Participants' views of ultra-low dose combination therapy for high blood pressure: a mixed-methods study from the QUARTET trial.

Single-pill combination therapy containing four quarter-dose medications for high blood pressure improves BP control compared to monotherapy, however patient-reported acceptance of the quadpill as a treatment strategy remains undescribed. We collected within-trial feedback and interviewed participants from the quadruple ultra-low-dose treatment for hypertension (QUARTET) trial to characterise patient attitudes to this intervention. All trial participants were asked about ease and preference for the quadpill and provided an opportunity to give further comments on the trial at 12 weeks (trial primary endpoint) and 52 weeks extended follow-up. Separately, we used purposive and quota sampling for the semi-structured telephone interviews, with the resultant verbatim transcripts analysed using an inductive thematic analysis approach. Themes were re-evaluated after each successive interview, and at suspected data saturation, an additional interview conducted for confirmation. At 12 weeks follow-up, 502 of 591 (85%) participants responded to acceptability questions, and 359 of 417 (86%) responded at week 52. Most reported the trial capsule easy or very easy to take. From eight sites, 16 participants were interviewed between 5 August 2020 and 19 November 2020. All described a positive experience, preferred once-daily morning dosing and found routine facilitated adherence. Participants valued individual responsibility for adherence, and involvement of the general practitioner in blood-pressure management. Most reported capsule size did not deter adherence but desired a smaller capsule. Participants described a preference for minimising number and dosage of medications, reduced capsule size, and once-daily morning dosing. These findings suggest a preference for single-pill combination therapy for blood pressure lowering.

Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure.

AIMS: Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure (HF) may provide insight into early mechanisms of HF pathogenesis. We examined risk factors associated with asymptomatic echocardiographic structural, systolic, and diastolic abnormalities, separately and in combination, and interactions between risk factors, in the prospective community-based SCReening Evaluation of the Evolution of New HF (SCREEN-HF) Study cohort of 3190 participants at increased risk of cardiovascular disease. METHODS AND RESULTS: Inclusion criteria were age ≥ 60 years with one or more of hypertension, diabetes, ischaemic heart disease, valvular heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction < 50%, or >mild valve abnormality. Structural, systolic, and diastolic echocardiographic abnormalities were defined according to the Atherosclerosis Risk in Communities study criteria, and risk factors for asymptomatic structural, systolic, and diastolic abnormalities were identified using logistic regression analysis. In multivariable analysis, increased body mass index (BMI), non-steroidal anti-inflammatory drug therapy, and alcohol intake were risk factors for isolated structural abnormality, whereas male gender, increased heart rate, atrial fibrillation (AF), angiotensin-converting enzyme inhibitor therapy, and obstructive sleep apnoea were associated with a lower risk. Moreover, male gender, smoking, increased systolic blood pressure, and physical inactivity were risk factors for isolated systolic abnormality, whereas increased pulse pressure and antihypertensive therapy were associated with a lower risk. Furthermore, increased age, blood pressure, amino-terminal pro-B-type natriuretic peptide level, and warfarin therapy (associated with AF) were risk factors for isolated diastolic abnormality, whereas increased heart rate and triglyceride level (associated with BMI) were associated with a lower risk. The association of increased heart rate with lower risk of structural and diastolic abnormalities was independent of ß-blocker therapy. Interactions between risk factors differed for structural, systolic, and diastolic abnormalities. CONCLUSIONS: The different risk factors for asymptomatic structural, systolic, and diastolic abnormalities that predict symptomatic HF, and the interactions between risk factors, illustrate how these structural, systolic, and diastolic abnormalities represent unique trajectories that lead to symptomatic HF. Improved understanding of these trajectories may assist in the design of HF prevention strategies.

An electronic decision support-based complex intervention to improve management of cardiovascular risk in primary health care: a cluster randomised trial (INTEGRATE).

OBJECTIVES: To determine whether a multifaceted primary health care intervention better controlled cardiovascular disease (CVD) risk factors in patients with high risk of CVD than usual care. DESIGN, SETTING: Parallel arm, cluster randomised trial in 71 Australian general practices, 5 December 2016 - 13 September 2019. PARTICIPANTS: General practices that predominantly used an electronic medical record system compatible with the HealthTracker electronic decision support tool, and willing to implement all components of the INTEGRATE intervention. INTERVENTION: Electronic point-of-care decision support for general practices; combination cardiovascular medications (polypills); and a pharmacy-based medication adherence program. MAIN OUTCOME MEASURES: Proportion of patients with high CVD risk not on an optimal preventive medication regimen at baseline who had achieved both blood pressure and low-density lipoprotein (LDL) cholesterol goals at study end. RESULTS: After a median 15 months' follow-up, primary outcome data were available for 4477 of 7165 patients in the primary outcome cohort (62%). The proportion of patients who achieved both treatment targets was similar in the intervention (423 of 2156; 19.6%) and control groups (466 of 2321; 20.1%; relative risk, 1.06; 95% CI, 0.85-1.32). Further, no statistically significant differences were found for a number of secondary outcomes, including risk factor screening, preventive medication prescribing, and risk factor levels. Use of intervention components was low; it was highest for HealthTracker, used at least once for 347 of 3236 undertreated patients with high CVD risk (10.7%). CONCLUSIONS: Despite evidence for the efficacy of its individual components, the INTEGRATE intervention was not broadly implemented and did not improve CVD risk management in participating Australian general practices. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000233426 (prospective).

Kidney age - chronological age difference (KCD) score provides an age-adapted measure of kidney function.

BACKGROUND: Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual's kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors. METHODS: We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years. RESULTS: In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60-69 years, with similar sensitivities for men and women. CONCLUSIONS: In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women. TRIAL REGISTRATION: ClinicalTrials.gov NCT00400257 , NCT00604006 , and NCT01581827 .

Age-related longitudinal change in cardiac structure and function in adults at increased cardiovascular risk.

AIM: Heart failure (HF) incidence increases markedly with age. We examined age-associated longitudinal change in cardiac structure and function, and their prediction by age and cardiovascular disease (CVD) risk factors, in a community-based cohort aged ≥60 years at increased CVD risk but without HF. METHODS AND RESULTS: CVD risk factors were recorded in 3065 participants who underwent a baseline echocardiographic examination, of whom 2358 attended a follow-up examination 3.8 [median, inter-quartile range (IQR) 3.5, 4.2] years later. Median age was 71 (IQR 67, 76) years and 55% of participants were male. Age was associated with longitudinal increase in left ventricular (LV) mass index (LVMI); decrease in LV volumes; increase in LV ejection fraction; decrease in mitral annular systolic velocity; decrease in diastolic function (decreased mitral early diastolic annular velocity (e'); and increase in left atrial volume index, mitral peak early diastolic flow velocity (E)/e' ratio, and tricuspid regurgitant velocity (TRVmax ) in men and women, except for TRVmax in men). In multivariable analysis, longitudinal increase in LVMI was explained by CVD risk factors alone, whereas age, together with CVD risk factors, independently predicted longitudinal change in all other echocardiographic parameters. CVD risk factors were differentially associated with longitudinal change in different echocardiographic parameters. CONCLUSIONS: Whereas the increase in LVMI with age was explained by CVD risk factors alone, age, together with risk factors, independently predicted longitudinal change in all other echocardiographic parameters, providing evidence for age-specific mechanisms of change in cardiac structure and function as people age. Age-associated change in LVMI, LV volumes, and diastolic function resembled what might be expected for the evolution of HF with preserved ejection fraction. Given the differential association of different CVD risk factors with longitudinal change in different echocardiographic parameters, therapies aimed at attenuation of age-associated change in cardiac structure and function, and HF evolution, will likely need to address multiple CVD risk factors.

Age-specific diastolic dysfunction improves prediction of symptomatic heart failure by Stage B heart failure.

AIMS: We investigated whether addition of diastolic dysfunction (DD) and longitudinal strain (LS) to Stage B heart failure (SBHF) criteria (structural or systolic abnormality) improves prediction of symptomatic HF in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Both American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) criteria and age-specific Atherosclerosis Risk in Communities (ARIC) study criteria, for SBHF and DD, and ARIC criteria for abnormal LS, were examined. METHODS AND RESULTS: Inclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known HF, or ejection fraction <50% or >mild valve abnormality detected on previous echocardiography or other imaging. Echocardiography was performed in 3190 participants who were followed for a median of 3.9 (interquartile range: 3.4, 4.5) years after echocardiography. Symptomatic HF was diagnosed in 139 participants at a median of 3.1 (interquartile range: 2.1, 3.9) years after echocardiography. ARIC structural, systolic, and diastolic abnormalities predicted HF in univariate and multivariable proportional hazards analyses, whereas ASE/EACVI structural and systolic, but not diastolic, abnormalities predicted HF. ARIC and ASE/EACVI SBHF criteria predicted HF with sensitivities of 81% and 55%, specificities of 39% and 76%, and C statistics of 0.60 (95% confidence interval: 0.57, 0.64) and 0.66 (0.61, 0.71), respectively. Adding ARIC DD to SBHF increased sensitivity to 94% with specificity of 24% and C statistic of 0.59 (0.57, 0.61), whereas addition of ASE/EACVI DD to SBHF increased sensitivity to 97% but reduced specificity to 9% and the C statistic to 0.52 (0.50, 0.54, P < 0.0001). Addition of LS to ARIC or ASE/EACVI SBHF criteria had minimal impact on prediction of HF. CONCLUSIONS: Age-specific ARIC DD criteria, but not ASE/EACVI DD criteria, predicted symptomatic HF, and addition of age-specific ARIC DD criteria to ARIC SBHF criteria improved prediction of symptomatic HF in asymptomatic individuals with cardiovascular disease risk factors. Addition of LS to ASE/EACVI or ARIC SBHF criteria did not improve prediction of symptomatic HF.

Threshold body mass index and sex-specific waist circumference for increased risk of heart failure with preserved ejection fraction.

BACKGROUND: Body mass index †Deceased. (BMI) is a risk factor for heart failure with preserved ejection fraction (HFpEF). DESIGN: We investigated the threshold BMI and sex-specific waist circumference associated with increased HFpEF incidence in the SCReening Evaluation of the Evolution of New Heart Failure (SCREEN-HF) study, a cohort study of a community-based population at increased cardiovascular disease risk. METHODS: Inclusion criteria were age ≥60 years with one or more of self-reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, ejection fraction <50% or more than mild valve abnormality. Among 3847 SCREEN-HF participants, 73 were diagnosed with HFpEF at a median of 4.5 (interquartile range: 2.9-5.5) years after enrolment. RESULTS: HFpEF incidence rates were higher for BMI ≥27.5 kg/m2 than for BMI < 25 kg/m2, and for waist circumference >100 cm (men) or > 90 cm (women) than for waist circumference ≤94 cm (men) or ≤ 83 cm (women) in Poisson regression analysis. Semiparametric proportional hazards analyses confirmed these BMI and waist circumference thresholds, and exceeding these thresholds was associated with an attributable risk of HFpEF of 44-49%. CONCLUSIONS: Both central obesity and overweight were associated with increased HFpEF incidence. Although a randomised trial of weight control would be necessary to establish a causal relationship between obesity/overweight and HFpEF incidence, these data suggest that maintenance of BMI and waist circumference below these thresholds in a community similar to that of the SCREEN-HF cohort may reduce the HFpEF incidence rate by as much as 50%.

Prediction of incident heart failure by serum amino-terminal pro-B-type natriuretic peptide level in a community-based cohort.

AIMS: We investigated which serum amino-terminal pro-B-type-natriuretic peptide (NT-proBNP) levels inform heart failure (HF) risk in a community-based population at increased cardiovascular disease (CVD) risk. METHODS AND RESULTS: Inclusion criteria were age ≥ 60 years with one or more of self-reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction (EF) < 50%, or more than mild valve abnormality. NT-proBNP levels were measured in 3842 participants on enrolment. HF was diagnosed in 162 participants at a median of 4.5 (interquartile range 2.7-5.4) years after enrolment, 73 with HF with preserved EF (HFpEF), 53 with HF with reduced EF (HFrEF), and 36 with valvular HF (VHF). Areas under the receiver operating characteristic curve (AUC) for 5-year prediction of total HF were similar for NT-proBNP alone (0.79, 95% confidence interval 0.74-0.83) and a 7-parameter multivariable model (0.82, 0.77-0.86, P = 0.035). NT-proBNP cut-points of 11, 16, and 25 pmol/L for individuals aged 60-69, 70-79, and ≥ 80 years, respectively, achieved sensitivities > 76% and specificities of 47-69% for 5-year prediction of total HF in men and women in all three age groups. Sensitivities were ≥ 75% in most subgroups according to body mass index, estimated glomerular filtration rate, and the presence or absence of atrial fibrillation, pacemaker, or CVD, and for the prediction of HFpEF, HFrEF and VHF. CONCLUSION: Age-specific serum NT-proBNP levels inform prognosis, and hence therapeutic decisions, regarding HF risk in individuals at increased CVD risk.

Risk factors for incident heart failure with preserved or reduced ejection fraction, and valvular heart failure, in a community-based cohort.

Background: The lack of effective therapies for heart failure with preserved ejection fraction (HFpEF) reflects an incomplete understanding of its pathogenesis. Design: We analysed baseline risk factors for incident HFpEF, heart failure with reduced ejection fraction (HFrEF) and valvular heart failure (VHF) in a community-based cohort. Methods: We recruited 2101 men and 1746 women ≥60 years of age with hypertension, diabetes, ischaemic heart disease (IHD), abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, left ventricular ejection fraction <50% or valve abnormality >mild in severity. Median follow-up was 5.6 (IQR 4.6-6.3) years. Results: Median time to heart failure diagnosis in 162 participants was 4.5 (IQR 2.7-5.4) years, 73 with HFpEF, 53 with HFrEF and 36 with VHF. Baseline age and amino-terminal pro-B-type natriuretic peptide levels were associated with HFpEF, HFrEF and VHF. Pulse pressure, IHD, waist circumference, obstructive sleep apnoea and pacemaker were associated with HFpEF and HFrEF; atrial fibrillation (AF) and warfarin therapy were associated with HFpEF and VHF and peripheral vascular disease and low platelet count were associated with HFrEF and VHF. Additional risk factors for HFpEF were body mass index (BMI), hypertension, diabetes, renal dysfunction, low haemoglobin, white cell count and ß-blocker, statin, loop diuretic, non-steroidal anti-inflammatory and clopidogrel therapies, for HFrEF were male gender and cigarette smoking and for VHF were low diastolic blood pressure and alcohol intake. BMI, diabetes, low haemoglobin, white cell count and warfarin therapy were more strongly associated with HFpEF than HFrEF, whereas male gender and low platelet count were more strongly associated with HFrEF than HFpEF. Conclusions: Our data suggest a major role for BMI, hypertension, diabetes, renal dysfunction, and inflammation in HFpEF pathogenesis; strategies directed to prevention of these risk factors may prevent a sizeable proportion of HFpEF in the community. Trial registration number: NCT00400257, NCT00604006 and NCT01581827.

Risk factor management in a contemporary Australian population at increased cardiovascular disease risk.

BACKGROUND: Effective management of cardiovascular and chronic kidney disease risk factors offers longer, healthier lives and savings in healthcare. AIM: To examine risk factor management in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. METHODS: Inclusion criteria were age ≥ 60 years with one or more self-reported ischaemic or other heart diseases, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or cardiac abnormality on echocardiography or other imaging. Medical history, clinical examination, full blood examination and biochemistry (without lipids and glycated haemoglobin (HbA1c)) were performed for 3847 participants on enrolment, and blood pressure, lipids and HbA1c were measured 1-2 years after enrolment for 3203 participants. RESULTS: Despite 99% of 3294 participants with hypertension receiving antihypertensive medication, half had blood pressures >140/90 mmHg. Approximately 77% of participants were overweight or obese, with one third being obese. Additionally, 74% of participants at high cardiovascular disease risk had low-density lipoprotein cholesterol levels ≥2 mmol/L, one third of diabetic participants had HbA1c >7%, 22% had an estimated glomerular filtration rate < 60 mL/min/1.73m2 , and substantial proportions had under-utilisation of antiplatelet therapy and anticoagulation for atrial fibrillation and were physically inactive. CONCLUSIONS: This population demonstrated substantial potential to reduce cardiovascular and renal morbidity and mortality and healthcare costs through more effective management of modifiable risk factors.

SCReening Evaluation of the Evolution of New Heart Failure Study (SCREEN-HF): early detection of chronic heart failure in the workplace.

Objective The aim of the present study was to determine whether asymptomatic heart failure (HF) in the workplace is subject to the health worker effect, making screening using conventional risk factors combined with a cardiac biomarker, namely N-terminal pro B-type natriuretic peptide (NT-proBNP), as useful as in the general population. Methods Between June 2007 and December 2009 a 'well' population deemed at high risk for development of HF was identified through health insurance records. Blood was collected from volunteer participants for analysis of urea, electrolytes and creatinine, a full blood count and NT-proBNP. An echocardiogram was performed on selected participants based on high NT-proBNP concentrations. Results The mean left ventricular ejection fraction (LVEF) was significantly reduced in participants with the highest compared with the lowest NT-proBNP quintile. In multivariate analysis, log-transformed NT-proBNP was independently associated with impaired LVEF and with moderate to severe diastolic dysfunction after adjustment for age, sex, coronary artery disease, diabetes, hypertension and obesity. Conclusions A large burden of asymptomatic left ventricular dysfunction (AVLD) was observed in subjects aged 60 and over with plasma NT-proBNP in the top quintile that was independent of conventional risk factors and work status. HWE does not appear to operate in AVLD. NT-proBNP testing in a population with HF risk factors may cost-effectively identify those at greatest risk of developing HF in a working population and facilitate early diagnosis, treatment and maintenance of work capacity. What is known about the topic? Chronic heart failure (CHF) has several causes, the most common being hypertension and coronary ischaemia. CHF is a major health problem of increasing prevalence that severely impacts quality of life, shortens lives and reduces worker productivity. It is often not diagnosed early enough to take full advantage of ameliorating medication. What does this paper add? Population screening for CHF is not currently advocated. This may be because conventional risk factors must be used in combination and there is no useful biomarker available. Yet evidence (SOLVD (Studies of Left Ventricular Dysfunction trials) recommends early diagnosis. We believe the work place is an area of potential screening where there is little supporting evidence. This paper provides evidence that the biomarker NT-proBNP is a useful new tool that improves cost-effectiveness of screening in a selected population. Specifically, the paper recommends CHF screening in the population with the highest potential health gain (i.e. the working population) by the sector with the highest economic gain (i.e. employers). What are the implications for practitioners? The paper presents important health screening recommendations for medical and health and safety practitioners within a selected population of workers. We feel practitioners should consider screening for incipient heart failure, particularly within Australia's working population, to save lives, provide economic benefit and extend working longevity.

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial.

BACKGROUND: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. METHODS: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. DISCUSSION: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000233426.

A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk.

BACKGROUND: Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications. METHODS: We conducted a randomized, open-label trial involving 623 participants from Australian general practices. Participants had established CVD or an estimated five-year CVD risk of ≥15%, with indications for antiplatelet, statin and ≥2 blood pressure lowering drugs ('combination treatment'). Participants randomized to the 'polypill-based strategy' received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to 'usual care' continued with separate medications and doses as prescribed by their doctor. Primary outcomes were self-reported combination treatment use, systolic blood pressure and total cholesterol. RESULTS: After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p < 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26). At study end, 17% and 67% of participants in polypill and usual care groups, respectively, were taking atorvastatin or rosuvastatin. CONCLUSION: Provision of a polypill improved self-reported use of indicated preventive treatments. The lack of differences in blood pressure and cholesterol may reflect limited study power, although for cholesterol, improved statin use in the polypill group counter-balanced use of more potent statins with usual care.

Amino-terminal-pro-B-type natriuretic peptide levels and low diastolic blood pressure: potential relevance to the diastolic J-curve.

BACKGROUND: There is debate whether the J-curve relationship between cardiac event risk and DBP is because of inherent cardiac risk or is a consequence of blood pressure (BP) lowering therapy. METHODS: We examined the association between the cardiovascular risk marker amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) and DBP in 1781 women and 2211 men aged at least 60 years with one or more cardiovascular risk factors; exclusion criteria were known heart failure or cardiac abnormality on a cardiac imaging study. RESULTS: The lowest median serum NT-proBNP levels were for DBP 85-89 mmHg for both women and men. DBP less than 70 mmHg in women and less than 80 mmHg in men was associated with higher NT-proBNP levels than the levels at DBP 85-89 mmHg, and this relationship was present for those with SBP equal to or less than 140 and SBP greater than 140 mmHg. In conditional logistic regression models, the association of elevated NT-proBNP levels with low DBP in women was no longer statistically significant after adjustment for age, ischaemic heart disease (IHD), pulse rate, atrial fibrillation, haemoglobin and glomerular filtration rate, whereas the association in men was no longer statistically significant after adjustment for age and IHD. By contrast, the association between elevated NT-proBNP levels and low DBP remained statistically significant after adjustment for the number of antihypertensive drug classes alone or together with all antihypertensive drugs, including ß-blocker therapy. CONCLUSION: There was a J-curve relationship between the cardiovascular risk marker NT-proBNP and DBP that was explained by the clinical variables and not by the BP-lowering therapy.

NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular dysfunction: results of the SCReening Evaluation of the Evolution of New Heart Failure study (SCREEN-HF).

BACKGROUND: We assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP). METHODS AND RESULTS: 3550 subjects at high risk for incident HF (≥60 years plus ≥1 HF risk factor), but without pre-existing HF or left ventricular dysfunction, were recruited. Anthropomorphic data, medical history and blood for NT-proBNP were collected. Participants at highest risk (n = 664) (NT-proBNP highest quintile; >30.0 pmol/L) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography. Participants in the highest NT-proBNP quintile, compared to the lowest, were older (74 years vs. 67 years; p < 0.001) and more likely to have coronary artery disease, stroke or renal impairment. In the top NT-proBNP quintile (n = 664), left ventricular systolic impairment was observed in 6.6% (95% CI: 4 to 8%) of participants and was associated with male gender, coronary artery disease, hypertension and NT-proBNP. At least moderate diastolic dysfunction was observed in 24% (95% CI 20 to 27%) of participants and was associated with diabetes and NT-proBNP. In this high risk population, NT-proBNP was associated with left ventricular systolic impairment (p < 0.001) and moderate to severe diastolic dysfunction (p < 0.001) after adjustment for age, gender, coronary artery disease, diabetes, hypertension and obesity. CONCLUSION: A high burden of ventricular dysfunction was observed in this high risk group. Combining NT-proBNP and HF risk factors may identify those with ventricular dysfunction. This would allow resources to be focused on those at greatest risk of progression to overt HF.

N-terminal B-type natriuretic peptide and the association with left ventricular diastolic function in a population at high risk of incident heart failure: results of the SCReening Evaluationof the Evolution of New-Heart Failure Study (SCREEN-HF).

AIMS: Impaired diastolic function is associated with increased morbidity and mortality, but antecedents and predictors of progression to heart failure (HF) are not well understood. We examined associations between NT-proBNP, HF risk factors, and diastolic function in a population at high risk for incident HF. METHODS AND RESULTS: A total of 3550 subjects at high risk for incident HF (≥60 years plus ≥1 HF risk factor), but without pre-existing HF or LV dysfunction were recruited. Participants at highest risk (n = 664) (NT-proBNP in the highest quintile >254 pg/mL) underwent echocardiography. Moderate or severe diastolic dysfunction was observed in 25% [95% confidence interval (CI) 21-29%] of participants. Age (P = 0.001), male gender (P = 0.03), diabetes (P = 0.03), and NT-proBNP (P = 0.002) were associated with severity of diastolic dysfunction after adjustment for HF risk factors and LVEF. In regression analysis, log-transformed NT-proBNP was also associated with LV mass index (P = 0.05), left atrial size (P < 0.0001), and Doppler ratio of the mitral valve E/e' (P = 0.001). Multiple HF risk factors were present in the majority of participants (>70%), but no association was observed between diastolic dysfunction and the number of risk factors reported (P = 0.3). CONCLUSION: Diastolic dysfunction was observed in one in four of these high risk subjects (≥ 60 years, HF risk factor, NT-proBNP >254 pg/mL). NT-proBNP, age and diabetes were strongly associated with severity of diastolic dysfunction, whereas other HF risk factors and LVEF were not. More targeted surveillance using a combination of risk factors and biomarkers may improve identification of those at great risk of incident HF.

Ankle-Brachial Index determination and peripheral arterial disease diagnosis by an oscillometric blood pressure device in primary care: validation and diagnostic accuracy study.

OBJECTIVES: To determine the level of agreement between a 'conventional' Ankle-Brachial Index (ABI) measurement (using Doppler and mercury sphygmomanometer taken by a research nurse) and a 'pragmatic' ABI measure (using an oscillometric device taken by a practice nurse) in primary care. To ascertain the utility of a pragmatic ABI measure for the diagnosis of peripheral arterial disease (PAD) in primary care. DESIGN: Cross-sectional validation and diagnostic accuracy study. Descriptive analyses were used to investigate the agreement between the two procedures using the Bland and Altman method to determine whether the correlation between ABI readings varied systematically. Diagnostic accuracy was assessed via sensitivity, specificity, accuracy, likelihood ratios, positive and negative predictive values, with ABI readings dichotomised and Receiver Operating Curve analysis using both univariable and multivariable logistic regression. SETTING: Primary care in metropolitan and rural Victoria, Australia between October 2009 and November 2010. PARTICIPANTS: 250 persons with cardiovascular disease (CVD) or at high risk (three or more risk factors) of CVD. RESULTS: Despite a strong association between the two method's measurements of ABI there was poor agreement with 95% of readings within ±0.4 of the 0.9 ABI cut point. The multivariable C statistic of diagnosis of PAD was 0.89. Other diagnostic measures were sensitivity 62%, specificity 92%, positive predictive value 67%, negative predictive value 90%, accuracy 85%, positive likelihood ratio 7.3 and the negative likelihood ratio 0.42. CONCLUSIONS: Oscillometric ABI measures by primary care nurses on a population with a 22% prevalence of PAD lacked sufficient agreement with conventional measures to be recommended for routine diagnosis of PAD. This pragmatic method may however be used as a screening tool high-risk and overt CVD patients in primary care as it can reliably exclude the condition.

Outcomes from the REACH Registry for Australian general practice patients with or at high risk of atherothrombosis.

OBJECTIVE: To report on 1-year cardiovascular (CV) event rates in patients with established cardiovascular disease (CVD) or with multiple cardiovascular risk factors. DESIGN, PATIENTS AND SETTING: Prospective cohort study of 2873 patients at high risk of atherothrombosis based on the presence of multiple risk factors and overt coronary artery disease (CAD), cerebrovascular disease (CerVD) or peripheral arterial disease (PAD) presenting to 273 Australian general practitioners; this study was conducted as part of the international REACH Registry. MAIN OUTCOME MEASURES: One-year rates of cardiovascular death, myocardial infarction, stroke, and hospitalisation for cardiovascular procedures. RESULTS: The cardiovascular death rate at 1 year was 1.4%. The combined cardiovascular death, non-fatal MI, stroke and hospitalisation rate for vascular disease affecting one location at 1 year was 11%. Even for patients with no overt disease, but with multiple risk factors, the 1-year combined event rate was 4.2%. The highest combined event rate was in patients with PAD (21.0%), and in patients with atherothrombotic disease identified in all three locations (coronary arteries, cerebrovascular system and peripheral arteries) at 39%. CONCLUSION: The rate of clinical events in community-based patients with stable atherothrombotic disease increases dramatically with the severity of disease and the number of vascular beds involved. Where disease was evident in all three locations, and for patients with PAD alone, the 1-year risk of cardiovascular events was substantially increased. Poor adherence to statin therapy in the secondary preventive setting is a major treatment gap that needs to be closed; the influences of obesity and diabetes warrant further investigation.

Drug treatment and cost of cardiovascular disease in Australia.

Australia's Pharmaceutical Benefits Scheme supports the use of effective drugs for the prevention and control of cardiovascular risk factors. However, there are little data available describing per person costs of medication in primary prevention and secondary prevention in the community. We aim to understand annual expenditure on cardiovascular medicines according to the level and extent of cardiovascular disease, using participants enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) registry. 2873 participants were recruited into the REACH registry through 273 Australian general practices. Cardiovascular medicines review was undertaken at baseline. Average weighted costs of medications were estimated using government-reimbursed prices. Annual costs were stratified by disease extent and location. The annual mean cost of pharmaceuticals per person was 1307 AU dollars. The average reported medicine use per person across all states and participants groups varied significantly. Participants with cerebrovascular or peripheral arterial disease were prescribed less cardiovascular medication than those with coronary artery disease (CAD) (mean number of drugs 3.5 vs. 4.5, P < 0.0001) and (3.6 vs. 4.5, P < 0.0001), while those with risk factor alone had the same medication use as those with CAD (mean number 4.5). Medication use was lower in Western Australia in comparison to eastern States. Participants with existing cerebrovascular disease and peripheral vascular disease receive less preventive therapy than those with CAD or even risk factors alone. This observation is consistent across all mainland states. Given the evidence of the effectiveness and cost-effectiveness of treating all types of vascular diseases, the present study suggests that there is scope to improve the treatment of these high-risk participants in Australia.

Australians at risk: management of cardiovascular risk factors in the REACH Registry.

BACKGROUND AND RATIONAL: Atherothrombosis is the leading cause of cardiovascular morbidity and mortality in Australia and around the world. The evidence base for appropriate management of these subjects has increased over the past decade through the conduct of randomised controlled trials. However little is known of the translation of evidence into clinical practice in terms of current management practice and risk factor control in high-risk patients in Australia. METHODS: As part of the international REACH (Reduction of Atherothrombosis for Continued Health, protocol number C 8903) Registry, subjects at high risk of atherothrombosis based on the presence of multiple risk factors or overt coronary artery (CAD), cerebrovascular (CVD) or peripheral arterial disease (PAD) underwent a cardiovascular risk factor review. Demographic data and current medication management was also assessed. The subjects were recruited entirely through Australian general practice. RESULTS: Globally 67,888 patients were involved in the REACH registry of whom 2783 were recruited from 273 general practitioners around Australia. In comparison to the global population sample the Australian cohort was older (72 years versus 68 years) and had a lower prevalence of current smoking (7% versus 14%). Seventy-three percent of the Australian cohort had CAD and 15% had vascular disease in more than one location. Seventy-four percent of the cohort was either overweight or obese. Despite the widespread use of antihypertensive and lipid lowering therapy, half of the total group had a blood pressure recorded as >or=140/90 mmHg and 24% of the cohort had a total cholesterol level >5.2 mmol/L. CONCLUSION: The REACH registry offers the opportunity to provide a better understanding of the management of cardiovascular risk factors in patients at high-risk of atherothrombosis in Australia. Reducing the high rates of overweight and obesity and increasing the proportion of patients achieving therapeutic targets should remain priority areas in the management of this group of high-risk patients.