Objective: The role of aldosterone in hypertension was generally considered in the context of primary hyperaldosteronism, an uncommon condition (less than 2% in the hypertensive population). However, based on an increased ambulant aldosterone-to-renin ratio (ARR), a marker of inappropriate aldosterone activity, the prevalence of primary hyperaldosteronism in the hypertensive population may be as high as 10% to 15%. There is increasing evidence to suggest a BP-independent effect of aldosterone on left ventricular structure, increased collagen deposition with fibrosis, diastolic dysfunction and arterial stiffness. We hypothesized that aldosterone and renin will be associated with microvascular and macrovascular alterations in never treated essential hypertension. Design and method: We prospectively studied newly diagnosed, untreated essential hypertensive and normotensive subjects (n = 1482, 47% females, mean age 51 ± 0.77, SEM). Pulse wave velocity (PWV), augmentation index (AIx), aortic systolic BP and pulse pressure amplification were measured with applanation tonometry(SphygmoCor). Albumin-creatinine ratio, urine sodium and potassium concentrations were determined from spot urine samples. Laboratory tests included serum creatinine and clearance, plasma renin activity, serum aldosterone, and high-sensitivity C-reactive protein(hs-CRP). Aldosterone to renin ratio(ARR) was divided into tertiles. Results were analysed using JMP Pro(Version 13, SAS for Windows). The patients gave informed consent and the study had Institutional ethics committee permission. Results: The top ARR tertile was associated with the highest levels of brachial BP, aortic systolic BP, AIx, pulse pressure amplification and PWV(P < 0.001 for all). Stepwise regression analysis showed that the positive association between PWV and increasing ARR tertiles remained significant after adjustment for BP, age and other potential confounders(R2 = 0.39, p < 0.05). The top ARR tertile was also associated with high potassium and low sodium urinary excretion, high ACR, low creatinine clearance and high hs-CRP (All p < 0.01). Conclusions: In untreated hypertensive subjects with mild to moderate hypertension, there are significant interactions between ARR and indices of microvascular and macrovascular damage. Our findings indicate that aldosterone and renin adversely modulate microvascular and macrovascular function very early in the evolution of hypertension. While aldosterone antagonism is recommended currently for treatment-resistant hypertension, our findings suggest that it should be initiated early in hypertension.

Cigarette smoking is the commonest modifiable risk factor for coronary artery disease (CAD) and vascular inflammation may play an important role in the pathogenesis. However, the presence of confounding factors, particularly age and gender, makes it difficult to interpret vascular effects of smoking

Introduction Arterial stiffness and wave reflection are independent prognosticators of cardiovascular morbidity and mortality. There are two types off arteries in the body; elastic and muscular. The elastic arteries receive the blood directly from the heart while the muscular arteries distribute the blood to various organs of the body. The elasticity of the major arteries decreases with age and therefore may play a key role in the development and control of hypertension and subsequently the choice of drug therapy. The aim of the study is to evaluate the effects of the amlodipine, on arterial stiffness in essential hypertension, compared to hydrochlorothiazide. Methodology We randomised 24 hypertensive patients hypertension (clinic blood pressure (BP) u003e 140/90 mmHg and ambulatory u003e135/85 mmHg) to amlodipine 5 mg or hydrochlorothiazide 12.5 mgs in a single blind parallel group study for one month and measured aortic pulse wave velocity (PWV) and augmentation index (AIx) at baseline and one month after treatment. The patients were studied fasting, having abstained from smoking, caffeinated beverages and alcohol 12 h prior to the measurements. Brachial BP and heart rate (Omron), pulse wave velocity (PWV, Complior) and augmentation index (AIx, SphymoCor), a measure of wave reflection, were measured in the supine position after a rest of 15 min. Results were analysed with JMP (SAS for Windows) using Wilcoxon-Rank Sums test and ANOVA. Results are expressed as mean ± SEM, p  Results Both drugs produced a similar reduction in brachial BP but there was a greater reduction in the aortic systolic BP (20 ± 3 vs 7 ± 2 mmHg, p  Conclusion This short-term study suggests that the effects of amlodipine on arterial stiffness are primarily on muscular rather than elastic arteries. This should be kept in mind when choosing the HTN treatment in elderly and those with diseases affecting the aorta.

Objective: Smoking and hypertension are important risk factors in the development of cardiovascular disease (CVD). Control rates of hypertension are quite poor with only <50% of patients achieving target blood pressure (BP) after antihypertensive monotherapy. Smokers may have a blunted response to antihypertensive drugs but this has not been properly investigated. Therefore we studied the interaction between smoking status and BP response in never-treated hypertensive patients. Design and method: We studied 305 untreated hypertensive subjects (mean age 51 ± 1, mean ± SEM, F = 124) classified according to their smoking status; non- smoker (n = 134), smoker (n = 64) and ex- smoker (n = 104). Haemodynamic measurements including systolic and diastolic BP and heart rate (HR) were measured before and 1 month after monotherapy with commonly used antihypertensive agents;Data were analyzed using with JMP version 7.1 (SAS) for Windows. Results were expressed as mean ± SEM, with p < 0.05 considered significant. Results: There was a significant relationship between smoking status and fall in BP; smokers and ex- smokers showed lower reduction than non- smokers for systolic BP (4 ± 1.7 vs. 13.6 ± 1 vs. 17.6 ± 1) and diastolic BP (6.5 ± 1.0 vs. 8.7 ± 0.8 vs. 10 ± 0.7, p < 0.01) respectively. In a stepwise regression analysis, baseline systolic BP, smoking status and female gender were the only significant predictors of fall in systolic BP (R2 = 0.19, p < 0.0001) with smokers exhibiting 2 mm Hg less fall than smokers and ex-smokers. For reduction in diastolic BP, baseline diastolic BP and smoking status were the only significant predictors R2 = 0.19, p < 0.0001) with smokers showing 2 mmHg less reduction in diastolic BP compared with non- smokers. Conclusions: Smoking is not only an important cardiovascular risk factor in hypertensive patients but also reduces the response to anti-hypertensive treatment, independent of age, gender and body mass index. Therefore, smoking cessation can achieve not only reduced cardiovascular risk but may also improve BP control in hypertensive patients.

Objective: Ageing is characterized by deposition of complexes of carbohydrates and proteins that form irreversible links with collagen in the vessel wall, called advanced glycation end-products (AGEs). The receptors for AGEs(RAGE) are also present in the circulating form and once activated by AGEs, they trigger inflammation, formation of reactive oxygen species and a pro-thromobotic state, resulting in stiff arteries and increased risk of cardiovascular events. We wanted to study the relationship between RAGE polymorphisms 429T > C and -374T > A and arterial stiffness in a never treated hypertensive population. Design and method: Three hundred and ten untreated hypertensive patients were recruited.and tested for genotypes of –374T > A and –429T > C. Haemodynamic measurements included brachial and aortic blood pressure, pulse wave velocity(PWV) and augmentation index(AIx).Results were analysed with JMP(SAS for Windows, p < 0.05 considered significant. Results: Both polymorphisms were in Hardy-Weinberg equilibrium. 429C allele carriers had lower PWV compared to 429TT individuals, indicating T to be the risk allele. -429CC individuals had lower PWV compared to wild type homozygotes (-429TT) plus heterozygotes (-429CT) -374T allele carriers had higher PWV compared to 374AA individuals, indicating T to be the risk allele.-374AA individuals had lower PWV compared to wild type homozygotes (-374TT) plus heterozygotes (-374AT). Similar relationship was seen after adjusting for confounders including age, mean arterial pressure, heart rate, BMI for both polymorphism. Haplotype analysis further confirmed the protective effect on PWV by these two alleles. No such relationship was observed for AIx. Conclusions: The present study shows a dose-response relationship between polymorphisms in the RAGE gene (–374 T > A and –429T > C promoter region and PWV in never-treated hypertensive patients. Furthermore, both polymorphisms were independent predictors of arterial stiffness in these patients. The T allele carriers in both the–374 T > A and –429T > C polymorphism have significantly higher arterial stiffness which is independent of other confounding factors. Finally, there is a dose-response relationship between the haplotypes of the two polymorphisms and PWV in this patient population. No significant relationship was observed between the polymorphisms and AIx.

Background Mental stress, dynamic exercise and cold pressor stimulation all increase blood pressure (BP); however, their effects on arterial stiffness are not well described. Methods : Twenty-three young healthy subjects (14 female/9 males), aged 18–30 years (23 ± 3 years), underwent mental arithmetic stress (mental arithmetic test [MAT]), cold presser test (CPT) and dynamic exercise (30% of maximal voluntary contraction [30% MVC]). Blood pressure and indices of arterial stiffness, pulse wave velocity (PWV; m/sec) and augmentation index (AIx; %) were measured at baseline, during the intervention (MAT, CPT and 30% MVC), and at 5 min and 10 min after the end of the intervention on separate days within a 3-week period. All values are given as means and standard deviations; statistical analysis was carried out using JMP software (Version 7). Results During MAT, CPT and 30% MVC there were respective increases in heart rate (HR/min) 27%, 16% and 10% ( P < 0.001); systolic BP 16%, 17% and 12% ( P < 0.01); diastolic BP 15%, 23% and 15% ( P < 0.01); AIx 13%, 29% and 30% ( P < 0.05); and PWV 14%, 12% and 16% ( P < 0.01). When the model was corrected for HR, systolic BP and diastolic BP the changes both in PWV and AIx remained significant ( P < 0.01). Conclusions MAT, CPT and 30% MVC each increase the indices of arterial stiffness independently of HR and baseline blood pressure levels.

Background: The prevalence of persistent lipid abnormalities in patients receiving statins in primary and secondary care is needed to formulate recommendations for future treatment. Studies associating cardiovascular risk factors with lipid target goal achievement are lacking. Design: A cross-sectional, observational study that assessed the prevalence of persistent dyslipidemia in patients treated with statins and analyzed predictors of lipid target achievement. Methods: Serum lipid values of 22,063 statin-treated patients were studied in the context of their cardiovascular risk factors, and the potency and composition of their lipid-lowering treatment. European Society of Cardiology recommendations were used to classify patient risk, and to define LDL-cholesterol goal and normal levels for HDL-cholesterol and triglycerides. Results: Overall, 48.2% of patients did not achieve the therapeutic goal for LDL-cholesterol, either as a single lipid anomaly or associated with low HDL-cholesterol, elevated triglycerides, or both. Lack of goal achievement was more prevalent among low-risk patients (55.8%) than high-risk patients (46.8%). Serum LDL-cholesterol levels were lower in high-risk patients. Predictors associated with LDL-cholesterol goal achievement were higher statin dose (odds ratio (OR): 0.35), specialist treatment (OR: 0.74), or combined lipid-lowering therapy (OR: 0.80). Conclusions: Nearly half of statin-treated patients missed their therapeutic LDL-cholesterol goal, highlighting a gap between recommendations and clinical practice. Better achievement of LDL-cholesterol therapeutic goal was found among patients at high cardiovascular risk, those on high statin doses or using combination therapy, and patients managed by specialists. Results suggest that residual dyslipidemia in statin-treated patients at low cardiovascular risk may be reduced by increasing statin dose.

Background Statins are proven to reduce cardiovascular risk; however, substantial risk remains in patients on statin therapy. Persisting dyslipidaemia is likely to play a contributory role. Aim To assess the prevalence of persisting lipid abnormalities in patients treated with statins. Methods DYSIS was a cross-sectional study of 22,063 patients in Europe and Canada. 900 Irish patients participated. All patients were ≥45 years and treated with statins for ≥3 months. Data were collected from the patients’ records. ESC guidelines were used to classify risk and to define lipid levels. Results Mean age was 66.1 years with women representing 40.7%. 78.6% were high-risk patients; that is 53.9% with cardiovascular disease (CVD), 20.1% with diabetes and 15.9% with a SCORE risk ≥5%. Total cholesterol was not at goal in 34.4% of all patients. LDL-C was elevated in 30.8% of all patients and in 30% at high risk. Low HDL-C was found in 34.7% of high-risk patients compared to 16.9% of patients with an ESC score <5%. In diabetics without CVD, low HDL-C and elevated TGs were found in 46 and 44.3%, respectively. Conclusions Despite statin therapy, a significant number of patients have persistent dyslipidaemia. While LDL-C targets are suboptimal in three out of ten patients, the prevalence of low HDL-C and high TGs in high-risk patients is greater than one in three. A more integrated approach to the treatment of patients with dyslipidaemia is warranted. Clinical trials are needed to assess the impact of therapies that raise HDL-C and lower elevated TGs.

Objectives:There is evidence to suggest that noncompliant and nonpersistent behaviors have differing risk factors, clinical consequences, and responses to intervention. This has led to calls for these behaviors to be defined and measured separately to characterize medication-taking behavior comprehensively. Current prescription refill models of compliance are, however, unable to appropriately distinguish between noncompliant and nonpersistent behaviors. To address this limitation, a prescription refill model of medication-taking behavior in which noncompliance and nonpersistence are treated as competing risks is presented.Methods:The proposed competing risks model of compliance and persistence is compared with a selection of widely applied prescription refill models of compliance and persistence using a common cohort of patients prescribed statin therapy.Results:The competing risks model allows the simultaneous measurement of noncompliance and nonpersistence, the partitioning of their individual contributions to medication-taking behavior, and the estimation of noncompliance risk for patients with varying treatment persistence. The results from this model provide information about the relative and overall contributions of noncompliant and nonpersistent behaviors to medication-taking behavior. The methodology also allows an assessment of the differential influence of various risk factors on these behaviors.Conclusions:The proposed competing risks model differentiates between noncompliant and nonpersistent behaviors using prescription refill data. Results from the model provide insights into the dynamics of noncompliant and nonpersistent behaviors that have not been possible with current prescription refill methodologies.

AIMS:Optimization of drug prescribing in older populations is a priority due to the significant clinical and economic costs of drug-related illness. This study aimed to: (i) estimate the prevalence of potentially inappropriate prescribing (PIP) in a national Irish older population using European specific explicit prescribing criteria; (ii) investigate the association between PIP, number of drug classes, gender and age and; (iii) establish the total cost of PIP. METHODS:This was a retrospective national population study (n= 338 801) using the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. The HSE-PCRS uses the WHO Anatomical Therapeutic Chemical (ATC) classification system and details of every drug dispensed and claimants' demographic data are available. Thirty PIP indicators (STOPP) were applied to prescription claims for those >or=70 years in Ireland in 2007. STOPP is a physiological system based screening tool of older persons' potentially inappropriate prescriptions assessing drug-drug and drug-disease interactions, dose and duration. RESULTS:In our study population PIP prevalence was 36% (121 454 claimants). The main contributors to this were: 56 560 (17%) prescribed proton pump inhibitors at maximum therapeutic dose for >8 weeks, 29 691 (9%) prescribed non-steroidal anti-inflammatories for >3 months, 17 676 (5%) prescribed long-acting benzodiazepines for >1 month and 16 201 (5%) prescribed duplicate drugs. The main determinant of PIP was polypharmacy. The likelihood of PIP increased with a significant linear and quadratic trend (P < 0.0001) with the number of drug classes.The maximum net ingredient cost of PIP was estimated to be euro38 664 640. Total PIP expenditure was estimated to be euro45 631 319, 9% of the overall expenditure on pharmaceuticals in those >or=70 years in 2007. CONCLUSIONS:The findings identify a high prevalence of PIP in Ireland with significant cost consequences.

BACKGROUND:A standard 12-lead electrocardiogram (ECG) is performed in all hypertensive patients, primarily to detect left ventricular hypertrophy. Echocardiographic assessment of hypertensive subjects reveals that abnormalities in diastolic function occur more commonly and earlier than increased left ventricular mass. However, ECG changes associated with diastolic dysfunction (DD) remain poorly defined; we assessed the ventricular activation time (VAT) (i.e., the time for the ventricle to depolarize) as a potential marker for DD in early hypertension.METHODS:Ninety subjects (aged 46 +/- 1.3 years; 43 men) with newly diagnosed, untreated hypertension underwent ECG and comprehensive two-dimensional echocardiography. Left ventricular DD was echocardiographically assessed using Canadian Consensus Guidelines. We compared VAT, which corresponds to the QR interval in the 12-lead ECG, with echocardiographic parameters of DD.RESULTS:VAT was prolonged in subjects with DD (46.3 +/- 0.4 vs. 39.6 +/- 0.3 ms, P < 0.01). There was a significant correlation between VAT and tissue Doppler imaging (TDI) (early diastolic velocity) e' (r = -0.53, P < 0.0001), (ratio of early and late diastolic velocities) e'/a' (r = -0.53, P < 0.0001), transmitral Doppler (TMD) (early peak filling rate, and early deceleration peak) E/A (r = -0.32, P = 0.001), and (ratio of early diastolic mitral inflow and early diastolic velocities) E/e' (r = 0.44, P < 0.0001).CONCLUSION:Prolongation of the VAT is associated with DD in patients with newly diagnosed untreated hypertension.

Purpose: The primary purpose was to determine the prevalence of renal artery stenosis (RAS) in patients presenting with acute ("flash") pulmonary oedema (FPE), without identifiable cause using contrast-enhanced magnetic resonance angiography (CE-MRA) of renal arteries. A secondary goal was to correlate clinical parameters at presentation with the presence or absence of RAS.Materials and methods: Patients presenting with acute pulmonary oedema without identifiable cause prospectively underwent CE-MRA. >50% renal artery stenosis was considered significant. Clinical parameters (blood pressure, serum creatinine, history of hypertension/hyperlipidaemia) were compared in patients with and without RAS using an unpaired t-test. Results expressed; mean (+/-SD).Results: 20 patients (4 male, 16 female, age 78.5+/-11 years) underwent CE-MRA. 9 patients (45%) had significant RAS (6 (30%) bilateral, 3 (15%) unilateral). Systolic BP was higher in patients with RAS (192+/-38 mm Hg) than those without (134+/-30 mm Hg) (p<.005). Diastolic BP was higher in patients with RAS (102+/-23 mm Hg) than those without (76+/-17 mm Hg) (p<.01). All patients with RAS and 6/11(55%) patients without RAS had a history of hypertension. No significant difference in creatinine or hyperlipidaemia history was observed.Conclusion: The prevalence of RAS in patients presenting with FPE is 45%. The diagnosis should be considered in patients presenting with unexplained acute pulmonary oedema, particularly if hypertensive at presentation. (C) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

BACKGROUND:Surveys evaluating plasma lipid goal attainment in patients with coronary heart disease have shown that hypercholesterolaemia is inadequately treated. Limited data account for the reasons behind this. The aim of the CEntralized Pan-European survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS) survey was to evaluate the current use and efficacy of lipid-lowering drugs (LLD), and to identify possible patient/physician characteristics associated with failure to achieve low-density lipoprotein cholesterol (LDL-C) targets recommended by the 2003 European guidelines (Third Joint Task Force). METHODS:CEPHEUS was a European, multi-centre, cross-sectional survey conducted in eight countries and involved patients on LLD for >3 months (stable medication >6 weeks). One visit was scheduled for data collection, including fasting lipids. In all but one country, physicians and patients filled in a questionnaire about aspects of hypercholesterolaemia and treatment. RESULTS:Of the 15 199 patients recruited, 14 478 were included in the final analyses. The mean age was 63.2 years, and 45% of patients were female. Overall, 55.3% of the patients achieved their LDL-C target. In multivariate analyses, the factors identified as positive predictors for achieving LDL-C goals included normal body mass index, not smoking, not having metabolic syndrome, being on statin therapy and good treatment adherence. LIMITATIONS:The population was a selected group of subjects treated with LLD, and the results cannot be extrapolated to the general population. Patient consent was obtained, which may have selected more motivated patients and induced a positive bias. The physician and patient questionnaires were not validated, but were only used for exploratory purposes. CONCLUSION:Only 55.3% of patients using LLD achieved the LDL-C target recommended in the 2003 European guidelines.

BACKGROUND:Hypertension is the commonest medical condition in Ireland.AIMS:(1) To examine the level of awareness of blood pressure (BP) in the population and (2) to ascertain the opinion of general practitioners (GPs) in diagnosis and management of hypertension.METHODS:BP measurements and assessment of BP awareness were performed in a sub-sample of the general population (n = 1,071). The opinion of GPs (n = 1,037) on hypertension was determined in a postal survey.RESULTS:Amongst the population sampled (45 ± 13 years, mean age ± SD), almost half had elevated BP (>140/90 mmHg) but only half of those were already on antihypertensives. 40% had no knowledge of their BP and 54% were not aware of what constituted normal BP. While some 80% of GPs said they followed British guidelines, their practice was more in keeping with the European guidelines. Approximately, 90% of GPs required ambulatory BP recording to confirm diagnosis of hypertension. First choice antihypertensive agents were ACE inhibitors and angiotensin receptor antagonists in younger patients and diuretics and ACE inhibitors in older patients.CONCLUSION:These results suggest that there is a need for further public education on BP and nationally agreed hypertension guidelines.