence of rAAV1 mediated beta1-adrenergic receptor gene overexpression on metoprolol antihypertensive effect of spontaneously hypertensive rats HONG YUANa,d, MEIZHEN ZHANGb, ZHIJUN HUANGa, XIAOWEI XINGc, GUOPIN YANGa, XIAOHONG TANGd a The Center of Clinical Pharmacology of the Third Xiangya Hospital, Central South University, Changsha, China b Clinical Pharmacology Research, Central South University, Changsha, China c Department of Center for Medical Experiments, Third Xiangya Hospital of Central South University, Changsha, China d Department of Cardiology, Third Xiangya Hospital of Central South University, Changsha, China Objective: We investigated the influence of rAAV1 mediated beta1adrenergic receptor gene overexpression on metoprolol antihypertensive effect of spontaneously hypertensive rats. Methods: 1. Randomly taking out six spontaneously hypertensive rats (SHRs) as rAAV1/CMVEGFP group, others were randomly divided into 3 groups: rAAV1/CMVAdrb1+ metoprolol Group (n= 6), surgical + metoprolol group (n = 6) and surgical + saline group (n = 6). All of them were measured blood pressure (BP) by weekly and adjusted the dose of metoprolol according to their weight. Four weeks later SHRs were killed. 2. Reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RTPCR were used to assay mRNA expression of beta1-AR gene, protein expression of beta1-AR were analyzed by immunohistochemistry and western blot. Results: 1. Expression of beta1-AR gene in each group: RTPCR and real-time RT-PCR results showed that rAAV1/CMV-Adrb1 injection significantly increase beta1-AR mRNA expression in myocardial tissue of SHRs (0.587 ± 0.132 vs 0.212 ± 0.075, P b 0.05). Immunohistochemistry and western blot results demonstrated that rAAV1/CMVAdrb1 injection could significantly increase the expression of beta1-AR protein in myocardial tissue of SHRs (0.545 ± 0.119 vs 0.421 ± 0.136, P b 0.05). 2. Antihypertensive effects of each group: After 4 weeks of intervention, systolic BP was significantly lower in the rAAV1/CMV-

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Adrb1 + metoprolol group and the surgical + metoprolol group than that in the saline group (176.2 ± 8.5 mm Hg vs 182.5 ± 4.5 mm Hg vs 198.7± 7.0 mm Hg, P b 0.05). The reduction of systolic BP was significantly higher than in the rAAV1/CMV-Adrb1 + metoprolol group than that in the sham group (27.8 ± 8.5 mm Hg vs 16.8 ± 2.5 mm Hg, P b 0.05). Conclusions: 1. The rAAV1/CMV-Adrb1 can significantly increase the expression of beta1-AR in myocardial of SHRs. 2. The SHRs whose beta1-AR gene is overexpressed may have better antihypertensive response to metoprolol and it may be one of the reasons for influencing the individual antihypertensive response of metoprolol. doi:10.1016/j.ijcard.2011.08.776 0355 Assessing the genetic impacts of 144 candidate polymorphisms on the low-density lipoprotein cholesterol lowering efficacy of atorvastatin in Han Chinese YUE QI, JING LIU, WEI WANG, YAN LI, JUN LIU, JIAYI SUN, MIAO WANG, DONG ZHAO Department of Epidemiology, Capital Medical University Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China Objective: We aimed to assess the influence of candidate genetic variation on statin efficacy in a cardiovascular disease (CVD)-high-risk Chinese population to elucidate the inherited genetic underpinnings, which would further direct the statin therapy and thus the CVD prevention. Methods: This study included 318 patients aged 20–70 years based on the standards of statin administration. All patients were treated with atorvastatin at a dosage of 20 mg daily for 4 weeks. Lipid-relevant indexes were measured before/after administration. Total 144 common polymorphisms harboring 17 candidate genes related to statin or lipids metabolism were genotyped by the Illumina gene microarray method. Results: ATP-binding cassette, subfamily B, member1 (ABCB1) gene rs2235013, rs1128503, rs10276036 and ATP-binding cassette subfamily C member2 (ABCC2) gene rs717620 were individually and significantly associated with the percentage reduction in low-density lipoprotein cholesterol (LDL-C). The strength of associations between rs717620 CNT, rs1128053 TNC polymorphisms and LDL-C reduction remained even after adjustment for other CVD-relevant risk factors. Under the dominant genetic mode, carriers of rs717620 T allele conferred 1.85-times higher LDL-C response [odds ratio (OR)=1.85; 95% confidence interval (95% CI): 1.11–3.08], than those with CC genotype after multivariate adjustment. While under the recessive model, rs1128053 CC genotype had 60% lower LDL-C response (OR=0.40; 95% CI=0.17–0.95; P=0.037) than T allele. Haplotype rs717620 T and rs1128503 T alleles had remarkable predominance in increasing LDL-C response (OR=2.00; 95% CI: 1.22–3.32; P=0.006). Multivariate regression analysis showed that rs717620 and rs1128503 together explained 23% of percentage change in LDL-C in response to atorvastatin. Conclusions: This study lent some credence to the fact that statin excretion relevant genes ABCB1 and ABCC2 might be potential candidates for atorvastatin lowering lipids in CVD-high-risk Chinese, which was further strengthened by our conjoint analysis of these two genes. doi:10.1016/j.ijcard.2011.08.777

Psychosocial Factors 0304 The relevance of mental and physical sub-health status NINGLING SUN, LUYAN WANG PeKing University People's Hospital, Beijing, China

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Abstracts

Objective: WHO defined health in a way as ‘physical, mental and social well-being’. Now it is well known that physical illness can induce a mental disorder. Is there any relevance between physical and mental sub-health status? Do they influence each other, and which one is more important? Our hypothesis was that mental subhealth might interact with physical sub-health. Our objectives were (1) to find psychological characteristic in physical sub-health persons, and (2) to identify the relationship between mental and physical sub-health status. Methods: We recruited 1141 subjects from community who were all received routine medical examination, including of measurement of blood pressure, waist circumference, body weight, fasting plasma glucose (FPG), 2-h plasma glucose in OGTT, low-density lipoprotein cholesterol (LDL-C), liver and renal function. All the subjects were divided into three groups: (I) health group: without medical history and physical examination were normal; (II) physical sub-health group: systolic blood pressure was between 130 and 139 mm Hg, and/or diastolic blood pressure was between 85 and 89 mm Hg, and/or LDL-C was between 3.37 and 4.10 mmol/L, and/or FPG was between 6.1 and 6.9 mmol/L, and/or 2hPG 7.8 and 11.0 mmol/L; (III) illness group: with past illness history or were diagnose illness through physical examination. The mental status was assessed with the Zung anxiety scale (SAS), Zung depression scale (SDS) and chronic fatigue questionnaire. Results: Analysis shows that (1) anxiety was most common in illness group and more common in sub-health group than in health (51.75%, 39.67%, 33.9% respectively, P b 0.0001), and SAS score showed the same trend (37.45 ± 11.08 vs 38.86 ± 10.70 vs 41.14 ± 11.01, P = 0.0001); (2) incidence of depression was higher in illness and individual than health (52.38%, 44.26%, 42.32% respectively, P = 0.0245), SDS score was also higher in illness and sub-health group (41.14 ± 11.01 vs 38.86 ± 10.70 vs 37.45 ± 11.08, P = 0.0001); (3) there was no difference in chronic fatigue among three groups. If we defined anxiety or depression or chronic fatigue as mental subhealth, we found that incidence of mental sub-health status was higher in sub-health group than health (54.95% vs 51.19%, P = 0.008). Interestingly, we found waist circumference (80.12 ± 7.73 cm vs 78.02 ± 8.2 cm, P b 0.0001) and FPG (5.43 ± 0.78 mmol/L vs 5.14 ± 0.77 mmol/L, P = 0.0019) were obviously higher in sub-health subjects than in health, however SBP (119.34 ± 13.56 mm Hg vs 122.76 ± 12.71 mm Hg, P = 0.0098) and LDL-C (3.01 ± 0.65 mmol/L vs 3.23 ± 0.67 mmol/L, P b 0.0001) were lower in sub-health. Conclusion: Individuals in physical sub-health status were prone to have mental subhealth especially depression and anxiety. Mental sub-health might have some effect on impaired glycometabolism, but was not related with high-normal blood pressure and LDL-C. doi:10.1016/j.ijcard.2011.08.778

Public Health 0173 A “J-shape” association between birth weight and adult systolic blood pressure in Hong Kong Chinese women YAOJIE XIE, SUZANNE C. HO School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR Objective: Few studies have examined the effect of birth weight on adult blood pressure in Hong Kong population. We aimed: (1) to examine the association of birth weight with adult systolic blood pressure (SBP); (2) to determine whether birth weight and adult body weight interact to predict adult SBP. Methods: We studied 1253 female nurses aged 35 to 65 years old in Hong Kong. Information on birth weight, height, body weight, blood pressure and other variables

was collected by a self-administered questionnaire. The self-reported variables have been validated in a pilot study. Results: Using linear regression analysis, after adjustment for age, height, body weight, premature and salt intake, we observed a significant inverse association between birth weight and SBP (coefficient B = − 3.12, 95% CI: − 5.96 to −0.29) in birth weight b3.5 kg group, whereas a positive but no statistically significant association was found in birth weight ≥3.5 kg group (coefficient B = 2.56, 95% CI: − 2.22 to 7.34). The birth weight-SBP relationship was strengthened in overweight/ obesity (BMI ≥ 23 kg/m2, Asian standard defined by WHO) group (coefficient B = −3.70, 95% CI: −6.96 to −0.43) but disappeared in normal weight (BMI b 23 kg/m2) group (P N 0.05). No significant interaction was found between birth weight and body weight (PN 0.05). By curve estimation, we observed a quadric curvilinear association between birth weight and SBP (SBP=136.04−15.75 birth weight +2.63 birth weight2, P=0.02). Conclusions: We suggest a “J” shape association between birth weight and SBP, both lower and higher birth weight predict higher SBP. The effect of birth weight on adult systolic blood pressure is independent and amplified by overweight/obesity. doi:10.1016/j.ijcard.2011.08.779 0195 Study about the abnormal proportions of blood pressure and some metabolic indictors in the Chinese healthy check-up population LIUXIN WUa, DONGCHANG QIANGa, JIN XUb, XIAOLAN ZHAOc, LUJIANG SHIa, XIANGYANG GAOd, QIANG ZENGe a Institute of Aviation Medicine, Air Force, Beijing, China b Department of the Health Examination Center, The First Affiliated Hospital, Suzhou University, Suzhou, China c Department of the Health Examination Center, Southwest Hospital, Third Military Medical University, Chongqing, China d Xuanwu District Center for Disease Control and Prevention, Beijing, China e International Medical Center of the PLA General Hospital, Beijing, China Objective: To study the abnormal proportions of blood pressure and some metabolic indictors in the Chinese healthy check-up population. Methods: Using the nationwide healthy check-up data of 2009 collected by the healthy check-up evaluation Panel of China Health Management Association from 65 healthy check-up centers nationwide, the abnormal percentages of systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), low density lipoprotein (LDL-C), and total cholesterol (TC) were calculated. In this study, the total participants were 1,176,500 including 708,949 men and 467,551 women aged from 10 to 99. Results: With the increase of age, the proportions of isolated systolic hypertension of both genders increase; the proportions of isolated diastolic hypertension increase first and then decrease, the male gets the highest at the 50 age group while the female at the 60 age group. Both of the proportions of impaired fasting glucose and diabetes increase first and then decrease, both genders get the highest at the 70 age group. The proportions of borderline-high and high of LDL-C and TC in male go through a maximum at the 50 age group, and the female's increase from the 20 to the 60 age group but are stabilized after the 60 age group. In the 20 to the 50 age group, the male abnormal proportions of SBP, DBP and FBG are higher than those of the female at their age group. In the 20 to the 40 age group, the male borderline-high and high proportions of LDL-C and TC are higher than those of the female at their age group. Conclusions: The abnormal proportions of SBP, DBP, FBG, LDL-C and TC have gender and age differences. The males in the age of 20 to 59 are more in need to get intervention about the level of their blood pressure, FBG, LDL-C and TC. doi:10.1016/j.ijcard.2011.08.780