Perspectives on improving blood pressure control to reduce the clinical and economic burden of hypertension.

The clinical and economic burden of hypertension is high and continues to increase globally. Uncontrolled hypertension has severe but avoidable long-term consequences, including cardiovascular diseases, which are among the most burdensome and most preventable conditions in Europe. Yet, despite clear guidelines on screening, diagnosis and management of hypertension, a large proportion of patients remain undiagnosed or undertreated. Low adherence and persistence are common, exacerbating the issue of poor blood pressure (BP) control. Although current guidelines provide clear direction, implementation is hampered by barriers at the patient-, physician- and healthcare system levels. Underestimation of the impact of uncontrolled hypertension and limited health literacy lead to low adherence and persistence among patients, treatment inertia among physicians and a lack of decisive healthcare system action. Many options to improve BP control are available or under investigation. Patients would benefit from targeted health education, improved BP measurement, individualized treatment or simplified treatment regimens through single-pill combinations. For physicians, increasing awareness of the burden of hypertension, as well as offering training on monitoring and optimal management and provision of the necessary time to collaboratively engage with patients would be useful. Healthcare systems should establish nationwide strategies for hypertension screening and management. Furthermore, there is an unmet need to implement more comprehensive BP measurements to optimize management. In conclusion, an integrative, patient-focused, multimodal multidisciplinary approach to the management of hypertension by clinicians, payers and policymakers, involving patients, is required to achieve long-term improvements in population health and cost-efficiency for healthcare systems.

Self-rated health scores predict mortality among people with type 2 diabetes differently across three different country groupings: findings from the ADVANCE and ADVANCE-ON trials.

AIMS: To explore whether there is a different strength of association between self-rated health and all-cause mortality in people with type 2 diabetes across three country groupings: nine countries grouped together as 'established market economies'; Asia; and Eastern Europe. METHODS: The ADVANCE trial and its post-trial follow-up were used in this study, which included 11 140 people with type 2 diabetes from 20 countries, with a median follow-up of 9.9 years. Self-rated health was reported on a 0-100 visual analogue scale. Cox proportional hazard models were fitted to estimate the relationship between the visual analogue scale score and all-cause mortality, controlling for a range of demographic and clinical risk factors. Interaction terms were used to assess whether the association between the visual analogue scale score and mortality varied across country groupings. RESULTS: The visual analogue scale score had different strengths of association with mortality in the three country groupings. A 10-point increase in visual analogue scale score was associated with a 15% (95% CI 12-18) lower mortality hazard in the established market economies, a 25% (95% CI 21-28) lower hazard in Asia, and an 8% (95% CI 3-13) lower hazard in Eastern Europe. CONCLUSIONS: Self-rated health appears to predict 10-year all-cause mortality for people with type 2 diabetes worldwide, but this relationship varies across groups of countries.

Resting heart rate is associated with renal disease outcomes in patients with vascular disease: results of the ONTARGET and TRANSCEND studies.

BACKGROUND: Resting heart rate (RHR) is associated with cardiovascular disease outcomes in high-risk patients. It is not known whether RHR is predictive of renal outcomes such as albuminuria, end-stage renal disease (ESRD) or doubling of creatinine. We evaluated whether RHR could predict renal endpoints in patients at a high risk of cardiovascular disease. We also tested the effects of RHR at different levels of systolic blood pressure (SBP). METHODS: We analysed data from 28 757 patients in the ONTARGET and TRANSCEND trials. RHR and SBP were available for a mean of 4.9 ± 0.4 visits (range 3-5) within the first 2 years of the studies. Albuminuria was determined at baseline, at 2 years and at study end. RESULTS: Mean RHR was predictive of incident micro-albuminuria [hazard ratio (HR) for RHR ≥80 vs. <60 beats min(-1) 1.49, 95% confidence interval (CI) 1.29-1.71, P < 0.0001], incident macro-albuminuria (HR 1.84, 95% CI 1.39-2.42, P < 0.0001), doubling of creatinine (HR 1.47, 95% CI 1.00-2.17, P = 0.050) and ESRD (HR 1.78, 95% CI 1.00-3.16, P = 0.050), and the combined renal end-point (HR 1.51, 95% CI 1.32-1.74, P < 0.0001). Associations were robust at SBPs from <120 to ≥150 mmHg, with the lowest risk at a SBP of 130-140 mmHg. CONCLUSION: Resting heart rate is a potent predictor of these renal outcomes, as well as their combination, in patients with cardiovascular disease. RHR at all SBP levels should be considered as a possible renal disease risk predictor and should be investigated as a treatment target with RHR-reducing agents.

Intensification of medication and glycaemic control among patients with type 2 diabetes - the ADVANCE trial.

AIMS: The aim of this study was to assess associations between patient characteristics, intensification of blood glucose-lowering treatment through oral glucose-lowering therapy and/or insulin and effective glycaemic control in type 2 diabetes. METHODS: 11 140 patients from the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial who were randomized to intensive glucose control or standard glucose control and followed up for a median of 5 years were categorized into two groups: effective glycaemic control [haemoglobin A1c (HbA1c) ≤ 7.0% or a proportionate reduction in HbA1c over 10%] or ineffective glycaemic control (HbA1c > 7.0% and a proportionate reduction in HbA1c less than or equal to 10%). Therapeutic intensification was defined as addition of an oral glucose-lowering agent or commencement of insulin. Pooled logistic regression models examined the associations between patient factors, intensification and effective glycaemic control. RESULTS: A total of 7768 patients (69.7%), including 3198 in the standard treatment group achieved effective glycaemic control. Compared to patients with ineffective control, patients with effective glycaemic control had shorter duration of diabetes and lower HbA1c at baseline and at the time of treatment intensification. Treatment intensification with addition of an oral agent or commencement of insulin was associated with a 107% [odds ratio, OR: 2.07 (95% confidence interval, CI: 1.95-2.20)] and 152% [OR: 2.52 (95% CI: 2.30-2.77)] greater chance of achieving effective glycaemic control, respectively. These associations were robust after adjustment for several baseline characteristics and not modified by the number of oral medications taken at the time of treatment intensification. CONCLUSIONS: Effective glycaemic control was associated with treatment intensification at lower HbA1c levels at all stages of the disease course and in both arms of the ADVANCE trial.

Improving long-term prediction of first cardiovascular event: the contribution of family history of coronary heart disease and social status.

OBJECTIVE: The aim of this study is to assess whether family history of coronary heart disease (CHD) and education as proxy of social status improve long-term cardiovascular disease risk prediction in a low-incidence European population. METHODS: The 20-year risk of first coronary or ischemic stroke events was estimated using sex-specific Cox models in 3956 participants of three population-based surveys in northern Italy, aged 35-69 years and free of cardiovascular disease at enrollment. The additional contribution of education and positive family history of CHD was defined as change in discrimination and Net Reclassification Improvement (NRI) over the model including 7 traditional risk factors. RESULTS: Kaplan-Meier 20-year risk was 16.8% in men (254 events) and 6.4% in women (102 events). Low education (hazard ratio=1.35, 95%CI 0.98-1.85) and family history of CHD (1.55; 1.19-2.03) were associated with the endpoint in men, but not in women. In men, the addition of education and family history significantly improved discrimination by 1%; NRI was 6% (95%CI: 0.2%-15.2%), raising to 20% (0.5%-44%) in those at intermediate risk. NRI in women at intermediate risk was 7%. CONCLUSION: In low-incidence populations, family history of CHD and education, easily assessed in clinical practice, should be included in long-term cardiovascular disease risk scores, at least in men.

The diagnostic approach and management of hypertension in the emergency department.

Hypertension urgency and emergency represents a challenging condition in which clinicians should determine the assessment and/or treatment of these patients. Whether the elevation of blood pressure (BP) levels is temporary, in need of treatment, or reflects a chronic hypertensive state is not always easy to unravel. Unfortunately, current guidelines provide few recommendations concerning the diagnostic approach and treatment of emergency department patients presenting with severe hypertension. Target organ damage determines: the timeframe in which BP should be lowered, target BP levels as well as the drug of choice to use. It's important to distinguish hypertensive emergency from hypertensive urgency, usually a benign condition that requires more likely an outpatient visit and treatment.

Impact of body mass index and waist circumference on the cardiovascular risk and all-cause death in a general population: data from the PAMELA study.

BACKGROUND AND AIMS: Elevated values of body mass index (BMI) and waist circumference (WC) are associated with an augmented cardiovascular (CV) risk. It is debated, however, whether and to what extent this depends on the body fat increase 'per se' or on the related cardiometabolic alterations. METHODS AND RESULTS: In 2005 subjects randomly selected from the general population of Monza (Italy), we assessed BMI, WC, office, home and 24 h blood pressure (BP), heart rate and metabolic variables. The impact of BMI and WC on the incidence of CV events, CV and all-cause mortality was estimated during a 148-month follow-up. Progressively higher values of BMI and WC were associated with a progressive increase in office, home and 24 h BP and in erratic BP variability (P < 0.0001 for trend). Metabolic variables were directly and significantly (P < 0.0001) related to BMI and WC, while an inverse significant relationship was detected with high-density lipoprotein (HDL)-cholesterol. The incidence of CV events, CV and all-cause deaths increased progressively from the lowest to the highest quintile of BMI and WC (P for trend always <0.005). Baseline BMI and WC higher by respectively 1 kg m⁻² and 1 cm were associated with an increased risk of CV events, CV and all-cause death by 8%, 12% and 7% (for baseline BMI) and 4%, 5% and 4% (for baseline WC), respectively. After adjustment for confounders, only the increased risk of CV death related to higher baseline BMI remained significant (hazard ratio (HR) 1.062, confidence interval (CI) 95% 1.003-1.126, P < 0.05). CONCLUSION: The adverse prognostic impact of the accumulation of body fat is mediated by the associated haemodynamic and metabolic alterations. Baseline values of BMI, however, are an independent predictor of CV mortality.

Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: An association between resting heart rate and mortality has been described in the general population and in patients with cardiovascular disease. There are, however, few data exploring this relationship in patients with type 2 diabetes mellitus. The current study addresses this issue. METHODS: The relationship between baseline resting heart rate and all-cause mortality, cardiovascular death and major cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) was examined in 11,140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study. RESULTS: A higher resting heart rate was associated with a significantly increased risk of all-cause mortality (fully adjusted HR 1.15 per 10 bpm [95% CI 1.08, 1.21], p<0.001), cardiovascular death and major cardiovascular outcomes without adjustment and after adjusting for age and sex and multiple covariates. The increased risk associated with a higher baseline resting heart rate was most obvious in patients with previous macrovascular complications (fully adjusted HR for death 1.79 for upper [mean 91 bpm] vs lowest [mean 58 bpm] fifth of resting heart rate in this subgroup [95% CI 1.28, 2.50], p = .001). CONCLUSIONS/INTERPRETATION: Among patients with type 2 diabetes, a higher resting heart rate is associated with an increased risk of death and cardiovascular complications. It remains unclear whether a higher heart rate directly mediates the increased risk or is a marker for other factors that determine a poor outcome.

Decreased adrenergic tone in acromegaly: evidence from direct recording of muscle sympathetic nerve activity.

OBJECTIVE: Sympathovagal imbalance has been shown in acromegaly by indirect measurements of adrenergic tone. Data regarding direct measurement of sympathetic activity are lacking as yet. Aim of this study was to assess the adrenergic tone through direct recording of muscle sympathetic nerve activity (MSNA) in acromegalic patients. DESIGN: Fifteen patients (age 26-66 years, eight women) with newly diagnosed active acromegaly without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy, and 15 healthy subjects matched for age, sex and body mass index were recruited. After evaluating anthropometric and echocardiographic parameters, anterior pituitary function, glucose and lipid metabolism, and measuring plasma leptin, direct recording of sympathetic outflow via the microneurographic technique was performed. RESULTS: For similar anthropometric and metabolic parameters in patients and controls, HOMA index was significantly increased in the former (4·2 ± 2·39 vs 1·6 ± 0·19, P < 0·001). Surprisingly, this finding of insulin resistance was accompanied by a marked sympathetic inhibition (MSNA 18·3 ± 8·10 vs 37·3 ± 6·48 bursts/min, P < 0·0001, respectively in patients and controls). A reduction in plasma leptin (1·6 ± 1·04 vs 6·5 ± 2·01 µg/l, P < 0·0001) was also recorded in the patients. MSNA was positively correlated with leptin (P < 0·0001). CONCLUSIONS: Newly diagnosed acromegalic patients without cardiac hypertrophy display a decreased sympathetic outflow in spite of insulin resistance. This finding might be related to hypoleptinaemia.

Clinic blood pressure, ambulatory blood pressure and cardiac structural alterations in nonagenarians and in centenarians.

scant information is available on the alterations in cardiac structure and function characterizing very elderly people as well as on their relationships to clinic and ambulatory blood pressure (BP) values. In 106 subjects aged 95.3 ± 3.7 years (mean ± standard deviation, 89 nonagenarians and 17 centenarians) in good clinical conditions and living in the municipal house in Milan, we measured, along with standard clinical and laboratory variables, clinic BP, 24-h ambulatory BP and echocardiographic parameters. Forty-five of the recruited subjects were normotensive individuals, whereas 61 were treated hypertensive patients. Subjects with an age greater than 90 years showed clinic systolic (SBP) and diastolic BP (DBP) both within the normal range, with values that for clinic SBP were slightly lower than the corresponding 24-h SBP (120.8 ± 15.9 vs 128.0 ± 16.3 mmHg) and for DBP slightly higher (69.7 ± 8.8 vs 64.9 ± 8.0 mmHg). Daytime average mean BP was slightly lower than night-time average mean BP, indicating the attenuation of the BP reduction during night-time. Left ventricular mass index (LVMI) was increased and significantly related to both 24-h and clinic BP values (r = 0.24, p < 0.04 and r = 0.20, p < 0.05). Thus in nonagenarians and centenarians, abnormalities in left ventricular pattern are of frequent detection and may be related both to the ageing process and to BP load.

Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

AIMS/HYPOTHESIS: The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial. METHODS: Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 ('normal', n = 8,689), 24-27 ('mild dysfunction', n = 2,231) and <24 ('severe dysfunction', n = 212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis. RESULTS: Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11-1.46 and 1.42, 95% CI 1.01-1.99; both p < 0.05), cardiovascular death (1.41, 95% CI 1.16-1.71 and 1.56, 95% CI 0.99-2.46; both p

Metabolic syndrome and biventricular hypertrophy in essential hypertension.

The metabolic syndrome (MS) is associated with structural and functional alterations of the left ventricle (LV); no evidence is available on the impact of the MS on the right ventricle (RV). To assess whether MS, as defined by the ATP III report, is associated with biventricular hypertrophy, a total of 286 hypertensive subjects (mean age 58.7+/-12.2 years) attending our outpatient clinic underwent the following procedures: (1) physical examination and standard clinic blood pressure (BP) measurement; (2) routine laboratory investigations; (3) M-mode, two-dimensional and Doppler echocardiography. LV hypertrophy (LVH) was defined by LM mass index>or=51/47 g m(-2.7) in men and women, respectively. Right-sided chambers were measured in parasternal long axis at the outflow tract and subcostal view; RV hypertrophy (RVH) was defined by anterior RV wall thickness>or=6.0/5.5 mm in men and women, respectively. Filling velocities of both ventricles were assessed by pulsed Doppler echocardiography. Structural cardiac alterations were more pronounced in hypertensive men and women with MS than in their non-MS counterparts and involved both ventricles as shown by the differences in continuous variables as well as in prevalence rates of LVH (58 and 48% vs 28 and 30%, respectively, P<0.01) and RVH (48 and 54% vs 25 and 35%, respectively, P<0.01). Both LV and RV filling in MS hypertensives were more dependent on the atrial systole. Our study shows that in human hypertension, structural and functional cardiac changes induced by MS are not limited to the LV but also involve the right one.

Reproducibility patterns of plasma norepinephrine and muscle sympathetic nerve traffic in human obesity.

BACKGROUND AND AIMS: The present study was designed to assess the reproducibility of the two markers of adrenergic drive, venous plasma norepinephrine and efferent postganglionic muscle sympathetic nerve traffic (MSNA) in reflecting the sympathetic activation characterizing the obese state in human beings. METHODS AND RESULTS: In 15 male obese normotensive subjects (age: 40.1+/-2.2, mean+/-SEM) we measured, in two experimental sessions three weeks apart, blood pressure (BP, Finapres), heart rate (EKG), plasma norepinephrine (HPLC assay) and MSNA (microneurography, peroneal nerve). In each session three norepinephrine samples were obtained and norepinephrine reproducibility between sessions was assessed by considering a single norepinephrine sample or by averaging 2-3 samples. Reproducibility data were compared to the ones displayed by the MSNA technique. While MSNA values showed a highly significant correlation between sessions (r=0.89, p<0.001), norepinephrine values based on a single blood sample evaluation did not correlate with each other (r=0.44, p=NS). Norepinephrine correlation coefficient values increased and achieved statistical significance when average data from 3 blood samples were examined (r=0.56, p<0.03). CONCLUSIONS: In human obesity MSNA displays a reproducibility pattern higher than plasma norepinephrine. The reproducibility of the norepinephrine approach can be improved by increasing the number of blood samples on which norepinephrine assay is performed. To obtain such a goal, and to make reproducibility closer to the MSNA one, three norepinephrine samples are needed.

Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial.

BACKGROUND: Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the effects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs. METHODS: The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925. FINDINGS: After a mean of 4.3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00, p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant (macrovascular 0.92; 0.81-1.04, p=0.16; microvascular 0.91; 0.80-1.04, p=0.16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3.8%] active vs 257 [4.6%] placebo; 0.82, 0.68-0.98, p=0.03) and death from any cause was reduced by 14% (408 [7.3%] active vs 471 [8.5%] placebo; 0.86, 0.75-0.98, p=0.03). There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline. INTERPRETATION: Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confidence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy.

Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight.

This study explored the process of arterial baroreflex adaptation to microgravity, starting from the first day of flight, during the 16-day STS-107 Columbia Space Shuttle mission. Continuous blood pressure (BP), ECG, and respiratory frequency were collected in four astronauts on ground (baseline) and during flight at days 0-1, 6-7, and 12-13, both at rest and during moderate exercise (75 W) on a cycle ergometer. Sensitivity of the baroreflex heart rate control (BRS) was assessed by sequence and spectral alpha methods. Baroreflex effectiveness index (BEI); low-frequency (LF) power and high-frequency (HF) power of systolic BP (SBP), diastolic BP (DBP), and R-R interval (RRI); the RRI LF/HF ratio; and the RRI root mean square of successive differences (RMSSD) index were also estimated. We found that, at rest, BRS increased in early flight phase, compared with baseline (means +/- SE: 18.3 +/- 3.4 vs. 10.4 +/- 1.2 ms/mmHg; P < 0.05), and it tended to return to baseline in subsequent days. During exercise, BRS was lower than at rest, without differences between preflight and in-flight values. At rest, in the early flight phase, RMSSD and RRI HF power increased (P < 0.05) compared with baseline, whereas LF powers of SBP and DBP decreased. No statistical difference was found in these parameters during exercise before vs. during flight. These findings demonstrate that heart rate baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart.

Prevalence and correlates of multiple organ damage in referred treated hypertensives: data from the ETODH study.

This study, carried out in a large cohort of treated essential hypertensives attending an out-patient hospital hypertension clinic, extends previous observations by showing that a clustering of two or three markers of organ damage (OD) has a higher prevalence than a single organ involvement. These findings call for a systematic evaluation of cardiac and extracardiac OD in treated hypertensive patients referred to a specialist setting.

Ambulatory heart rate and target organ damage in never-treated essential hypertensives.

Limited evidence is available about the relationship between ambulatory heart rate (HR) and target organ damage (TOD) in uncomplicated hypertension. We sought to investigate the association between ambulatory HR and subclinical cardiac, vascular and renal markers of TOD in never-treated essential hypertensives. A total of 580 subjects with recently diagnosed (

Achieving blood pressure goals globally: five core actions for health-care professionals. A worldwide call to action.

The prevalence of hypertension continues to rise across the world, and most patients who receive medical intervention are not adequately treated to goal. A Working Group including representatives of nine international health-care organizations was convened to review the barriers to more effective blood pressure control and propose actions to address them. The group concluded that tackling the global challenge of hypertension will require partnerships among multiple constituencies, including patients, health-care professionals, industry, media, health-care educators, health planners and governments. Additionally, health-care professionals will need to act locally with renewed impetus to improve blood pressure goal rates. The Working Group identified five core actions, which should be rigorously implemented by practitioners and targeted by health systems throughout the world: (1) detect and prevent high blood pressure; (2) assess total cardiovascular risk; (3) form an active partnership with the patient; (4) treat hypertension to goal and (5) create a supportive environment. These actions should be pursued with vigour in accordance with current clinical guidelines, with the details of implementation adapted to the economic and cultural setting.

Ambulatory blood pressure, target organ damage and aortic root size in never-treated essential hypertensive patients.

The relationship between ambulatory blood pressure (ABP), target organ damage (TOD) and aortic root (AR) size in human hypertension has not been fully explored to date. We investigated the relationship between ABP, different markers of TOD and AR size in never-treated essential hypertensive patients. A total of 519 grade 1 and 2 hypertensive patients (mean age 46+/-12 years) referred for the first time to our outpatient clinic underwent the following procedures: (1) routine examination, (2) 24 h urine collection for microalbuminuria (MA), (3) ambulatory blood pressure monitoring over two 24 h periods within 4 weeks, (4) echocardiography and (5) carotid ultrasonography. AR dilatation was defined by sex-specific criteria (> or =40 mm in men and > or =37 mm in women). AR diameter was increased in 3.7% of patients. Demographic variables (body mass index, age and male gender), average night-time diastolic blood pressure (BP) (but not clinic or average 48 h BP), left ventricular mass index and carotid intima-media (IM) thickness showed an independent association with AR size in both univariate and multivariate analyses. When TOD data were analysed in a categorical way, a stepwise increase in the prevalence of left ventricular hypertrophy (LVH) (I=17.5%, II=27.6%, III=35.8%) and carotid IM thickening (I=20.9%, II=28.8%, III=34.4%), but not in MA (I=6.8%, II=9.1%, III=8.7%) was found with the progression of AR size tertiles. Our results show that (1) AR enlargement in uncomplicated never-treated hypertensive patients has a markedly lower prevalence than traditional markers of cardiac and extracardiac TOD; (2) night-time BP, LVH and carotid IM thickening are independent predictors of AR dimension.

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.