Phenotypes of masked hypertension: isolated ambulatory, isolated home and dual masked hypertension

Objectives: Masked hypertension (MH) is defined as normal office blood pressure (OBP) and elevated ambulatory (ABP) or home blood pressure (HBP). This study assessed MH identified by each of these two methods. Methods: A retrospective analysis of cross-sectional data in treated and untreated adults from Greece, Finland and UK who had OBP, HBP and 24-h ABP measurements was performed. Dual MH was defined as normal OBP and elevated HBP and ABP, isolated ambulatory MH as normal OBP and HBP and elevated ABP and isolated home MH as normal OBP and ABP and elevated HBP. Results: Of 1971 participants analyzed, 445 (23%) had MH on ABP and/or HBP (age 57.1 ± 10.8 years, men 55%, treated 49%). Among participants with any MH, 215 had dual MH (48%), 132 isolated ambulatory MH (30%) and 98 isolated home MH (22%). Moreover, 55% had high-normal, 35% normal and 10% optimal OBP. In logistic regression analysis isolated ambulatory MH was predicted by younger age (OR 0.35, P < 0.01 per 10 years increase), whereas isolated home MH was predicted by older age (OR 2.05, P < 0.01 per 10 years increase). Conclusion: Masked hypertension diagnosed by ABP and not HBP monitoring or the reverse is not uncommon. Age appears to be the most important determinant of isolated ambulatory or home MH, with the former being more common in younger participants and the latter in older ones. Only half of participants with MH have high-normal OBP, whereas the rest have lower levels

Ambulatory versus home blood pressure monitoring: frequency and determinants of blood pressure difference and diagnostic disagreement

Objectives: Out-of-office blood pressure evaluation assessed using ambulatory (ABP) or home (HBP) monitoring is currently recommended for hypertension management. We evaluated the frequency and determinants of diagnostic disagreement between ABP and HBP measurements. Methods: Cross-sectional data from 1971 participants (mean age 53.8 +/- 11.4 years, 52.6% men, 32% treated) from Greece, Finland and the United Kingdom were analyzed. The diagnostic disagreement between HBP and daytime ABP was regarded as certain when (i) the two methods diagnosed a different blood pressure phenotype, (ii) the absolute HBP-ABP difference was more than 10/5 mmHg (systolic/diastolic) and (iii) ABP and HBP had a more than 5 mmHg difference from the respective hypertension threshold. Results: In 1574 participants (79.9%), there was agreement between HBP and ABP in diagnosing hypertensive phenotypes (kappa 0.70). Of the remaining 397 participants (20.1%) with diagnostic disagreement, 95 had clinically irrelevant HBP-ABP differences, which reduced the disagreement to 15.3%. When cases with ABP and/or HBP differing <= 5 mmHg from the respective hypertension threshold were excluded, the certain disagreement between the two methods was reduced to 8.2%. Significant determinants of the HBP-ABP difference were age, sex, study center, BMI, cardiovascular disease history, office hypertension and antihypertensive treatment. Antihypertensive drug treatment, alcohol consumption and office normotension independently increased the odds of diagnostic disagreement. Conclusion: These data suggest that there is considerable diagnostic agreement between HBP and ABP, and that these methods are interchangeable for clinical decisions in most patients. However, considerable disagreement between the two methods occurs in an appreciable minority, most likely due to methodological and patient-related factors

The Metabolic Syndrome and the immediate antihypertensive effects of aerobic exercise: a randomized control design

<p>Abstract</p> <p>Background</p> <p>The metabolic syndrome (Msyn) affects about 40% of those with hypertension. The Msyn and hypertension have a common pathophysiology. Exercise is recommended for their treatment, prevention and control. The influence of the Msyn on the antihypertensive effects of aerobic exercise is not known. We examined the influence of the Msyn on the blood pressure (BP) response following low (LIGHT, 40% peak oxygen consumption, VO₂peak) and moderate (MODERATE, 60% VO₂peak) intensity, aerobic exercise.</p> <p>Methods</p> <p>Subjects were 46 men (44.3 ± 1.3 yr) with pre- to Stage 1 hypertension (145.5 ± 1.6/86.3 ± 1.2 mmHg) and borderline dyslipidemia. Men with Msyn (n = 18) had higher fasting insulin, triglycerides and homeostasis model assessment (HOMA) and lower high density lipoprotein than men without Msyn (n = 28) (p < 0.01). Subjects consumed a standard meal and 2 hr later completed one of three randomized experiments separated by 48 hr. The experiments were a non-exercise control session of seated rest and two cycle bouts (LIGHT and MODERATE). BP, insulin and glucose were measured before, during and after the 40 min experiments. Subjects left the laboratory wearing an ambulatory BP monitor for the remainder of the day. Repeated measure ANCOVA tested if BP, insulin and glucose differed over time among experiments in men without and with the Msyn with HOMA as a covariate. Multivariable regression analyses examined associations among BP, insulin, glucose and the Msyn.</p> <p>Results</p> <p>Systolic BP (SBP) was reduced 8 mmHg (p < 0.05) and diastolic BP (DBP) 5 mmHg (p = 0.052) after LIGHT compared to non-exercise control over 9 hr among men without versus with Msyn. BP was not different after MODERATE versus non-exercise control between Msyn groups (p ≥ 0.05). The factors accounting for 17% of the SBP response after LIGHT were baseline SBP (β = -0.351, r²= 0.123, p = 0.020), Msyn (β = 0.277, r²= 0.077, p = 0.069), and HOMA (β = -0.124, r²= 0.015, p = 0.424). Msyn (r²= 0.096, p = 0.036) was the only significant correlate of the DBP response after LIGHT.</p> <p>Conclusion</p> <p>Men without the Msyn respond more favorably to the antihypertensive effects of lower intensity, aerobic exercise than men with the Msyn. If future work confirms our findings, important new knowledge will be gained for the personalization of exercise prescriptions among those with hypertension and the Msyn.</p

Epidemiological and economic burden of metabolic syndrome and its consequences in patients with hypertension in Germany, Spain and Italy; a prevalence-based model

<p>Abstract</p> <p>Background</p> <p>The presence of metabolic syndrome in patients with hypertension significantly increases the risk of cardiovascular disease, type 2 diabetes and mortality. Our aim is to estimate the epidemiological and economic burden to the health service of metabolic syndrome in patients with hypertension in three European countries in 2008 and 2020.</p> <p>Methods</p> <p>An age, sex and risk group structured prevalence based cost of illness model was developed using the United States Adult Treatment Panel III of the National Cholesterol Education Program criteria to define metabolic syndrome. Data sources included published information and public use databases on disease prevalence, incidence of cardiovascular events, prevalence of type 2 diabetes, treatment patterns and cost of management in Germany, Spain and Italy.</p> <p>Results</p> <p>The prevalence of hypertension with metabolic syndrome in the general population of Germany, Spain and Italy was 36%, 11% and 10% respectively. In subjects with hypertension 61%, 22% and 21% also had metabolic syndrome. Incident cardiovascular events and attributable mortality were around two fold higher in subjects with metabolic syndrome and prevalence of type 2 diabetes was around six-fold higher. The economic burden to the health service of metabolic syndrome in patients with hypertension was been estimated at €24,427, €1,900 and €4,877 million in Germany, Spain and Italy and forecast to rise by 59%, 179% and 157% respectively by 2020. The largest components of costs included the management of prevalent type 2 diabetes and incident cardiovascular events. Mean annual costs per hypertensive patient were around three-fold higher in subjects with metabolic syndrome compared to those without and rose incrementally with the additional number of metabolic syndrome components present.</p> <p>Conclusion</p> <p>The presence of metabolic syndrome in patients with hypertension significantly inflates economic burden and costs are likely to increase in the future due to an aging population and an increase in the prevalence of components of metabolic syndrome.</p

Soluble CD4 and CD4-Mimetic Compounds Inhibit HIV-1 Infection by Induction of a Short-Lived Activated State

Binding to the CD4 receptor induces conformational changes in the human immunodeficiency virus (HIV-1) gp120 exterior envelope glycoprotein. These changes allow gp120 to bind the coreceptor, either CCR5 or CXCR4, and prime the gp41 transmembrane envelope glycoprotein to mediate virus–cell membrane fusion and virus entry. Soluble forms of CD4 (sCD4) and small-molecule CD4 mimics (here exemplified by JRC-II-191) also induce these conformational changes in the HIV-1 envelope glycoproteins, but typically inhibit HIV-1 entry into CD4-expressing cells. To investigate the mechanism of inhibition, we monitored at high temporal resolution inhibitor-induced changes in the conformation and functional competence of the HIV-1 envelope glycoproteins that immediately follow engagement of the soluble CD4 mimics. Both sCD4 and JRC-II-191 efficiently activated the envelope glycoproteins to mediate infection of cells lacking CD4, in a manner dependent on coreceptor affinity and density. This activated state, however, was transient and was followed by spontaneous and apparently irreversible changes of conformation and by loss of functional competence. The longevity of the activated intermediate depended on temperature and the particular HIV-1 strain, but was indistinguishable for sCD4 and JRC-II-191; by contrast, the activated intermediate induced by cell-surface CD4 was relatively long-lived. The inactivating effects of these activation-based inhibitors predominantly affected cell-free virus, whereas virus that was prebound to the target cell surface was mainly activated, infecting the cells even at high concentrations of the CD4 analogue. These results demonstrate the ability of soluble CD4 mimics to inactivate HIV-1 by prematurely triggering active but transient intermediate states of the envelope glycoproteins. This novel strategy for inhibition may be generally applicable to high–potential-energy viral entry machines that are normally activated by receptor binding

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Ambulatory versus home blood pressure monitoring: Frequency and determinants of blood pressure difference and diagnostic disagreement

OBJECTIVES:Out-of-office blood pressure evaluation assessed using ambulatory (ABP) or home (HBP) monitoring is currently recommended for hypertension management. We evaluated the frequency and determinants of diagnostic disagreement between ABP and HBP measurements. METHODS:Cross-sectional data from 1971 participants (mean age 53.8 ± 11.4 years, 52.6% men, 32% treated) from Greece, Finland and the United Kingdom were analyzed. The diagnostic disagreement between HBP and daytime ABP was regarded as certain when (i) the two methods diagnosed a different blood pressure phenotype, (ii) the absolute HBP-ABP difference was more than 10/5 mmHg (systolic/diastolic) and (iii) ABP and HBP had a more than 5 mmHg difference from the respective hypertension threshold. RESULTS:In 1574 participants (79.9%), there was agreement between HBP and ABP in diagnosing hypertensive phenotypes (kappa 0.70). Of the remaining 397 participants (20.1%) with diagnostic disagreement, 95 had clinically irrelevant HBP-ABP differences, which reduced the disagreement to 15.3%. When cases with ABP and/or HBP differing ≤5 mmHg from the respective hypertension threshold were excluded, the certain disagreement between the two methods was reduced to 8.2%. Significant determinants of the HBP-ABP difference were age, sex, study center, BMI, cardiovascular disease history, office hypertension and antihypertensive treatment. Antihypertensive drug treatment, alcohol consumption and office normotension independently increased the odds of diagnostic disagreement. CONCLUSION:These data suggest that there is considerable diagnostic agreement between HBP and ABP, and that these methods are interchangeable for clinical decisions in most patients. However, considerable disagreement between the two methods occurs in an appreciable minority, most likely due to methodological and patient-related factors