Quality of life and associations with health-related behaviours among older adults with increased cardiovascular risk.

BACKGROUND AND AIMS: A better understanding of the relationship between cardiovascular disease risk factors and quality of life (QoL) in older age is needed to inform development of risk reduction strategies. This cross-sectional study investigated the association of QoL with health-related behaviours in older adults at risk of heart failure. METHODS AND RESULTS: Older adults (N = 328) at risk of heart failure residing in Melbourne, Australia, provided data on QoL and health-related behaviours including physical activity, diet, smoking and alcohol consumption. Multiple linear regression modelling was used to examine associations between health-related behaviours, QoL and its constituent domains. After adjustment for age, gender, body mass index and comorbidities, current smoking was found to have a negative association with the mental component score (MCS) of QoL (ß = -0.174, p ≤ 0.01), with a positive association seen between MCS and physical activity (ß = 0.130, p = 0.01). Current alcohol use had a positive association with the physical component score (PCS) (ß = 0.120, p = 0.02) and saturated fat intake consumption had a negative association with the physical functioning domain of QoL (ß = -0.105, p = 0.03) but was not associated with either PCS or MCS. CONCLUSION: Engagement of older adults at increased cardiovascular risk with behavioural risk factor modification using QoL as a driver of change may offer new opportunities to promote healthy ageing. Development of such strategies should consider that for some behaviours which are cardiovascular risk factors (alcohol intake, in particular), the positive association to QoL is complicated and needs further deliberation.

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 .

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.

Therapeutic modulation of tissue kallikrein expression.

The kallikrein kinin system has cardioprotective actions and mediates in part the cardioprotection produced by angiotensin converting enzyme inhibitors and angiotensin type 1 receptor blockers. Additional approaches to exploit the cardioprotective effects of the kallikrein kinin system include the administration of tissue kallikrein and kinin receptor agonists. The renin inhibitor aliskiren was recently shown to increase cardiac tissue kallikrein expression and bradykinin levels, and to reduce myocardial ischemia-reperfusion injury by bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanisms. Thus, aliskiren represents a prototype drug for the modulation of tissue kallikrein expression for therapeutic benefit.

Can cardiovascular disease guidelines that advise treatment decisions based on absolute risk be improved?

BACKGROUND: Cardiovascular disease (CVD) will remain the predominant cause of death and a major cause of morbidity for the foreseeable future. Consequently, CVD prevention offers the greatest potential for the prevention of premature mortality and the compression of morbidity. DISCUSSION: The 2013 guidelines of the American College of Cardiology and the American Heart Association expand the eligibility for CVD preventive treatment based on the calculated 10-year CVD risk derived from the pooled cohort equation to all persons who have a 10-year risk of CVD of ≥7.5% as estimated by the pooled cohort equation. Previous analyses show that the use of a uniform 10-year risk threshold of 7.5% for all ages disadvantages younger individuals for whom preventive therapy has most to offer. Here I show that reducing the threshold to 3% in younger adults (women aged <66 years and men aged <56 years) will substantially increase the number of cardiovascular events prevented at a similar number needed to treat to prevent one event. Importantly, this increase in cardiovascular event prevention will occur in individuals with greater life expectancy. CONCLUSION: Reducing the threshold 10-year risk of CVD derived from the pooled cohort equation for CVD preventive treatment to 3% in younger adults (women aged <66 years and men aged <56 years) will more effectively prevent premature mortality and compress morbidity to an older age.

Prorenin stimulates a pro-angiogenic and pro-inflammatory response in retinal endothelial cells and an M1 phenotype in retinal microglia.

Angiogenesis and inflammation are causative factors in the development of neovascular retinopathies. These processes involve the retinal endothelium and the retinal immune cells, microglia. The renin-angiotensin system contributes to retinal injury via the actions of the type 1 angiotensin receptor (AT1R). However, it has been suggested that prorenin, the initiator of the renin-angiotensin system cascade, influences retinal injury independently from the AT1R. We evaluated whether prorenin induced a pro-angiogenic and pro-inflammatory response in retinal endothelial cells and a pro-inflammatory phenotype in retinal microglia. Primary cultures of retinal endothelial cells and microglia were studied. Rat recombinant prorenin (2 nmol/L) stimulated the proliferation and tubulogenesis of retinal endothelial cells; it increased the levels of pro-angiogenic factors, vascular endothelial growth factor, angiopoietin-1, and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains, and pro-inflammatory factors, intercellular adhesion molecule-1 and monocyte chemoattractant protein-1, relative to the controls. The messenger RNA levels of the (pro)renin receptor were also increased. These effects occurred in the presence of the AT1R blocker candesartan (10 µmol/L) and the renin inhibitor aliskiren (10 µmol/L). Microglia, which express the (pro)renin receptor, elicited an activated phenotype when exposed to prorenin, which was characterized by increased levels of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, tumour necrosis factor-α, interleukin-6, and interleukin-1ß and by decreased levels of interleukin-10 and arginase-1 relative to controls. Candesartan did not influence the effects of prorenin on retinal microglia. In conclusion, prorenin has distinct pro-angiogenic and pro-inflammatory effects on retinal cells that are independent of the AT1R, indicating the potential importance of prorenin in retinopathy.

The operating surgeon is an independent predictor of chest tube drainage following cardiac surgery.

OBJECTIVES: Bleeding into the chest is a major cause of blood transfusion and adverse outcomes following cardiac surgery. The authors investigated predictors of bleeding following cardiac surgery to identify potentially correctable factors. DESIGN: Data were retrieved from the medical records of patients undergoing cardiac surgery over the period of 2002 to 2008. Multivariate analysis was used to identify the independent predictors of chest tube drainage. SETTING: Tertiary hospital. PARTICIPANTS: Two thousand five hundred seventy-five patients. INTERVENTIONS: Cardiac surgery. RESULTS: The individual operating surgeon was independently associated with the extent of chest tube drainage. Other independent factors included internal mammary artery grafting, cardiopulmonary bypass time, urgency of surgery, tricuspid valve surgery, redo surgery, left ventricular impairment, male gender, lower body mass index and higher preoperative hemoglobin levels. Both a history of diabetes and administration of aprotinin were associated with reduced levels of chest tube drainage. CONCLUSIONS: The individual operating surgeon was an independent predictor of the extent of chest tube drainage. Attention to surgeon-specific factors offers the possibility of reduced bleeding, fewer transfusions, and improved patient outcomes.

The association of blood transfusion with mortality after cardiac surgery: cause or confounding? (CME).

BACKGROUND: Bleeding into the chest is a life-threatening complication of cardiac surgery. Blood transfusion has been implicated as an important cause of harm associated with bleeding, based largely on studies demonstrating an independent association between transfusion and mortality. These studies did not, however, consider the possibility that bleeding may in itself be harmful, inasmuch as drains are inefficient at clearing blood from the chest and retained blood may compromise cardiac and lung function. STUDY DESIGN AND METHODS: We undertook a multivariate logistic regression analysis of the risk factors associated with mortality in 2599 consecutive patients undergoing cardiac surgery. Unlike previous studies the risk factors examined included the volume of chest tube drainage at 24 hours. A stratified analysis was also undertaken that compared the adjusted risk of death for patients exposed or not exposed to a postoperative blood transfusion. RESULTS: Blood transfusion was not an independent predictor of mortality (p=0.4). Chest tube drainage was the strongest independent predictor of mortality (p<0.001). In the stratified analysis, chest tube drainage remained an independent predictor of mortality for patients not exposed to a blood transfusion (p<0.01). Furthermore, the risk of death of these patients was no different from patients exposed to a blood transfusion (p=0.7 for interaction). CONCLUSIONS: Our results argue that for patients undergoing cardiac surgery bleeding contributes to mortality through mechanisms unrelated to blood transfusion.

Do intravenous and subcutaneous angiotensin II increase blood pressure by different mechanisms?

Angiotensin (Ang) II plays a key role in blood pressure regulation. Mechanisms of the pressor effect of chronic intravenous AngII administration include vasoconstriction, stimulation of the sympathetic nervous system and aldosterone production, as well as direct effects on renal excretion of sodium and water. Chronic AngII administration by subcutaneous minipump at doses higher than required to increase blood pressure by the intravenous route has identified additional pressor mechanisms, including the immune system, cytokines and matrix metalloproteinases. However, pressor doses of subcutaneous AngII may exceed the angiotensinogen synthesis rate and produce inflammation, fibrosis and necrosis of skin overlying the minipump. Evidence that chronic subcutaneous and intravenous AngII increase blood pressure by different mechanisms includes the prevention of the pressor effects of subcutaneous, but not intravenous, AngII by angiotensin-converting enzyme inhibition. Furthermore, low doses of subcutaneous AngII reduce blood pressure of female, but not male, rodents and higher doses are less pressor in females than in males, whereas intravenous AngII is equally pressor in males and females. Pressor doses of chronic subcutaneous AngII produce greater weight loss, anorexia and reduced kidney weight and cause greater vascular, cardiac and renal pathology than equally pressor doses of chronic intravenous AngII. The different effects of chronic intravenous and subcutaneous AngII suggest that these two models of hypertension give different information and may differ in their relevance to blood pressure regulation in physiological and pathological states such as hypertension in humans.

Prediction of cardiovascular death and non-fatal cardiovascular events by the Kidney age-Chronological age Difference (KCD) score in men and women of different ages in a community-based cohort.

OBJECTIVE: We examined the utility of the Kidney age-Chronological age Difference (KCD) score, an age-adapted measure of kidney function, to identify increased cardiovascular (CV) death or non-fatal CV event risk in participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), a community-based cohort aged 23-95 years. DESIGN: Cohort study. SETTING: Community. PARTICIPANTS: 11205 randomly selected participants from urban and nonurban areas across Australia. OUTCOME MEASURES: Mortality status and underlying and contributory causes of death obtained from the Australian National Death Index, and non-fatal CV events from adjudicated hospital records. The association of CV death or non-fatal CV event risk with KCD score was examined using penalised spline curve analysis. RESULTS: Of 11 180 participants with serum creatinine measurement at baseline and 5-year outcome data, there were 308 CV deaths or non-fatal CV events after 5 years. Penalised spline curve analysis showed similar progressive increase in CV death or non-fatal CV event risk with increasing KCD score in men and women, and participants aged <50 years to ≥80 years. Receiver operating characteristic curve analysis showed optimal discrimination at a KCD score ≥20 years (KCD20) for all participants. Among 148 participants aged<70 years with CV death or non-fatal CV event, KCD20 identified 24 (16%) participants, whereas estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 identified 8 (5%) participants (p=0.0001), with specificities of 95% and 99%, respectively (p<0.0001). CONCLUSION: KCD20 predicted CV death or non-fatal CV event risk similarly in men and women of different ages in this population-based cohort. The higher sensitivity for prediction of CV death or non-fatal CV event risk in participants aged <70 years by KCD20 than by eGFR <60 mL/min/1.73 m2 offers opportunity for earlier renoprotective therapy in individuals with eGFR-associated increased CV death or non-fatal CV event risk.

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.

AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance.

The AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that regulates appetite and fuel metabolism. We have generated AMPK beta1(-/-) mice on a C57Bl/6 background that are viable, fertile, survived greater than 2 years, and display no visible brain developmental defects. These mice have a 90% reduction in hepatic AMPK activity due to loss of the catalytic alpha subunits, with modest reductions of activity detected in the hypothalamus and white adipose tissue and no change in skeletal muscle or heart. On a low fat or an obesity-inducing high fat diet, beta1(-/-) mice had reduced food intake, reduced adiposity, and reduced total body mass. Metabolic rate, physical activity, adipose tissue lipolysis, and lipogenesis were similar to wild type littermates. The reduced appetite and body mass of beta1(-/-) mice were associated with protection from high fat diet-induced hyperinsulinemia, hepatic steatosis, and insulin resistance. We demonstrate that the loss of beta1 reduces food intake and protects against the deleterious effects of an obesity-inducing diet.

Whole body deletion of AMP-activated protein kinase {beta}2 reduces muscle AMPK activity and exercise capacity.

AMP-activated protein kinase (AMPK) ß subunits (ß1 and ß2) provide scaffolds for binding α and γ subunits and contain a carbohydrate-binding module important for regulating enzyme activity. We generated C57Bl/6 mice with germline deletion of AMPK ß2 (ß2 KO) and examined AMPK expression and activity, exercise capacity, metabolic control during muscle contractions, aminoimidazole carboxamide ribonucleotide (AICAR) sensitivity, and susceptibility to obesity-induced insulin resistance. We find that ß2 KO mice are viable and breed normally. ß2 KO mice had a reduction in skeletal muscle AMPK α1 and α2 expression despite up-regulation of the ß1 isoform. Heart AMPK α2 expression was also reduced but this did not affect resting AMPK α1 or α2 activities. AMPK α1 and α2 activities were not changed in liver, fat, or hypothalamus. AICAR-stimulated glucose uptake but not fatty acid oxidation was impaired in ß2 KO mice. During treadmill running ß2 KO mice had reduced maximal and endurance exercise capacity, which was associated with lower muscle and heart AMPK activity and reduced levels of muscle and liver glycogen. Reductions in exercise capacity of ß2 KO mice were not due to lower muscle mitochondrial content or defects in contraction-stimulated glucose uptake or fatty acid oxidation. When challenged with a high-fat diet ß2 KO mice gained more weight and were more susceptible to the development of hyperinsulinemia and glucose intolerance. In summary these data show that deletion of AMPK ß2 reduces AMPK activity in skeletal muscle resulting in impaired exercise capacity and the worsening of diet-induced obesity and glucose intolerance.

Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease.

BACKGROUND: Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs) in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE) in men with coronary artery disease. METHODS: We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. RESULTS: All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E'), consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red), or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyl)lysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. CONCLUSIONS: Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the myocardial microvascular structure, or increased myocardial expression of Nε-(carboxymethyl)lysine or RAGE. These findings suggest that the increased myocardial fibrosis and AGE expression, cardiomyocyte hypertrophy, and altered microvasculature structure described in diabetic heart disease were a consequence, rather than an initiating cause, of cardiac dysfunction.

Aliskiren increases bradykinin and tissue kallikrein mRNA levels in the heart.

1. Aliskiren is a renin inhibitor with an IC(50) of 0.6 nmol/L for human renin, 4.5 nmol/L for mouse renin and 80 nmol/L for rat renin. 2. In the present study, we compared the effects of aliskiren (10 mg/kg per day), the angiotensin-converting enzyme inhibitor perindopril (0.2 mg/kg per day) and their combination on angiotensin and bradykinin peptides in female heterozygous (mRen-2)27 rats, transgenic for the mouse renin gene. 3. All three treatments produced similar reductions in systolic blood pressure, heart weight and plasma aldosterone levels and reduced angiotensin II levels in lung, but only perindopril and the combination reduced angiotensin II levels in kidney of (mRen-2)27 rats. In contrast, aliskiren and the combination, but not perindopril alone, increased cardiac bradykinin levels. Aliskiren increased immunostaining for tissue kallikrein in the heart and reduced cardiac fibrosis. 4. We investigated the mechanism underlying the increase in bradykinin levels following aliskiren treatment in Sprague-Dawley rats, in which aliskiren has a lower potency for renin inhibition. Aliskiren (10 mg/kg per day) reduced renal angiotensin levels within 24 h, but treatment for > 24 h was required to increase cardiac bradykinin levels. Moreover, 3 mg/kg per day aliskiren increased cardiac bradykinin levels, but did not reduce renal angiotensin levels. Aliskiren did not potentiate the hypotensive effects of bradykinin; however, it increased tissue kallikrein, but not plasma kallikrein, mRNA levels in the heart. 5. These data demonstrate that the aliskiren-induced increase in cardiac bradykinin levels is independent of renin inhibition and changes in bradykinin metabolism, but is associated with increased tissue kallikrein gene expression.

Mis-reporting of energy intake among older Australian adults: Prevalence, characteristics, and associations with quality of life.

OBJECTIVES: Mis-reporting is common in dietary assessment, leading to misinterpretation of disease risk and could be important in older adults with increased chronic disease risk. This study investigated the prevalence and characteristics of mis-reporting among older adults and its association with health outcomes including quality of life (QoL). METHODS: The study was conducted in 335 community-dwelling older adults at increased risk for cardiovascular disease, participating in the SCReening Evaluation of the Evolution of New Heart Failure Study dietary substudy. Diet was assessed using 4-day weighed food diaries, QoL measured through Short Form 36, and physical activity assessed using the European Prospective Investigation into Cancer and Nutrition physical activity questionnaire. Dietary mis-reporting was defined based on Goldberg cutoffs, using individual physical activity levels. Odds ratios were determined to establish associations between mis-reporting and health outcomes. RESULTS: The prevalence of mis-reporting among older adults was 49.3%, with 44.5% of women mis-reporting their energy intake. The study found under-reporting of energy to be associated with body mass index, specifically being overweight (odds ratio: 3.08; 95% confidence interval [CI], 1.54-6.15) and obese (odds ratio: 6.60; 95% CI, 3.05-4.26), as well as physical inactivity (odds ratio: 0.24; 95% CI, 0.14-0.43). Only physical inactivity predicted over-reporting of dietary intake (odds ratio: 7.52; 95% CI, 1.57-36.0). CONCLUSIONS: Dietary under-reporting was associated with being overweight, obese, and physically inactive in addition to the absence of comorbidities, reinforcing the need for further research in older adults to factor in dietary mis-reporting for meaningful diet-disease relationship analyses.