Increasing prevalence of hypertension in Hong Kong Cardiovascular Risk Factor Prevalence Study: role of general and central obesity

Introduction: General obesity and central obesity are well-known risk factors of hypertension. We investigated the change in the prevalence of hypertension in the population-based prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) and the relationship of change in blood pressure with change in body mass index (BMI) and waist circumference over a follow-up period of 11.9 years. Methods: A total of 2888, 1942 and 1798 subjects in CRISPS-1 (1995-1996), CRISPS-2 (2000-2004) and CRISPS-3 (2005-2008) were included in this analysis respectively. Hypertension was defined as blood pressure ≥140/90 mm Hg or taking anti-hypertensive medication. General obesity was defined as BMI ≥27.5 kg/m2 and central obesity was defined as waist circumference ≥90 cm in men or ≥80 cm in women. Results: The prevalence of hypertension increased from 18.1% to 39.4% (P<0.001 after adjusting for age and sex). The prevalence of central obesity increased from 25.4% to 41.4%, but that of general obesity decreased from 16.8% to 14.8% (both P<0.001 after adjusting for age and sex). Among 1347 subjects who did not take any anti-hypertensive medication at both CRISPS-1 and CRISPS-3, the change in waist circumference, but not that in BMI, was associated with the changes in both systolic and diastolic blood pressures (beta=0.087, P=0.015 and beta=0.122, P<0.001 respectively). Conclusions: The increase in prevalence of hypertension might be explained by the increase in central obesity. Our findings further confirm the importance of waist circumference in this population; calculating the BMI alone may give a false sense of security. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio

Association of genetic variants in gene encoding lipocalin-2 with plasma alanine aminotransferase and aspartate aminotransferase

published_or_final_versionThe 16th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 17, abstract no. 1

A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.

BackgroundRheumatoid arthritis (RA) can be divided into two major subsets based on the presence or absence of antibodies to citrullinated peptide antigens (ACPA). Until now, data from genome-wide association studies (GWAS) have only been published from ACPA-positive subsets of RA or from studies that have not separated the two subsets. The aim of the current study is to provide and compare GWAS data for both subsets.Methods and resultsGWAS using the Illumina 300K chip was performed for 774 ACPA-negative patients with RA, 1147 ACPA-positive patients with RA and 1079 controls from the Swedish population-based case-control study EIRA. Imputation was performed which allowed comparisons using 1,723,056 single nucleotide polymorphisms (SNPs). No SNP achieved genome-wide significance (2.9 × 10⁻⁸) in the comparison between ACPA-negative RA and controls. A case-case association study was then performed between ACPA-negative and ACPA-positive RA groups. The major difference in this analysis was in the HLA region where 768 HLA SNPs passed the threshold for genome-wide significance whereas additional contrasting SNPs did not reach genome-wide significance. However, one SNP close to the RPS12P4 locus in chromosome 2 reached a p value of 2 × 10⁶ and this locus can thus be considered as a tentative candidate locus for ACPA-negative RA.ConclusionsACPA-positive and ACPA-negative RA display significant risk allele frequency differences which are mainly confined to the HLA region. The data provide further support for distinct genetic aetiologies of RA subsets and emphasise the need to consider them separately in genetic as well as functional studies of this disease

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

Introduction: Liver enzymes are elevated in cardiometabolic diseases, particularly when there is non-alcoholic fatty liver disease. We therefore investigated if hypertension is associated with elevated levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase and γ-glutamyl transferase (GGT). Methods: We included 235 hypertensive and 708 normotensive subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 who had fewer than one alcoholic drink a week. In the follow-up study in 2005-2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension. Results: In CRISPS-2, plasma ALT (OR=1.31 per SD of log-transformed level, P=0.005) and GGT (OR=1.52 per SD of log-transformed level, P<0.001) were significantly associated with prevalent hypertension after adjusting for age, sex and body mass index (BMI). Among subjects not on anti-hypertensive medication, plasma ALP and GGT were significantly associated with both systolic blood pressure (beta=0.141, P<0.001 for ALP and beta=0.096, P=0.004 for GGT) and diastolic blood pressure (beta=0.131, P<0.001 for ALP and beta=0.102, P=0.004 for GGT). In forward stepwise logistic regression analysis of subjects normotensive at CRISPS-2, the highest tertile of plasma GGT level was an independent predictor of the development of hypertension in CRISPS-3 (OR=2.40, P=0.010), together with age, BMI, systolic blood pressure and plasma CRP at baseline, and change in BMI. The other liver enzymes were not significantly predictors of new-onset hypertension. Conclusions: Among the four liver enzymes, elevated GGT level is the strongest risk factor for hypertension in Hong Kong Chinese. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio

Role of genetic variants in gene encoding lipocalin-2 in the development of elevated blood pressure

Introduction: Lipocalin-2 is recently recognised as a biomarker of obesity and inflammation, which are both risk factors for hypertension. We therefore investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding lipocalin-2 (LCN2) with elevated blood pressure in Hong Kong Chinese. Methods: Five tagging SNPs were genotyped in 1936 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) with a median follow-up period of 6.4 years. Elevated blood pressure was defined as ≥130/85 mm Hg or taking anti-hypertensive medication. Results: There were only two haplotypes with frequency of >5%, namely AGATC (45.5%) and GGTCC (41.2%). Haplotype GGTCC was associated with elevated blood pressure at follow-up (OR=1.17 compared to haplotype AGATC, P=0.031 after adjusting for age and sex). Among 1381 subjects without elevated blood pressure at baseline, 321 subjects developed elevated blood pressure at follow-up. Haplotype GGTCC was associated with the development of elevated blood pressure at follow-up (OR=1.30 compared to haplotype AGATC, P=0.011 after adjusting for age, sex, systolic blood pressure, and follow-up duration; OR=1.44, P=0.0015 after further adjusting for other covariates). Among subjects not taking anti-hypertensive medication, carriers of the haplotype GGTCC had higher systolic blood pressure than non-carriers (119.7±16.4 mm Hg vs 117.9±17.3 mm Hg, P=0.043). Conclusion: Our findings suggest, for the first time, that genetic variants in LCN2 may affect blood pressure. Further studies on the role of lipocalin-2 in blood pressure regulation are warranted. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

Background: Plasma activities of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase, and γ-glutamyl transferase (GGT) are often increased in cardiometabolic diseases. We investigated if hypertension is associated with increased activities of these plasma markers. Methods: We included 235 hypertensive and 708 normotensive subjects (mean age 47.3 ± 9.6 and 58.0 ± 10.2. years respectively) from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 who had drank < 1/week. In the follow-up study in 2005-2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension. Results: Raised plasma ALT (OR = 1.22 per SD of log-transformed level, P=0.045) and GGT (OR = 1.38 per SD of log-transformed level, P=0.001) levels were associated with hypertension at baseline in CRISPS-2 after adjusting for covariates. Among subjects not on anti-hypertensive medications, plasma ALP, ALT and GGT were related to blood pressure (P< 0.01). In subjects normotensive at CRISPS-2, plasma GGT, but not ALP, ALT and AST, was an independent predictor of new-onset hypertension at CRISPS-3 (OR = 1.38 per SD of log-transformed level, P=0.020 and OR = 2.68 for 3rd tertile vs. 1st tertile, P=0.004) after adjusting for covariates. Conclusions: Among the 4 plasma markers, increased GGT activity is the strongest predictor for existing and new-onset hypertension in Hong Kong Chinese. © 2011 Elsevier B.V.postprin

Association of a genetic variant in adrenomedullin gene with its plasma level

published_or_final_versionThe 16th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 19, abstract no. 1

Association of a genetic polymorphism in the gene encoding fibrinogen beta chain with hypertension in Hong Kong Chinese

published_or_final_versionThe 15th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16, suppl. 1, p. 51, abstract no. 8

Mendelian randomisation analysis suggests that plasma interleukin-6 is raised in hypertension but does not cause its development

Introduction: Interleukin-6 (IL-6) plays a central role in inflammation and insulin resistance as well as atherogenesis. We investigated the associations of plasma IL-6 and its genetic variants with hypertension in both cross-sectional and prospective study designs. Methods: Plasma IL-6 was measured in 648 normotensive and 294 hypertensive subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 and three tagging SNPs in the IL-6 gene (IL6) were genotyped. Among subjects normotensive in CRISPS-2, 515 subjects were followed up in CRISPS-3 in 2005- 2008 and 100 of them had developed hypertension. Results: Plasma IL-6 correlated with systolic blood pressure (r=0.128, P<0.001), pulse pressure (r=0.144, P<0.001), and mean arterial pressure (r=0.086, P=0.008). Hypertensive subjects have significantly higher plasma IL-6 level after adjusting for age and sex (geometric mean [95% CI]=0.60 [0.54-0.65] vs 0.47 [0.44-0.50] pg/mL, P=0.021). In stepwise logistic regression, plasma IL-6 was associated with hypertension in women (P=0.004), but not in men. The SNP rs1800796 was associated with plasma IL-6 (beta= –0.098, P=0.002) in stepwise linear regression. However, this SNP was not associated with hypertension or blood pressure. Among subjects normotensive in CRISPS-2, plasma IL-6 was not associated with the development of hypertension in CRISPS-3. Conclusion: Elevated plasma IL-6 is associated with hypertension, especially in women. Plasma IL-6 is influenced by the SNP rs1800796. However, this SNP is not associated with hypertension, suggesting that hypertension is caused by other factors that elevate plasma IL-6. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio

Phenomenology of eta-gamma and eta'-gamma transition form factors at large momentum transfer

I discuss the progress in our theoretical understanding of the eta-gamma and eta'-gamma transition form factors, including the recent data from CLEO and L3 at large momentum transfer, Q^2. The experimental data above Q^2=1 GeV^2 can be well described by the hard scattering approach if the distribution amplitudes for eta and eta' mesons are taken close to the asymptotic one. Particular attention is paid to the interpretation of the data in terms of properly defined eta-eta' mixing parameters. I also comment on the use and misuse of interpolation formulas for P-gamma and P-gamma^* transition form factors.Comment: 6 pages + 4 figures (using espcrc2.sty, feynmp.sty); Talk presented at conference PHOTON'99, Freiburg, May 199