[show abstract][hide abstract] ABSTRACT: We determined clinical predictors of the rate of rise (RoR) in blood pressure in the morning as well as a novel measure of the power of the BP surge (BPpower) derived from ambulatory blood pressure recordings.
BPpower and RoR were calculated from 409 ambulatory blood pressure (ABP) recordings from subjects attending a cardiovascular risk clinic. Anthropometric data, blood biochemistry, and history were recorded. The 409 subjects were 20-82 years old (average 57, SD = 13), 46% male, 9% with hypertension but not on medication and 34% on antihypertensive medication.
Average RoR was 11.1 mmHg/hour (SD = 8) and BPpower was 273 mmHg2/hour (SD = 235). Only cholesterol, low density lipoprotein and body mass index (BMI) were associated with higher BPpower and RoR (P<0.05) from 25 variables assessed. BPpower was lower in those taking beta-blockers or diuretics. Multivariate analysis identified that only BMI was associated with RoR (4.2% increase/unit BMI, P = 0.020) while cholesterol was the only remaining associated variable with BPpower (17.5% increase/mmol/L cholesterol, P = 0.047). A follow up of 213 subjects with repeated ABP after an average 1.8 years identified that baseline cholesterol was the only predictor for an increasing RoR and BPpower (P<0.05). 37 patients who commenced statin subsequently had lower BPpower whereas 90 age and weight matched controls had similar BPpower on follow-up.
Cholesterol is an independent predictor of a greater and more rapid rise in morning BP as well as of further increases over several years. Reduction of cholesterol with statin therapy is very effective in reducing the morning blood pressure surge.
PLoS ONE 01/2014; 9(3):e93186. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIM: A number of studies have examined if WCHT is associated with increased cardiovascular risk but with definitions of WCHT that were not sufficiently robust, and results have been inconsistent. This review aims to standardise the evidence by only including studies which used a definition of WCHT consistent with international guidelines. METHOD: Published studies were reviewed for data on vascular dysfunction, target organ damage, risk of future sustained hypertension and cardiovascular events. FINDINGS: WCHT has a population prevalence of approximately 15% and is associated with non-smoking and slightly elevated clinic blood pressure. Compared to normotensives, subjects with WCHT are at increased cardiovascular risk due to a higher prevalence of glucose dysregulation, increased left ventricular mass index and increased risk of future diabetes and hypertension. CONCLUSION: Management of a subject with WCHT should focus on cardiovascular risk factors, particularly glucose intolerance, not blood pressure alone. This article is protected by copyright. All rights reserved.
Clinical and Experimental Pharmacology and Physiology 05/2013; · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: A morning blood pressure surge (MBPS) may be either a mechanism for, or a marker of, increased cardiovascular events. This study has examined factors which may influence the morning surge: age, gender, metabolic factors, sympathetic function, blood pressure and arterial stiffness. Four measures of the MBPS were examined-sleep-trough surge, pre-awake surge, rate of blood pressure rise and a Power function. Subjects underwent ambulatory blood pressure monitoring, glucose tolerance test, central pulse wave velocity, sympathetic autonomic function tests (mental stress and sustained handgrip). MBPS was associated with age, hypertension, blood pressure variability and serum lipids. After adjustment for age and waist circumference, all four measures of MBPS remained positively associated with low-density lipoprotein (LDL) cholesterol. The novel finding of a significant relationship between measures of MBPS and LDL-cholesterol is an intriguing link between two major cardiovascular risk factors.Journal of Human Hypertension advance online publication, 22 November 2012; doi:10.1038/jhh.2012.44.
Journal of human hypertension 11/2012; · 2.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although most national guidelines for the diagnosis and management of hypertension emphasize that the initiation and modification of blood pressure (BP)-lowering treatment should be related to absolute cardiovascular disease (CVD) risk, there is only limited information on how to incorporate ambulatory BP (ABP) monitoring into this framework. The objective of this initiative is to provide ABP equivalents for BP cut-points for treatment initiation and targets to be included into guidelines.
A critical analysis of the best available evidence from clinical trials and observational studies was undertaken to develop a new consensus statement for ABP monitoring.
ABP monitoring has an important place in defining abnormal patterns of BP, particularly white-coat hypertension (including in pregnancy), episodic hypertension, masked hypertension, labile BP and nocturnal or morning hypertension. This consensus statement provides a framework for appropriate inclusion of ABP equivalents for low, moderate and high CVD risk patients. The wider use of ABP monitoring, although justified, is limited by its availability and cost due to the lack of medical subsidy in Australia. However, cost-benefit analysis does suggest a cost-saving in reduced numbers of inappropriate antihypertensive treatments.
Although clinic measurement of BP will continue to be useful for screening and management of suspected and true hypertension, ABP monitoring provides considerable added value toward accurate diagnosis and the provision of optimal care in uncomplicated hypertension, as well as for patients with moderate or severe CVD risk.
Journal of hypertension 12/2011; 30(2):253-66. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Isolated clinic hypertension (ICHT) may be an indicator of both future hypertension and diabetes. This study examines the 2-h plasma glucose level post load (2hPG), and measures of arterial stiffness, autonomic function and circulating biomarkers in ICHT, normotension and hypertension.
Participants aged 39-75 years, who were untreated for hypertension, nonsmokers and not known diabetic (n=105) were categorized as normotension, ICHT and hypertension, based on clinic and mean daytime ambulatory blood pressures. Participants had measurements of autonomic function, aorto-femoral pulse wave velocity (PWVc), as well as blood sampling for lipids and potential circulating biomarkers [high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), asymmetric dimethylarginine (ADMA), and von Willebrand factor (vWF)], followed by a glucose tolerance test.
A total of 8.3% normotension, 37.9% ICHT and 15% hypertension patients had impaired glucose tolerance. Mean 2hPG adjusted for age and waist circumference was 5.7 mmol/l [interquartile range (IQR) 5.2-6.4] for normotension, 7.4 mmol/l (IQR 6.5-8.3) for ICHT (P=0.002 vs. normotension) and 6.2 mmol/l (IQR 5.6-6.9) for hypertension group. Other measures of insulin resistance were similar in the three groups. Mental stress testing induced a greater blood pressure response in the ICHT group (P=0.01 vs. normotension); other autonomic function measures were similar in the three groups. Mean PWVc, adjusted for age and blood pressure, was similar in ICHT and normotension but increased in the hypertension group. Circulating biomarker levels were not different in the three groups.
Assessment of total cardiovascular risk in patients with ICHT should include measurement of postprandial glucose.
Journal of hypertension 12/2010; 29(4):749-57. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: End-stage kidney disease registry data have reported increased mortality in patients with diabetes as compared with those without. Here we examine whether diabetes is independently associated with an increased risk of major cardiovascular events and death in patients with advanced chronic kidney disease (CKD).
Data from 315 participants with CKD in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) were assessed. Primary end-points were fatal or non-fatal cardiovascular events, including myocardial infarction, stroke, unstable angina, coronary revascularisation and peripheral vascular events assessed both jointly and separately using Cox-proportional hazard models.
Twenty-three per cent reported diabetes. Median follow up was 3.6 years. In those with diabetes, an increased risk for major cardiovascular events was observed, crude hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.11-3.90). After adjustment for age, gender, smoking, systolic blood pressure, body mass index, past ischaemic heart disease and use of preventive therapies, diabetes was associated with an HR of 1.83 (1.28-2.61) for major cardiovascular events. The risk for peripheral vascular events was also increased, adjusted HR 6.31 (2.61-15.25). For all-cause death, major coronary and stroke events, the risk in those with diabetes was not significantly increased (all-cause death, adjusted HR 1.31 (95% CI 0.80-2.14); major coronary events, adjusted HR 1.26 (95% CI 0.64-2.49); and major stroke events, adjusted HR 1.28 (95% CI 0.55-2.99)).
Diabetes significantly increases the risk of major cardiovascular events, especially peripheral vascular events in patients with advanced CKD. Trials of multifactorial management of cardiovascular risk factors are required to determine if outcomes for this population may be improved.
Internal Medicine Journal 03/2010; 41(12):825-32. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Twenty-four hour ambulatory blood pressure thresholds have been defined for the diagnosis of mild hypertension but not for its treatment or for other blood pressure thresholds used in the diagnosis of moderate to severe hypertension. We aimed to derive age and sex related ambulatory blood pressure equivalents to clinic blood pressure thresholds for diagnosis and treatment of hypertension.
We collated 24 hour ambulatory blood pressure data, recorded with validated devices, from 11 centres across six Australian states (n=8575). We used least product regression to assess the relation between these measurements and clinic blood pressure measured by trained staff and in a smaller cohort by doctors (n=1693).
Mean age of participants was 56 years (SD 15) with mean body mass index 28.9 (5.5) and mean clinic systolic/diastolic blood pressure 142/82 mm Hg (19/12); 4626 (54%) were women. Average clinic measurements by trained staff were 6/3 mm Hg higher than daytime ambulatory blood pressure and 10/5 mm Hg higher than 24 hour blood pressure, but 9/7 mm Hg lower than clinic values measured by doctors. Daytime ambulatory equivalents derived from trained staff clinic measurements were 4/3 mm Hg less than the 140/90 mm Hg clinic threshold (lower limit of grade 1 hypertension), 2/2 mm Hg less than the 130/80 mm Hg threshold (target upper limit for patients with associated conditions), and 1/1 mm Hg less than the 125/75 mm Hg threshold. Equivalents were 1/2 mm Hg lower for women and 3/1 mm Hg lower in older people compared with the combined group.
Our study provides daytime ambulatory blood pressure thresholds that are slightly lower than equivalent clinic values. Clinic blood pressure measurements taken by doctors were considerably higher than those taken by trained staff and therefore gave inappropriate estimates of ambulatory thresholds. These results provide a framework for the diagnosis and management of hypertension using ambulatory blood pressure values.
[show abstract][hide abstract] ABSTRACT: Background: Twenty-four hour ambulatory blood pressure (ABP) thresholds exist for the diagnosis of mild hypertension but not for other blood pressure (BP) thresholds used either in the diagnosis of moderate-severe hypertension or its treatment. We aimed to derive age and sex differentiated ABP equivalents for both hypertension diagnosis and treatment thresholds.
Methods: Twenty-four ABP data recorded with validated devices were collated from 11 centres across six Australian States (n=8,575) and related to clinic systolic BP (SBP) and diastolic BP (DBP) measured by health professional staff or by physician using least product regression.
Results: Subjects were 56 years old (54% female), with body mass index 28.9 kg/m2 and clinic SBP/DBP of 142/82 mmHg. Average clinic measures were 6/3 mmHg higher than daytime ABP and 10/5 mmHg higher than 24 hour ABP. Staff-measured clinic BP was 9/7 mmHg lower than physician-measured BP. Daytime ABP equivalents were 4/3 mmHg lower at the 140/90 mmHg threshold (lower limit of grade 1 hypertension), 2/2 mmHg lower at 130/80 mmHg (upper limit with associated conditions), and 1/1 mmHg lower at 125/75 mmHg. Equivalents were 3/2 mmHg lower for females and 2-4 mmHg lower in older subjects.
Conclusions: Our study provides daytime ABP thresholds for target clinic BP which are slightly below clinic values when the latter are measured by professional staff. Physician measurements of clinic BP were considerably higher, which inappropriately modified estimates of ABP treatment thresholds. These results provide a framework for the diagnosis and management of hypertension using ABP.
[show abstract][hide abstract] ABSTRACT: To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD).
Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye.
160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46).
The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.
[show abstract][hide abstract] ABSTRACT: To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome.
Randomized controlled trial.
Controlled clinical study.
Overweight age- and body mass index-matched women with polycystic ovary syndrome.
Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 microg ethinyl E(2)-2 mg cytoproterone acetate, n = 30).
Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism.
The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL).
In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear.
Fertility and sterility 12/2008; 93(1):184-91. · 3.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the feasibility, reliability and acceptability of the mini clinical evaluation exercise (mini-CEX) for performance assessment among international medical graduates (IMGs).
Observational study of 209 patient encounters involving 28 IMGs and 35 examiners at three metropolitan teaching hospitals in New South Wales, Victoria and Queensland, September-December 2006.
The reliability of the mini-CEX was estimated using generalisability (G) analysis, and its acceptability was evaluated by a written survey of the examiners and IMGs.
The G coefficient for eight encounters was 0.88, suggesting that the reliability of the mini-CEX was 0.90 for 10 encounters. Almost half of the IMGs (7/16) and most examiners (14/18) were satisfied with the mini-CEX as a learning tool. Most of the IMGs and examiners enjoyed the immediate feedback, which is a strong component of the tool.
The mini-CEX is a reliable tool for performance assessment of IMGs, and is acceptable to and well received by both learners and supervisors.
The Medical journal of Australia 09/2008; 189(3):159-61. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: 1. This review examines the current evidence for altered mechanical and circulating biomarkers in isolated clinic hypertension and their potential significance. 2. Arterial stiffness, as assessed by central pulse wave velocity, is influenced by multiple cardiovascular risk factors; however, an independent association with isolated clinic hypertension (ICHT) has not been convincingly shown in four small studies. 3. Endothelial dysfunction, as assessed by brachial artery flow-mediated vasodilation, circulating levels of endothelial markers (e.g. nitrite/nitrate, von Willebrand factor, endothelin-1) and/or circulating levels of inhibitors of vascular nitric oxide (plasma asymmetric dimethylarginine, homocysteine), has been shown to be present in established hypertension and to a variable and inconsistent extent in subjects with ICHT. 4. Evidence of increased oxidative stress in ICHT versus normotensive subjects was found in two of three studies. 5. Circulating inflammatory markers C-reactive protein and plasminogen activator inhibitor-1 were significantly increased in two of three and two of two studies, respectively, in ICHT compared with normotensive subjects. 6. Urinary albumin excretion is a marker of both arterial and renal disease. The consensus from seven studies in patients with ICHT is that albuminuria is not an independent marker for ICHT. 7. Studies to date assessing biomarkers in ICHT have been small and cross-sectional. Larger, long-term longitudinal studies of arterial functional and circulating biomarkers are required to assess the potential vascular impact of ICHT.
Clinical and Experimental Pharmacology and Physiology 05/2008; 35(4):402-8. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The contribution of obesity to the occurrence of cardiovascular events may not be wholly related to its influence on traditional risk factors. Coagulation and fibrinolysis may also influence cardiovascular risk, but the relationship of adiposity with these processes is unclear. The aim of the present study was to investigate the relationships of BMI (body mass index), waist circumference, hip circumference and WHR (waist-to-hip ratio) with VIIc (factor VII activity), plasma markers of thrombin generation [F1+2 (prothrombin fragment 1+2)], fibrin formation [SF (soluble fibrin)] and fibrin turnover (D-dimer), and PAI-1 (plasminogen activator inhibitor-1; a marker of fibrinolytic inhibitory capacity). The study cohort was 80 healthy postmenopausal women who were not diabetic, current smokers or taking hormone therapy and who had a fasting sample of blood collected. VIIc, F1+2, SF and PAI-1 were all positively correlated with BMI, waist circumference and WHR, whereas D-dimer was positively correlated with waist circumference and WHR, but not BMI. WHR was the strongest correlate of all the markers except for PAI-1, which was most closely related to BMI. Hip circumference became a negative correlate of F1+2 and D-dimer after adjusting for waist circumference. The relationships of WHR with F1+2 and SF, but not with VIIc and D-dimer, were independent of traditional risk factors. The positive association between waist circumference and markers of thrombin generation, fibrin production and fibrin turnover suggests that abdominal adiposity may contribute to atherothrombosis by activating intravascular coagulation. In contrast, a larger hip circumference appears to have a protective affect against coagulation activation.
[show abstract][hide abstract] ABSTRACT: Indices of arterial structure and stiffness are proposed as surrogate markers of cardiovascular disease in patients with chronic kidney disease (CKD), but no study examined multiple markers in the same population.
Prospective observational study.
315 subjects with stages 4 to 5 CKD, aged 24 to 79 years (mean age, 56.6 +/- 13.6 [SD] years), enrolled in the Atherosclerosis and Folic Acid Supplementation Trial.
Carotid arterial intima-medial thickness (IMT; n = 315) and indices of arterial stiffness (n = 207), including aortofemoral pulse wave velocity (PWV[a-f]), systemic arterial compliance (SAC), and carotid-derived augmentation index.
The primary outcome was a composite of all fatal and nonfatal cardiovascular events.
During follow-up (median, 3.6 years), 95 cardiovascular events occurred. On Cox proportional-hazard modeling, mean maximum IMT, PWV(a-f), and SAC were predictive of the composite clinical end point of all cardiovascular events, but carotid-derived augmentation index was not (hazard ratio [HR] for every 0.01-mm increase in IMT, 1.09; P = 0.001; 95% confidence interval [CI], 1.03 to 1.14; HR for every 1-m/s increase in PWV(a-f), 1.18; P < 0.001; 95% CI, 1.12 to 1.25; HR for every 0.01-U/mm Hg decrease in SAC, 0.98; P = 0.01; 95% CI, 0.97 to 0.99). After adjustment for age, sex, blood pressure, diabetes, past cardiovascular disease, cholesterol level, and smoking, PWV(a-f) remained a significant independent predictor of cardiovascular events (adjusted HR, 1.12; P = 0.001; 95% CI, 1.05 to 1.20), but IMT and SAC did not.
Study power to analyze differences between predialysis and dialysis stages of CKD.
PWV(a-f) is the only arterial index independently associated with cardiovascular outcome in patients with CKD.
American Journal of Kidney Diseases 11/2007; 50(4):622-30. · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Confederation of Postgraduate Medical Education Councils launched the Australian Curriculum Framework for Junior Doctors in October 2006. The curriculum framework: balances the major areas of clinical management, communication and professionalism, and highlights the importance of an integrated approach to prevocational learning and teaching; supports practice-based, opportunistic and continuous learning, and specifies performance and supervision requirements for junior doctors; and has been published in both Internet and printable versions, to make the document accessible and easily usable by junior doctors and supervisors. The implementation of the curriculum framework will be overseen by a steering group that includes representatives from key stakeholder groups, including junior doctors and medical students.
The Medical journal of Australia 05/2007; 186(7 Suppl):S14-9. · 2.85 Impact Factor