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  1. Mente A, O'Donnell MJ, Dagenais G, Wielgosz A, Lear SA, McQueen MJ, et al.
    J. Hypertens., 2014 May;32(5):1005-14; discussion 1015.
    PMID: 24569420 DOI: 10.1097/HJH.0000000000000122
    Although 24-h urinary measure to estimate sodium and potassium excretion is the gold standard, it is not practical for large studies. We compared estimates of 24-h sodium and potassium excretion from a single morning fasting urine (MFU) using three different formulae in healthy individuals.
  2. Lim WY, Kwek K, Chong YS, Lee YS, Yap F, Chan YH, et al.
    J. Hypertens., 2014 Apr;32(4):857-64.
    PMID: 24390251 DOI: 10.1097/HJH.0000000000000096
    OBJECTIVE: Greater maternal adiposity is a potentially modifiable risk factor for elevated blood pressure during pregnancy; however, the association has been little studied in Asian populations, and no study has evaluated potential differences in the adiposity-blood pressure relation between ethnic groups or interaction with gestational diabetes.

    METHODS: We performed a cross-sectional evaluation of a Singapore mother-offspring cohort comprising 799 pregnant Chinese, Malay and Indian women. Data on body weight, height, skinfold thickness and glycaemia (oral glucose tolerance test) were collected during the 2nd trimester; peripheral SBP and DBP were measured using an oscillometric device and central pressures by noninvasive radial applanation tonometry. The associations between adiposity measures BMI and sum of skinfold thickness and blood pressure outcomes were examined by linear regression with adjustment for potential confounders.

    RESULTS: Higher maternal BMI was associated with elevated peripheral and central pressures: the increases in pressure (mmHg) for each kg/m(2) increase in BMI were 1.19 (95% confidence interval, 1.03-1.36) for peripheral SBP, 0.76 (0.63-0.89) for peripheral DBP, 1.02 (0.87-1.17) for central systolic pressure and 0.26 (0.16-0.37) for central pulse pressure. The associations were generally stronger in Chinese women (P-interaction = 0.03 for central pulse pressure) and individuals with gestational diabetes (P-interaction = 0.03 for DBP and P-interaction = 0.046 for central systolic pressure). Similar patterns of results were found when using skinfold thickness as the measure of adiposity.

    CONCLUSION: Maternal adiposity is associated with higher peripheral and central blood pressures during pregnancy. Stronger associations in Chinese women and individuals with gestational diabetes warrant further investigation.
  3. Sng CC, Wong WL, Cheung CY, Lee J, Tai ES, Wong TY
    J. Hypertens., 2013 Oct;31(10):2036-42.
    PMID: 23787404 DOI: 10.1097/HJH.0b013e328362c201
    OBJECTIVE(S): To examine the effect of blood pressure (BP) on retinal vascular fractal dimension (Df), a measure of microvascular network complexity and density in a multiethnic cohort.
    METHODS: A population-based study of 3876 Chinese, Malay and Indian participants in Singapore. Retinal Df was measured using a computer-based program from digital retinal photographs. Associations between retinal Df and mean arterial BP (MABP) in the whole cohort and in each racial group were analysed using linear regression analysis. Logistic regression was used to examine the association between retinal Df and hypertension status.
    RESULTS: The mean retinal Df of the study population was 1.45 (standard deviation 0.03). After adjustment for age, sex, race, diabetes, BMI, cholesterol and creatinine levels, persons with smaller Df had higher MABP (mean difference MABP was 6.18 mmHg comparing lowest to highest Df quartiles, P<0.001). This was similar in Chinese, Malay and Indian persons [mean difference 6.40 (P<0.001), 4.72 (P=0.011) and 6.62 (P<0.001)mmHg, respectively]. Persons with smaller retinal Df were more likely to have uncontrolled treated or untreated hypertension [odds ratio 1.79 (P=0.003) and 2.60 (P=0.003), respectively, comparing lowest to highest Df quartiles] than those with no hypertension; this relationship was not seen comparing persons with controlled treated hypertension with no hypertension (odds ratio 1.01, P=0.972).
    CONCLUSION: Hypertension was associated with a sparser retinal vascular network, which was similar across different racial/ethnic groups and most apparent in those with uncontrolled or untreated hypertension. These data suggest that microvascular remodelling can be quantified by measuring retinal vasculature.
  4. Othman AS, Othman NI, Rosman A, Nudin SS, Rahman AR
    J. Hypertens., 2012 Aug;30(8):1552-5.
    PMID: 22635140 DOI: 10.1097/HJH.0b013e328355207b
    OBJECTIVES: In this cross-sectional study we compared the central aortic systolic pressure (CASP), peripheral brachial systolic pressure (PSP), peripheral brachial diastolic pressure (PDP) and augmentation index (AIx) between normotensive offspring of nonhypertensive parents (ONT) and normotensive offspring with at least one hypertensive parent (OHT).
    METHODOLOGY: A total of 100 healthy ONT (mean age 20.95 ± 2.06) and 100 healthy OHT (mean age 20.89 ± 2.12) individuals were recruited. Parental history of hypertension was determined by detailed history taking. CASP, PSP, PDP and AIx were measured using the BPro device. All blood pressure (BP) measurements were calibrated using oscillometric BP readings.
    RESULTS: The OHT group had higher PSP (117.57 ± 10.06 versus 114.52 ± 8.94, P < 0.05), PDP (72.39 ± 7.28 versus 70.39 ± 6.50, P < 0.05) and CASP (103.72 ± 8.95 versus 101.37 ± 7.74, P < 0.05) compared to the ONT group. There was no significant difference in AIx in the ONT group (57.97 ± 11.02 versus 58.08 ± 12.16, P = 0.95) in comparison to the OHT group. However, following adjustments for certain cardiovascular risk factors, only PSP (117.33 versus 114.76, P < 0.05) remained significantly higher in the OHT group compared to the ONT group. Analysis of adjusted data within sex showed that CASP was higher in the female OHT group compared to the female ONT group, whereas PDP were higher in the male OHT group compared to the male ONT group.
    CONCLUSION: Alterations in PSP, PDP and CASP are already present in early life in normotensive offspring of hypertensive parents, with possible differences in mechanism between different sexes.
    Study site: Clinical Research Laboratory in Cyberjaya University College of Medical Sciences, Selangor, Malaysia
  5. Cheung CY, Tay WT, Mitchell P, Wang JJ, Hsu W, Lee ML, et al.
    J. Hypertens., 2011 Jul;29(7):1380-91.
    PMID: 21558958 DOI: 10.1097/HJH.0b013e328347266c
    The present study examined the effects of blood pressure on a spectrum of quantitative and qualitative retinal microvascular signs.
  6. Strassheim V, Newton JL, Tan MP, Frith J
    J. Hypertens., 2016 Oct;34(10):1933-41.
    PMID: 27442791 DOI: 10.1097/HJH.0000000000001043
    OBJECTIVE: The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States.

    METHODS: MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis.

    RESULTS: Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)].

    CONCLUSION: Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension.

    REGISTRATION: PROSPERO ID CRD42015024612.

  7. Ching SM, Chia YC, Lim HM
    J. Hypertens., 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e56.
    PMID: 27753921
    Conference abstract:
    OBJECTIVE: This study aims to determine the relationship of long term visit to visit variability (VVV) of SBP and cardiovascular disease (CVD) in a primary care setting.
    DESIGN AND METHOD: This is a retrospective study of a cohort of 1416 patients over a period of 10 years (1998-2007). Demographic data, three monthly clinic BP readings and CVD events were captured from patient records. We derived the mean BP and VVV of SBPs for each subject and divided them into three groups defined as non hypertension, developed hypertension along the 10-year follow-up and persistent hypertension. We examined differences in cardiovascular events across these groups.
    RESULTS: Mean age of the participants at baseline was 56.5 ± 10.1 years, 34.6% were males. Table 1 describes mean SBP, BPV and CVD events of the study population.Those with both low mean SBP and low BPV have the lowest CVD events, conversely those with both high mean SBP and high BPV have highest CVD events. In those patients with the same mean SBP, whether high or low, those with higher BPV have more events than those with lower BPV. However patients with low mean SBP but high BPV have more CVD events compared with those patients with high mean SBP but low BPV (p = 0.04) suggesting BPV is more important than mean SBP in causing CVD events.We used ROC of VVV SBP to identify the cut off point of 12.9 mmHg as the indicator for increase in CVD events.
    CONCLUSIONS: In our study, we found that patients with hypertension have higher BPV than normotensive subjects. Furthermore those with higher BPV also had more CVD events. As such, we should prioritize lowering not only mean systolic BP but lowering BPV as well. Long term VVV SBP should be another target in the management of patients with hypertension.
  8. Lim HM, Chia YC, Ching SM
    J. Hypertens., 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e406.
    PMID: 27754262
    Conference abstract:
    We aim to examine the relationship between visit-to-visit systolic blood pressure variability (BPV) and decline in renal function in patients with hypertension and determine the level of systolic BPV that contribute to significant renal function decline.
  9. Zhou J, Lam B, Neogi S, Yeo G, Azizan E, Brown M
    J. Hypertens., 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e40.
    PMID: 27753883
    Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.
  10. Azizan E, Sukor N, Kamaruddin NA, Jamal AR, Ceral J, Solar M, et al.
    J. Hypertens., 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e550.
    PMID: 27754305
    Aldosterone-producing adenoma (APA) is a common curable cause of hypertension. Somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) have been found to cause the excess aldosterone production of two thirds of APAs [1-4]. KCNJ5 mutant APAs, the most common and largest, had explicit genotype-phenotype relationship - a low protein expression of KCNJ5 relative to their peritumoural zona glomerulosa (ZG) and a zona fasciculata-like composition [5-6]. Conversely for the other genes, controversy arises on whether they have the opposite cell phenotype [4,7-8]. This prospective study aim to to characterize the histopathological-specific mutation spectrum of APAs.
  11. Zhou J, Lam BY, Neogi SG, Yeo GS, Teo AE, Maniero C, et al.
    J. Hypertens., 2016 Sep;34 Suppl 2:e26.
    PMID: 27508643 DOI: 10.1097/01.hjh.0000491398.48468.bf
    Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). We recently performed a microarray assay using 21 pairs of zona glomerulosa (ZG) and zona fasciculata (ZF), and 14 paired APAs. This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.
  12. Lim HM, Chia YC, Ching SM
    J. Hypertens., 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e212-e213.
    PMID: 27754047 DOI: 10.1097/01.hjh.0000500462.09000.21
    Conference abstract:
    OBJECTIVE: To determine the minimum number and duration of blood pressure(BP) measurement needed to estimate long term visit-to-visit blood pressure variability (BPV) for predicting 10-year cardiovascular (CV) risk.
    DESIGN AND METHOD: This is a 10-year retrospective cohort study of 1403 patients from a primary care clinic. Three monthly BP readings per year were retrieved from 10 years of clinic visits. Standard deviation (SD) of systolic blood pressure (SBP) was used as a measure of BPV. SD was calculated for each cumulative year of readings. CV events defined as fatal and nonfatal coronary heart disease and fatal and nonfatal stroke. We used Pearson's correlation to examine the concordance between the SD of each additional year of follow-up and SD at the end of 10 years. Multiple logistic regression was used to estimate the CV risk and compare the odd ratio (OR) between 10-year SD and SD of each additional year of follow-up.
    RESULTS: Mean SD increased with more SBP measurements for each increasing year. Pearson's correlation increased with the years of SBP measurements indicating increasing concordance with 10-year SD when more years of SBP readings was included from the baseline. With 10-year SD, the OR for CV risk was associated with an increase in SD (OR 1.121, 95% CI 1.057-1.188, p 
  13. Chia YC
    J. Hypertens., 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e4-e5.
    PMID: 27753807
    Conference abstract:
    Hypertension is the leading cause of mortality worldwide. It is highly prevalent throughout the world. Even in regions liike South-East Asia (SEA) which has been perceived to be less prone to cardiovascular diseases, the prevalence of hypertension has been reported to be around 35% (1). Awareness and control of hypertension in SEA is also low, both being less than 50% each (2).Control of hypertension is an interplay between patients, doctors and system factors. One of the reasons for poor control of hypertension is resistant hypertension. Resistant hypertension is defined as blood presure that remains above goal despite being on three concurrent anti-hypertensive medications preferbaly one of which is a diuretic (3).True resistant hypertension should be differiented from secondary hypertension and pseudo-resistant hypertension. Resistant hypertension is almost always multi-factorial in aetiology. The exact prevalence of resistant hypertenion even in developed countries is not known It has been estimated that it is as high as 20-30% in clinical trial patients (4)Not many studies about resistant hypertension have been done in SEA but one done in an outpatient clinic in Thailand found it to be 7.82% Another study also done in a primary care clinc in Malaysia on 1217 patients with hypertension found the prevalence of resistant hypertension to be 8.8%. (6) Here it was found that the presence of chronic kidney disease was more likely to be associated with resistant hypertension (odds ratio [OR] 2.89, 95% confidence interval [CI] 1.56-5.35). Other factors like increasing age, female gender, presence of diabetes, obesity and left ventricular hypertrophyage which have been found to be predictors of resistant hypertension in other studies in the west were not seen in this study. There are various reasons for these findingsBut whatever the factors are that are associated with uncontrolled hypertension, the task is to sort out true resistant hypertension from pseudo-resistant hypertension and secondary casues of hypertension which may be treatable. A concerted effort is needed to reduce the BP in resistant hypertension. Failure to do so would mean a substantal increase in CV risk for the patient.
  14. Chia YC
    J. Hypertens., 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e16-e17.
    PMID: 27753834
    Conference abstract SY04-4: Many cardiovascular disease (CVD) risk prediction tools have been developed in an attempt to identify those at highest risk in order for them to benefit from interventional treatment. The first CVD risk tool that was developed was the coronary heart disease risk tool by the Framingham Heart Study in 1998 (1). However the Framingham Risk Score could overestimate (or underestimate) risk in populations other than the US population. Hence several other risk engines have also been developed, primarily for a better fit in the communities in which the tools are to be used (2, 3). Having said that the Framingham Heart Study risk tool has been validated in several populations (4, 5) and found to work reasonably well after some recalibration.Most risk prediction tools predict short term risk ie over a period of 10 years but since more recently risk tools now attempt to predict life-time risk or at least risk over the next 30 years. (6-8). The practical use of these risk prediction tools is that it is able to separate those at high risk (ie > 20% risk of a CVD event fatal or non-fatal event in the next 10 years) from those with the lowest risk (< 10% risk over 10 years). It then helps practitioners to triage them to either receive preventive therapy (high risk group) or none at all (low risk group) respectively. However in those with medium risk ie between 10-20%, the decision to offer treatment or not is less clear. In such a situation, other CVD risk factors for example family history of premature coronary heart disease, other biomarkers like elevated hs-CRP, presence of chronic kidney disease or albuminuria can be employed to further stratify risk.It is known that risk prediction tools are very much age dependent and in a younger individual with mildly raised CVD risk factors, his global CVD risk may be grossly under-estimated. Here additional CVD risk factors beyond those traditionally used in risk engines should be sought in order to recalibrate that individual's seemingly low risk and earlier intervention introduced if indeed he is of higher risk than what has been predicted by the conventional risk tools. Here too the use of life-time risk is probably of more importance than the traditional 10 year risk tool, again in order to identify those seemingly at "low" risk 10 year risk to receive treatment if the life-time risk is greater compared to an individual of the same age with optimal parameters. Furthermore while it is known that those with highest risk benefit the most from intervention, it is the population at large with the low or lower risk which contributes most to total CV morbidity and mortality in a country or community.Hence while short term risk prediction to identify those at highest risk is useful particularly in the presence of limited resources, attention should also be paid to those with short term low risk if the aim is to reduce CVD morbidity and mortality in any substantial way.
  15. Kulchaitanaroaj P, Brooks JM, Chaiyakunapruk N, Goedken AM, Chrischilles EA, Carter BL
    J. Hypertens., 2017 Jan;35(1):178-187.
    PMID: 27684354
    OBJECTIVE: To estimate long-term costs and outcomes attributable to a physician-pharmacist collaborative intervention compared with physician management alone for treating essential hypertension.

    METHODS: A Markov model cohort simulation with a 6-month cycle length to predict acute coronary syndrome, stroke, and heart failure throughout lifetime was performed. A cohort of 399 patients was obtained from two prospective, cluster randomized controlled clinical trials implementing physician-pharmacist collaborative interventions in community-based medical offices in the Midwest, USA. Framingham risk equations and other algorithms were used to predict the vascular diseases. SBP reduction due to the interventions deteriorated until 5 years. Direct medical costs using a payer perspective were adjusted to 2015 dollar value, and the main outcome was quality-adjusted life years (QALYs); both were discounted at 3%. The intervention costs were estimated from the trials, whereas the remaining parameters were from published studies. A series of sensitivity analyses including changing patient risks of vascular diseases, probabilistic sensitivity analysis, and a cost-effectiveness acceptability curve were performed.

    RESULTS: The lifetime incremental costs were $26 807.83 per QALY (QALYs gained = 0.14). The intervention provided the greatest benefit for the high-risk patients, moderate benefit for the trial patients, and the lowest benefit for the low-risk patients. If a payer is willing to pay $50 000 per QALY gained, in 48.6% of the time the intervention would be cost-effective.

    CONCLUSION: Team-based care such as a physician-pharmacist collaboration appears to be a cost-effective strategy for treating hypertension. The intervention is most cost-effective for high-risk patients.

  16. Chia YC, Ching SM, Lim HM
    J. Hypertens., 2017 05;35 Suppl 1:S50-S56.
    PMID: 28350621 DOI: 10.1097/HJH.0000000000001333
    OBJECTIVES: The current study aims to determine the relationship of long-term visit-to-visit variability of SBP to cardiovascular disease (CVD) in a multiethnic primary care setting.
    METHOD: This is a retrospective study of a cohort of 807 hypertensive patients over a period of 10 years. Three-monthly clinic blood pressure readings were used to derive blood pressure variability (BPV), and CVD events were captured from patient records.
    RESULTS: Mean age at baseline was 57.2 ± 9.8 years with 63.3% being women. The BPV and mean SBP over 10 years were 14.7 ± 3.5 and 142 ± 8 mmHg, respectively. Prevalence of cardiovascular event was 13%. In multivariate logistic regression analysis, BPV was the predictor of CVD events, whereas the mean SBP was not independently associated with cardiovascular events in this population. Those with lower SBP and lower BPV had fewer cardiovascular events than those with the same low mean SBP but higher BPV (10.5 versus 12.8%). Similarly those with higher mean SBP but lower BPV also had fewer cardiovascular events than those with the same high mean and higher BPV (11.6 versus 16.7%). Other variables like being men, diabetes and Indian compared with Chinese are more likely to be associated with cardiovascular events.
    CONCLUSION: BPV is associated with an increase in CVD events even in those who have achieved lower mean SBP. Thus, we should prioritize not only control of SBP levels but also BPV to reduce CVD events further.
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