Cellular Calcium Regulation in Hypertension

In vascular muscle cells, two distinct types of functionally important calcium (Ca2++) channels, called transient (T) and sustained (L), are differentiated by dihydropyridine calcium antagonists (CaA). We studied the ratio of T/L Ca2++ channels in isolated, spontaneously contracting azygous venous cells of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) by quantitating Ca2++ currents and intracellular Ca2++ release. While total transmembranous Ca2++ current was not different between the two strains, the proportion of Ca2++ currents carried by L-type channels was enhanced in vascular muscle cells from SHR. We have recently compared subcellular distribution of intracellular free Ca2++ concentration in the same cells, at rest and during stimulation, by quantitation with a digital photon-counting camera. Fura-2 fluorescence intensity showed that Ca2++ release was principally from sarcoplasmic reticulum and that cells from SHR had higher levels of Ca2++ upon calcium channel stimulation, especially at the cell periphery. These findings suggest fundamental differences in SHR and WKY vascular muscle cells implicating the importance of changes in calcium channels, modulation of Ca2++ release, and Ca2++ uptake in SHR hypertension. Am J Hypertens 1989;2:655-65

Outcome of patients admitted with acute coronary syndrome on palliative treatment: insights from the nationwide AMIS Plus Registry 1997-2014.

OBJECTIVE: Compliance with guidelines is increasingly used to benchmark the quality of hospital care, however, very little is known on patients admitted with acute coronary syndromes (ACS) and treated palliatively. This study aimed to evaluate the baseline characteristics and outcomes of these patients. DESIGN: Prospective cohort study. SETTING: Eighty-two Swiss hospitals enrolled patients from 1997 to 2014. PARTICIPANTS: All patients with ACS enrolled in the AMIS Plus registry (n=45,091) were analysed according to three treatment groups: palliative treatment, defined as use of aspirin and analgesics only and no reperfusion; conservative treatment, defined as any treatment including antithrombotics or anticoagulants, heparins, P2Y12 inhibitors, GPIIb/IIIa but no pharmacological or mechanical reperfusion; and reperfusion treatment (thrombolysis and/or percutaneous coronary intervention during initial hospitalisation). The primary outcome measure was in-hospital mortality and the secondary measure was 1-year mortality. RESULTS: Of the patients, 1485 (3.3%) were palliatively treated, 11,119 (24.7%) were conservatively treated and 32,487 (72.0%) underwent reperfusion therapy. In 1997, 6% of all patients were treated palliatively and this continuously decreased to 2% in 2013. Baseline characteristics of palliative patients differed in comparison with conservatively treated and reperfusion patients in age, gender and comorbidities (all p<0.001). These patients had more in-hospital complications such as postadmission onset of cardiogenic shock (15.6% vs 5.2%; p<0.001), stroke (1.8% vs 0.8%; p=0.001) and a higher in-hospital mortality (25.8% vs 5.6%; p<0.001).The subgroup of patients followed 1 year after discharge (n=8316) had a higher rate of reinfarction (9.2% vs 3.4%; p=0.003) and mortality (14.0% vs 3.5%; p<0.001). CONCLUSIONS: Patients with ACS treated palliatively were older, sicker, with more heart failure at admission and very high in-hospital mortality. While refraining from more active therapy may often constitute the most humane and appropriate approach, we think it is important to also evaluate these patients and include them in registries and outcome evaluations. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT01 305 785

Angiotensin II-receptor subtypes in human atria and evidence for alterations in patients with cardiac dysfunction

Angiotensin II (All) has been implicated as an important factor in the pathophysiology of heart diseases. Following the recent identification of two subtypes of the All receptor in cardiac tissue of animals, we investigated the possible occurrence of these, or similar, subtypes in human atrial tissue. In right-atrial tissue from patients undergoing heart surgery, we determined the All-receptor profile in receptor binding studies, using [125I]-angiotensin as radioligand and All as well as two compounds selective for the receptor subtypes to identify and quantify All-receptor subpopulations. In 35 patients (23 requiring coronary bypasses, 10 vaivular surgery and two combined coronary and valvular surgery), the left-ventricular ejection fraction was determined in the preoperative phase, and right- and left-atrial pressure during surgery. In membranes of human right atria, All receptors are present in high density (median: Bmax= 294 fmol. mg−1 protein, range: 111-2073) and two different subtypes can be distinguished. Type-1 receptors (AT1) accounted for 33 ± l0% of the population whereas type-2 receptors (AT2) made up 67 ± 10% of the population. There was no correlation between any of the measured cardiac functions and total All-receptor density or receptor affinity. However, the percentage of AT1 receptors was higher in the atria of patients with normal right-atrial pressure; left-ventricular ejection fraction was positively and right-atrial pressure inversely correlated with the percentage of AT1 receptors (r=0·740 and -0·901, respectively; P<0·001, for both). Moreover, the percentage of AT receptors was directly correlated with the levels of left-atrial pressure (r=0·853; P<0·001). It is concluded that the ratio of AT1 to AT2 receptors correlates well with right-atrial pressure and left-ventricular function. This is a first indication of a possible involvement of All-receptor subtypes in the pathophysiology of cardiac dysfunction

Calcium antagonist induced vasodilation in peripheral, coronary and cerebral vasculature as important factors in the treatment of elderly hypertensives

Increased arteriolar tone is the pathophysiological hallmark of essential hypertension and is determined by the intracellular free calcium concentration in the vascular smooth muscle cell. Calcium influx is an important determinant of vasoconstriction and excess calcium influx-dependent vasoconstriction has been shown by plethysmographical studies in patients with essential hypertension. Calcium antagonists acutely lower BP by reducing calcium influx, calcium concentration and peripheral resistance. The degree of the attendant sympathetic nerve reflex activation and counter-regulatory mechanisms determines the antihypertensive response of the individual. Chronic monotherapy with a calcium antagonist results in an antihypertensive response, which is directly related to the patient's age and pretreatment BP and indirectly related to plasma renin levels. The resulting reduction in after-load neither leads to reduced cerebral blood flow in hypertensive patients, nor aggravates congestive heart failure. Calcium antagonists are a useful alternative to diuretics, primarily in older patients with low renin levels, either alone or combined with any other antihypertensive drug, and provide effective and safe control of blood pressur

Is pretreatment with Beta-blockers beneficial in patients with acute coronary syndrome?

OBJECTIVES: The role of beta-blockers in the treatment of hypertension is discussed controversially and the data showing a clear benefit in acute coronary syndromes (ACS) were obtained in the thrombolysis era. The goal of this study was to analyze the role of pretreatment with beta-blockers in patients with ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) registry, we analyzed outcomes of patients with beta-blocker pretreatment in whom they were continued during hospitalization (group A), those without beta-blocker pretreatment but with administration after admission (group B) and those who never received them (group C). Major adverse cardiac events defined as composed endpoint of re-infarction and stroke (during hospitalization) and/or in-hospital death were compared between the groups. RESULTS: A total of 24,709 patients were included in the study (6,234 in group A, 12,344 in group B, 6,131 in group C). Patients of group B were younger compared to patients of group A and C (62.5, 67.6 and 68.4, respectively). In the multivariate analysis, odds ratio for major adverse cardiac events was 0.59 (CI 0.47-0.74) for group A and 0.66 (CI 0.55-0.83) for group B, while group C was taken as a reference. CONCLUSIONS: beta-Blocker therapy is beneficial in ACS and they should be started in those who are not pretreated and continued in stable patients who had been on chronic beta-blocker therapy before

Comparative Effects of Haemodialysis and Haemofiltration on Plasma Atrial Natriuretic Peptide

The effects of 4 h haemodialysis (15 patients) or 4 h haemofiltration (five patients) on plasma concentrations of atrial natriuretic peptide (ANP) were compared by means of a sensitive radioreceptor binding assay, and related to accompanying changes in body weight, blood pressure and plasma renin activity. Before dialysis, plasma ANP concentrations were considerably elevated: haemodialysis group 10-484 pmol/l (mean 156 pmol/l); haemofiltration group 72-320 pmol/l (mean 170 pmol/l). Although plasma concentrations of ANP fell markedly with treatment in both groups: post-haemodialysis 2-187 pmol/l (mean 67 pmol/l); post-haemofiltration 47-135 pmol/l (mean 79 pmol/l), after treatment it remained above the normal range in 14 of the 20 patients. Pretreatment plasma ANP was related to systolic blood pressure (r=0.459; P<0.05) but bore no relationship to mean or diastolic blood pressure, or plasma renin activity. The fall in plasma ANP concentration during treatment correlated with the postural blood pressure drop after dialysis (r=0.505; P<0.05), but was unrelated to changes in weight or plasma renin activity with haemodialysis or haemofiltration. Plasma ANP concentrations rose rapidly again in the 60 min after dialysis treatment, without change in body weight. These results show that high levels of biologically active ANP circulate in end-stage renal disease. The fact that these are not reduced to normal by haemodialysis or haemofiltration, despite restoration to normovolaemic or hypovolaemic state, suggests that the increased levels of ANP in end-stage renal failure are due to both hypervolaemia and other factors, which may include occult cardiac dysfunction and loss of renal clearanc

Angiotensin II Receptor Subtypes and Cardiac Function

All the components of the renin-angiotensin system have been identified in the heart including the angiotensin II receptor subtypes AT1 and AT2 In the normal human heart, there is a decreasing receptor density from the right atrium to the left ventricle. In right atrial membranes prepared from pathological hearts, the percentage of AT1 receptor decreases with the severity of cardiac dysfunction whereas that of AT2 receptor increases. Treatment of hypertrophic rats with AT1 receptor antagonists inhibits cardiac hypertrophy and reverses the increase receptor density, indicating involvement of this Ang II receptor subtype. The role of the AT2 receptor is still largely unknown but it may be involved in cell growth and proliferation. The cloning of both AT1 and AT2 receptors as well as the availability of potent and selective antagonists will help us to understand better the functional role of Angiotensin II in cardiovascular disorder

Comparison of office, home and ambulatory blood pressure measurements in hypertensive and suspected hypertensive SWICOS participants.

PURPOSE Hypertension should be confirmed with the use of home BP measurement (HBPM) or 24h ambulatory BP measurement (ABPM). The aim of our study was to compare measurements obtained by OBPM, HBPM and ABPM in individuals with elevated OBPM participating in the population-based Swiss Longitudinal Cohort Study (SWICOS). MATERIAL AND METHODS Participants with OBPM ≥140/90 mmHg assessed their BP using HBPM and ABPM. The cut-off for hypertension was ≥135/85 mmHg for HBPM, ≥130/80 mmHg for ABPM. White-coat hypertension (WCH) was defined as normal HPBM and ABPM in participants not taking antihypertensive drugs. Uncontrolled hypertension was defined as hypertension in HBPM or ABPM despite antihypertensive treatment. RESULTS Of 72 hypertensive subjects with office BP ≥140/90 mmHg and valid measurements of HBPM and ABPM, 39 were males (aged 62.8 ± 11.8y), 33 were females (aged 57.4 ± 14.2y). Hypertension was confirmed with HBPM and ABPM in 17 participants (24%), with ABPM only in 24 further participants (33%), and with HBPM only in 2 further participants (3%). Participants who had hypertension according to ABPM but not HBPM were younger (59 ± 11 y versus 67 ± 16 y; p < 0.001) and more frequently still working (83% versus 23%; p < 0.001). The prevalence of WCH was 28%. Among the 32 subjects taking antihypertensive drugs, uncontrolled hypertension was found in 49%. CONCLUSION This population-based study found a high prevalence of WCH and potential uncontrolled hypertension among individuals with elevated OBPM. This study, therefore, supports the ESH recommendations of complementing OBPM by ABPM or HBPM. The use of HBPM instead of ABPM for the confirmation of hypertension in individuals with elevated OBPM might lead to underdiagnosis and uncontrolled hypertension, in particular in the younger working population. In these individuals, this study suggests using ABPM instead of HBPM

Vascular risk factors in the Swiss population

Background and Purpose : Identification of the population at risk of stroke remains the best approach to assess the burden of cardiovascular morbidity and mortality. Methods : The prevalence of hypertension (HT), hypercholesterolemia (HCh), diabetes mellitus (DM), overweight (OW), obesity (OB), tobacco use (SM), and their combinations was examined in 4458 Swiss persons (1741 men and 2717 women, mean age 57.8 ± 15 years), who volunteered for the present survey. Results : OW was the most prevalent risk factor (50 %), followed by HT (47%), HCh (33%), SM (13 %) and DM (1.6 %). The proportion of persons without risk factors (RF) was 19.9%, with 1 RF 41.5%, 2 RF 33.8%, 3 RF 4%, and 4 RF 0.9%. OW was more prevalent in men than in women (53% vs. 41%, P=0.02). More men than women aged 41-50 years and 51-60 years had HT (49 % vs. 36%, P=0.01, and 52 % vs. 42%, P=0.02). The prevalence of HCh and DM did not show any sex-related differences. HT, OW and HCh were not only the most common single risk factors, but were also most likely to aggregate with each other. Conclusions : The majority of Swiss people have one or two vascular risk factors. OW and HT are by far most common and are likely to aggregate with each other. A small modification of these two factors would reduce the incidence of stroke and myocardial infarction significantl