Yoga's effect on inflammatory biomarkers and metabolic risk factors in a high risk population - a controlled trial in primary care.

BACKGROUND: Yoga can reduce blood pressure and has also been suggested to reduce inflammatory biomarkers and metabolic risk factors for cardiovascular diseases (CVDs). We aimed to assess the benefit of two yoga interventions on inflammatory biomarkers and metabolic risk factors in a high risk population in primary care. METHODS: Adult patients from a health care center in Sweden, with diagnosed hypertension, were invited to undergo a baseline check at the health care center. Baseline check included standardized blood pressure measurement, BMI and weight circumference measurements, blood sampling (hs-CRP, IL-6, FP-glucose, HbA1c, cholesterol, TG, LDL and HDL) and a questionnaire on self-rated quality of life (WHOQOL-BREF). There were three groups: 1) yoga class with yoga instructor; 2) yoga at home; and 3) a control group. In total, 83 patients were included and matched at the group level for systolic blood pressure. A majority of the patients (92 %) were on antihypertensive medication, which they were requested not to change during the study. After 12 weeks of intervention, the assessments were performed again. RESULTS: We recorded no evidence that yoga altered inflammatory biomarkers or metabolic risk factors in our study population. A total of 49 participants (59 %) met the criteria for metabolic syndrome. CONCLUSION: The yoga interventions performed in our study did not affect inflammatory biomarkers or metabolic risk factors associated with CVD in the study population of primary care patients with hypertension. Further randomized trials are needed to elucidate the effects of yoga on CVD risk factors in this particular group. TRAIL REGISTRATION: NCT01302535 , February 22, 2011.

Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study.

BACKGROUND: Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes. METHODS AND FINDINGS: We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006-2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31-1.95), heart failure (8.00, 2.64-24.2), peripheral vascular disease (1.92, 1.12-3.29), "other" CVD (1.26, 1.05-1.51), all CVD combined (1.35, 1.19-1.53), and all-cause mortality (1.93, 1.52-2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46-1.98), 4.40 (2.64-7.33), 2.46 (1.63-3.70), 1.40 (1.21-1.63), 1.64 (1.48-1.81), and 2.37 (1.87-3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22-2.26), atrioventricular and left bundle branch block (6.62, 1.86-23.56), and (peripheral) atherosclerosis (2.47, 1.18-5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16-2.35) and intracerebral haemorrhage (0.78, 0.20-2.97). CONCLUSIONS: These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.

Cardiovascular risk management in chronic kidney disease in general practice (the AusHEART study).

BACKGROUND: Chronic kidney disease (CKD) is common and increasing in prevalence. Adverse outcomes of CKD can be prevented through early detection and treatment. There is limited data on the awareness of CKD and the quality of care offered to patients with CKD in the primary care setting. The objectives of this study were to assess the prevalence, general practitioner (GP) awareness and extent of current evidence-practice gaps in the management of CKD in Australian primary care. METHODS: The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster stratified, cross-sectional survey among 322 GPs. Each GP was asked to provide data for 15-20 consecutive patients (age ≥ 55 years) who presented between April and June, 2008. The main outcome measures were CKD prevalence based on proteinuria and decreased estimated glomerular filtration rate. Evidence-practice gaps in management of patients with CKD were identified. RESULTS: Among a total of 4966 patients with kidney function test data, 1845 (37%) had abnormal kidney function. Of the 1312 patients with abnormal kidney function known to the GP at the time of visit, only 235 were correctly identified as having CKD. GPs under-estimated cardiovascular (CV) risks in patients with CKD when compared with the prevailing guidelines at the time of survey and the recent national guidelines, particularly in later stages of CKD. Among CKD patients not prescribed blood pressure-lowering agents or lipid-lowering agents, treatment was indicated as per relevant guidelines in 51 and 46%, respectively. For CKD patients who were already prescribed blood pressure-lowering and lipid-lowering agents, 61 and 50%, respectively, did not meet the treatment targets recommended by the relevant guidelines. CONCLUSIONS: CKD is common, significantly under-recognized and under-treated in primary care. Effort to increase awareness and provide opportunities for improved screening and assessment should improve the management and outcome of these patients at high risk of CV disease.

How fair is Medicare? The income-related distribution of Medicare benefits with special focus on chronic care items.

OBJECTIVE: To use patient-level data, clinical information and linked Medicare records to assess the distribution of benefits (rebates) across income groups, including benefits relating to chronic conditions such as the Chronic Disease Dental Scheme (CDDS). DESIGN, SETTING AND PARTICIPANTS: Nationally representative, cluster-stratified survey (the Australian Hypertension and Absolute Risk Study) involving 322 general practitioners who each collected clinical data on 15-20 patients aged≥55,2012s who presented between 1 April 2008 and 30 June 2008 and who consented to have their information linked with Medicare administrative records over 12 months. MAIN OUTCOME MEASURES: Distribution of total out-of-hospital Medicare expenditure quantified using concentration indices and determinants of use calculated by odds ratios. RESULTS: There were 2862 patients in the study. After controlling for need, the concentration index for overall funding was slightly progressive (pro-poor) at -0.008 (95% CI, -0.009 to -0.008). Medicare expenditure on chronic care-related services consistently contributed to progressivity of the overall scheme, particularly services under the CDDS with a need-adjusted concentration index of -0.205 (95% CI, -0.208 to -0.201). Uptake of chronic care items varied by locality and comorbid conditions (there was greater uptake by patients with one or more comorbid conditions). CONCLUSIONS: Chronic care items, particularly dental items, have primarily been used by individuals from lower income households. Uptake of chronic care items contributes to the overall progressivity of Medicare.

Perindopril-based blood pressure-lowering therapy reduces amino-terminal-pro-B-type natriuretic peptide in individuals with cerebrovascular disease.

OBJECTIVE: The plasma amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) level predicted congestive heart failure, myocardial infarction, and ischaemic stroke in participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of the effects of blood pressure lowering on cardiovascular events among individuals with cerebrovascular disease. Active treatment comprised a flexible regimen based on perindopril, with the addition of indapamide at the discretion of treating physicians. Active treatment reduced cardiovascular events, and we therefore investigated whether active treatment modified NT-proBNP and other cardiovascular risk factors. METHODS: We measured NT-proBNP and other cardiovascular risk factors at randomization and after 13 months of therapy in a subset of 357 PROGRESS participants. RESULTS: Baseline systolic and pulse pressures were higher in individuals with elevated baseline NT-proBNP levels. In comparison with placebo, active treatment reduced the blood pressure and NT-proBNP levels, and increased renin levels. Reduction of NT-proBNP levels by active treatment was most evident in individuals with baseline NT-proBNP levels in the highest quarter (> 26 pmol/l), with a median reduction of 16 pmol/l (interquartile range 0-51 pmol/l, P = 0.004), corresponding to a median decrease of 39% (interquartile range 0-69%). Active treatment reduced blood pressure similarly for individuals in each of the four quarters of baseline NT-proBNP. Active therapy had no effect on plasma lipid, C-reactive protein, homocysteine, or soluble vascular cell adhesion molecule 1 levels. CONCLUSION: We conclude that plasma NT-proBNP level, in addition to predicting cardiovascular risk, may provide a measure of risk reduction by blood pressure-lowering therapy.

Prediction of myocardial infarction by N-terminal-pro-B-type natriuretic peptide, C-reactive protein, and renin in subjects with cerebrovascular disease.

BACKGROUND: B-type natriuretic peptide (BNP), C-reactive protein (CRP), and renin are elevated in persons at risk for cardiovascular disease. However, data that directly compare these markers in the prediction of myocardial infarction (MI) are limited. METHODS AND RESULTS: N-terminal-proBNP (NT-proBNP), CRP, and renin were measured in baseline blood samples from a nested case-control study of the 6105 participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack. Each of 206 subjects who experienced MI, either fatal or nonfatal, during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. Most MI cases (67%) occurred in subjects without a history of coronary heart disease. NT-proBNP, CRP, and renin each predicted MI; the odds ratio for subjects in the highest compared with the lowest quarter was 2.2 (95% CI, 1.3 to 3.6) for NT-proBNP, 2.2 (95% CI, 1.3 to 3.6) for CRP, and 1.7 (95% CI, 1.1 to 2.8) for renin. NT-proBNP and renin, but not CRP, remained predictors of MI after adjustment for all other predictors, including LDL and HDL cholesterol levels. Individuals with both NT-proBNP and renin in their highest quarters had 4.5 times the risk of MI compared with subjects with both biological markers in their lowest quarters. CONCLUSIONS: NT-proBNP and renin, but not CRP, are independent predictors of MI risk after stroke or transient ischemic attack, providing information additional to that provided by classic risk factors, and may enable more effective targeting of MI prevention strategies.

Soluble vascular cell adhesion molecule 1 and N-terminal pro-B-type natriuretic peptide in predicting ischemic stroke in patients with cerebrovascular disease.

BACKGROUND: Patients with stroke or transient ischemic attack are at high risk of another stroke, and there is need for improved strategies to predict recurrent stroke. OBJECTIVE: To assess the prognostic value of levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size in patients with previous stroke or transient ischemic attack. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study of participants of the Perindopril Protection Against Recurrent Stroke Study was performed. The Perindopril Protection Against Recurrent Stroke Study was a placebo-controlled trial of a perindopril erbumine-based, blood pressure-lowering regimen that reduced ischemic stroke risk by 24% among individuals with previous stroke or transient ischemic attack. Each of 252 patients who experienced ischemic stroke during a mean follow-up of 3.9 years was matched to 1 to 3 control patients. Matching variables were age, sex, treatment allocated, region, and most recent qualifying event at randomization. MAIN OUTCOME MEASURES: Risk of ischemic stroke predicted by baseline levels of sVCAM-1, NT-proBNP, C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size. RESULTS: Levels of sVCAM-1 and NT-proBNP predicted recurrent ischemic stroke. The odds ratio for patients in the highest, as compared with the lowest, quarter was 2.24 (95% confidence interval, 1.35-3.73) for sVCAM-1 level and 1.62 (95% confidence interval, 0.98-2.69) for NT-proBNP level, after adjustment for matching and other risk factors. Patients in the highest quarters for both sVCAM-1 and NT-proBNP levels had 3.6 times the risk of recurrent ischemic stroke compared with patients in the lowest quarters for both biologic markers. Level of sVCAM-1 was similarly predictive of ischemic stroke in patients allocated to placebo and perindopril-based therapy. Baseline plasma levels of C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size did not predict recurrent ischemic stroke risk. CONCLUSION: Measurement of sVCAM-1 and NT-proBNP levels provides prognostic information for recurrent ischemic stroke beyond traditional risk factors.

The effects of reduced copayments on discontinuation and adherence failure to statin medication in Australia.

This paper assesses whether the concession card, which offers discounted out-of-pocket costs for prescription medicines in Australia, affects discontinuation and adherence to statin therapy. The analysis uses data from the Australian Hypertension and Absolute Risk Study (AusHEART), which involves patients aged 55 years and over who visited a GP between April and June 2008. Socioeconomic and clinical information was collected and linked to administrative data on pharmaceutical use. Patients without a concession card were 63% more likely (hazard ratio (HR) 95% confidence interval (CI): 1.14-2.33) to discontinue and 60% (odds ratio (OR) CI: 1.04-2.44) more likely to fail to adhere to therapy compared to concessional patients. Smokers were 2.12 (HR CI: 1.39-3.22) times more likely to discontinue use and 2.23 (OR CI: 1.35-3.71) times more likely to fail to adhere compared to non-smokers. Patients who had recently initiated statin medication were also 2.28 (HR CI: 1.22-4.28) times more likely to discontinue use. In conclusion, higher copayments act as a disincentive for persistent and adherent use of statin medication.

Cardiovascular risk perception and evidence--practice gaps in Australian general practice (the AusHEART study).

OBJECTIVE: To examine the perception and management of cardiovascular disease (CVD) risk in Australian primary care. DESIGN, SETTING AND PARTICIPANTS: The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster-stratified, cross-sectional survey of 322 general practitioners. Each GP was asked to collect data on CVD risk factors and their management in 15-20 consecutive patients aged >or= 55 years who presented between April and June 2008, and to estimate each patient's absolute risk of a cardiovascular event in the next 5 years. MAIN OUTCOME MEASURES: Estimated 5-year risk of a cardiovascular event, proportion of patients receiving appropriate treatment. RESULTS: Among 5293 patients, 29% (1548) had established CVD. A further 22% (1145), when categorised according to the 2009 National Vascular Disease Prevention Alliance guideline, to 42% (2211), when categorised according to National Heart Foundation (NHF) 2004 guideline, had a high (>or= 15%) 5-year risk of a cardiovascular event. Of the 1548 patients with established CVD, 50% were prescribed a combination of a blood pressure (BP)-lowering medication, a statin and an antiplatelet agent, and 9% were prescribed a BP-lowering medication and a statin but not an antiplatelet agent. Among high-risk patients without established CVD, categorised using NHF 2004 adjustments, 34% were prescribed a combination of a BP-lowering medication and a statin. GPs estimated 60% of patients with established CVD as having a risk of less than 15%. The GPs' estimates of risk among patients without established CVD agreed with the centrally calculated estimate (according to the NHF 2004 guideline) in 48% of instances (Kappa = 0.21). CONCLUSIONS: These data confirm substantial undertreatment of patients who are at high risk of a cardiovascular event. We recommend that GPs assess absolute risk for older patients and ensure that high-risk patients receive evidence-based pharmacotherapy.

Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Low-density lipoprotein particles and risk of intracerebral haemorrhage in subjects with cerebrovascular disease.

BACKGROUND: Only limited data are available for risk factors for intracerebral haemorrhage (ICH) in subjects with established cerebrovascular disease. DESIGN: We performed a nested case-control study of participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). This was a randomized, placebo-controlled trial that established the beneficial effects of blood pressure lowering in 6105 patients with cerebrovascular disease. METHODS: Each of 41 subjects who experienced ICH during a mean follow-up of 3.9 years was matched to 1-3 control subjects. Lipoprotein particles and other plasma markers were measured in baseline blood samples from PROGRESS participants. RESULTS: In comparison with control subjects, ICH cases had increased mean low-density lipoprotein (LDL) diameter (P=0.04) and increased large LDL particle concentration (P=0.03). The odds ratio (adjusted for regression dilution bias) for ICH risk with 10 mmHg increase in systolic blood pressure (SBP) was 1.45 (95% confidence interval: 1.01-2.09, P=0.05), with a 1 nm increase in mean LDL diameter it was 2.15 (95% confidence interval: 0.97-4.77, P=0.06), and with 100 nmol/l increase in large LDL particle concentration it was 1.18 (95% confidence interval: 0.98-1.43, P=0.08). Plasma levels of C-reactive protein (CRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), homocysteine, amino-terminal-pro-B-type natriuretic peptide (NT-proBNP), and renin were not associated with ICH risk. CONCLUSION: SBP predicted ICH risk in subjects with cerebrovascular disease, whereas CRP, sVCAM-1, homocysteine, NT-proBNP, and renin did not predict ICH risk. The trends for prediction of ICH risk by mean LDL particle diameter and large LDL particle concentration are hypothesis generating and require confirmation in larger studies.

Prediction of heart failure by amino terminal-pro-B-type natriuretic peptide and C-reactive protein in subjects with cerebrovascular disease.

B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor-based therapy.

Lowering blood pressure in 2003.

The foundation of treatment for patients with hypertension is ongoing use of lifestyle measures such as physical exercise, weight reduction, and salt restriction. There should be emphasis on reduction of total cardiovascular risk, including smoking cessation and achievement of goal blood pressures. There are now five classes of first-line blood-pressure-lowering drugs - diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium antagonists. In most patients, the choice of drug will be guided by the clinical situation in the individual patient, including the presence of target organ damage, diabetes, established vascular or kidney disease, or other comorbidities. In the absence of such clinical indications, start drug therapy with a low-dose diuretic. Combination therapy will be needed in around two-thirds of patients, and a diuretic will normally form one element of most combinations, with the second or third drug coming from among the remaining four. Consider the use of fixed-dose combinations to improve adherence to therapy. Use long-acting, once-daily preparations.

Reductions in the risks of recurrent stroke in patients with and without diabetes: the PROGRESS Trial.

BACKGROUND: Analyses of the risks of stroke were conducted for subjects with and without diabetes, participating in a randomized, double-blind, placebo-controlled trial of a perindopril-based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack (TIA), followed for a median of 3.9 years. FINDINGS: Seven hundred and sixty-one patients had diabetes at baseline. Diabetes increased the risk of recurrent stroke by 35% (95% CI 10-65%) principally through an effect on ischaemic stroke (1.53, 95% CI 1.23-1.90). Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes. The proportional risk reductions achieved for stroke in patients with diabetes, 38% (95% CI 8-58%), and patients without diabetes, 28% (95% CI 16-39%), were not significantly different (p homogeneity = 0.5). The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 (95% CI 9-111) patients treated for 5 years. CONCLUSIONS: Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease. Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes.