Search

The Systolic Blood Pressure Intervention Trial (SPRINT) began in the autumn of 2009 and enrolled more than 9300 participants aged 50 and older in about 100 medical centres and clinical practices th...

Impact of SBP vs. DBP decrement during orthostasis on cardiovascular events in hypertension is not clear.We assessed prospective association of orthostatic hypotension with mortality and major cardiovascular events [myocardial infarction (MI) and stroke] among 8788 treated hypertensive patients (52.2% men; mean age 52 years, mean BP 161/99 mmHg) without history of MI or stroke at baseline. Orthostatic hypotension was defined according to combined international consensus criteria, and as either systolic (decrease ≥20 mmHg) or diastolic orthostatic hypotension (decrease ≥10 mmHg). Final Cox regression model was adjusted for age, sex, supine SBP and DBP, diabetes, smoking, and total cholesterol.A total of 1060 (12.1%) study participants fulfilled combined orthostatic hypotension criteria, of these 886 (10.1%) met systolic and 290 (3.3%) diastolic criterion. In the crude analysis, combined orthostatic hypotension criteria were predictive of the composite endpoint, major cardiovascular event, total mortality, and stroke but not MI. After full adjustment, combined orthostatic hypotension criteria and systolic orthostatic hypotension were independently associated with stroke only (hazard ratio: 1.48, 1.07-2.05, P = 0.019, and 1.53, 1.08-2.15, P = 0.015, respectively), whereas the composite endpoint tended in the same direction (hazard ratio: 1.21, 0.98-1.51, P = 0.075, and 1.24, 0.99-1.55, P = 0.066, respectively). In contrast, diastolic orthostatic hypotension was associated with increased risk of MI (hazard ratio: 2.04, 1.20-3.46, P = 0.008).Orthostatic hypotension has a dual role in cardiovascular events among hypertensive patients: SBP fall indicates higher risk of stroke, whereas DBP fall confers higher risk of MI.

OBJECTIVE:: We aimed to test whether eight common recently identified single-nucleotide polymorphisms (SNPs), strongly associated with blood pressure (BP) in the population, also have impact on the degree of BP reduction by antihypertensive agents with different mechanisms. METHODS:: In 3863 Swedish hypertensive patients, we related number of unfavorable alleles of each SNP (i.e. alleles associated with higher baseline BP) to the magnitude of BP reduction during 6 months of monotherapy with either a beta-blocker, a thiazide diuretic or diltiazem. RESULTS:: For six SNPs (rs16998073, rs1378942, rs3184504, rs1530440, rs16948048, rs17367504) no pharmacogenetic interactions were suggested, whereas two SNPs showed nominal evidence of association with treatment response: PLCD3-rs12946454 associated with more SBP (beta = 1.53 mmHg per unfavorable allele; P = 0.010) and DBP (beta = 0.73 mmHg per unfavorable allele; P = 0.014) reduction in patients treated with diltiazem, in contrast to those treated with beta-blockers or diuretics wherein no treatment response association was found. CYP17A1-rs11191548 associated with less DBP reduction (beta = -1.26 mmHg per unfavorable allele; P = 0.018) in patients treated with beta-blockers or diuretics, whereas there was no treatment response association in diltiazem-treated patients. However, if accounting for multiple testing, the significant associations for rs12946454 and rs11191548 were attenuated. CONCLUSION:: For a majority of these, eight recently identified BP-associated SNPs, there are probably no important pharmacogenetic interactions for BP reduction with use of beta-blockers, diuretics or diltiazem. Whether the nominally significant associations for rs12946454 and rs11191548 are true signals and could be of possible clinical relevance for deciding treatment of polygenic essential hypertension should be further tested. (Less)

The RIAHD (Risk factor Identification and Assessment in Hypertension and Diabetes) study was conducted as a non-interventional study in 699 patients with hypertension without additional risk factors (low-risk) or with additional risk factors (high-risk), primarily diabetes and/or micro/macroalbuminuria (MA/A). The RIAHD study aimed to assess novel cardiovascular risk factors (RFs) such as blood viscosity, inflammatory markers and selected genetic polymorphisms. In addition, the RIAHD study also aimed to examine home versus office blood pressures (BPs), objective cardiovascular risk according to ESH/ESC Systematic Coronary Risk Evaluation systems (SCORE) and subjectively expressed risk (clinical judgment) by physicians and patients. The health economic impact of other RFs, associated clinical conditions and target organ damage was also studied by evaluating healthcare utilization and sick leave in high-risk patients. In terms of circulating RFs, measured and calculated whole blood viscosity did not differ between the high and low-risk patient groups. Fibrinogen was significantly increased in the high-risk group, while hsCRP did not differ between the two groups. Self-measured BPs at home differed from BPs measured in the office. The average systolic home BPs was 11.8 mmHg lower in the low-risk group and 6.7 mmHg lower in the high-risk group. The diastolic home BPs averages differed 7.1 mm Hg and 4.1 mmHg from office BPs in the low-risk and high-risk groups, respectively. A higher home BP compared with the office BP, i.e. masked high BP values, was found in 21% of patients in the low-risk group and 32% of patients in the high-risk group. Global CV risk assessment (high-risk or low-risk) by the physicians corresponded well to objective risk evaluation (ESH/ESC) in the high-risk hypertensive patients, while physicians tended to underestimate the patients CV risk in the low-risk group (without diabetes and/or MA/A). Proper global risk assessment by judgement is often difficult in cardiovascular patients. The RIAHD study emphasizes the importance of performing a more extended RF assessment in hypertensive patients with as well as without diabetes and/or micro/macroalbuminuria in order to expose the full RF profile.

To compare costs for management of hypertension in elderly hypertensives randomized to starting treatment with conventional (beta-blockers/diuretics) therapy or a therapy initiated with a calcium antagonist or an angiotensin-converting enzyme (ACE) inhibitor.Health economic substudy in the Swedish Trial in Old Patients with Hypertension-2 (STOP Hypertension-2).Outpatient clinics in Sweden. In this health economics substudy, 16/312 participating STOP-2 trial centers were selected.Elderly (70--84 years) patients (n=303) with a systolic and/or diastolic hypertension (or=180 and/or 105 mmHg).Costs for patient management were analyzed and categorized in costs for routine care (protocol-driven costs, PDC), costs for extra visits or care (non-protocol-driven costs, NPDC), and direct drug costs (drug treatment costs, DTC). All calculations are related to costs during the first year of treatment after inclusion in STOP Hypertension-2.Out of the scheduled visits, a total of 99% were actually performed by the patients. There were no differences in the number of visits between the three treatment groups (diuretics/beta-blockers, calcium antagonists or ACE inhibitors). PDC did thus not differ between the three treatment groups. NPDC were similar in the conventional and calcium antagonist groups and lower than for the ACE inhibitor group. DTC were lower in the conventional treatment group compared with the other two groups. CONCLUSION. In elderly hypertensives in STOP Hypertension-2, total costs for management of hypertension were lower in patients assigned to diuretics, beta-blockers or calcium antagonists compared with ACE inhibitors during the first year of treatment. These results may be relevant to management of elderly hypertensive patients, especially in those patients without compelling indications or contraindications to starting treatment with either of these three main drug alternatives. Notably, with a specific drug regimen there are sizable NPDC such as extra visits and controls associated with symptoms or side-effects of a specific therapy, which significantly add to the total costs of treatment. Such costs, beyond the actual costs for the drugs, are important to realize and evaluate in order to provide the true costs for treatment of hypertensive patients.

The Captopril Prevention Project (CAPPP) was designed as a prospective intervention trial comparing the effect of a treatment based on the angiotensin-converting enzyme (ACE) inhibitor captopril with that of a conventional diuretic and/or beta-blocker-based therapy, in 10,985 hypertensive patients. There was no difference in the primary cardiovascular morbidity and mortality endpoint. A lower incidence of diabetes mellitus during captopril treatment was observed in the whole CAPPP cohort that was non-diabetic at baseline (n = 10,413) as well as in such CAPPP patients that were previously untreated (n = 5033).A multivariate analysis of variables associated with the risk of developing diabetes in CAPPP demonstrated that glucose, body mass index (BMI), haemoglobin (Hb), age, 'SBP x Untreated' (the interaction between systolic blood pressure at baseline and newly diagnosed hypertension), cholesterol and prior antihypertensive treatment came out as risk factors. Based on these factors, a risk score for development of diabetes was calculated for all non-diabetic patients, who were divided into tertiles. For each tertile of risk, captopril therapy was associated with a reduced risk of diabetes development compared with conventional diuretic and/or beta-blocker therapy. When the non-diabetic cohort was divided into two subcohorts; previously treated and previously untreated patients, it turned out that the risk factors for developing diabetes differed between these two subcohorts. Only glucose, BMI and Hb came out as risk factors in all analysed cohorts.A captopril-based antihypertensive treatment regimen is associated with a lower risk of diabetes development, compared with conventional therapy based on diuretics and/or beta-blockers.

The aim of the Nordic Diltiazem (NORDIL) Study was to compare cardiovascular morbidity and mortality in calcium-antagonist-based treatment with diltiazem and conventional diuretic/beta-blocker-based treatment in essential hypertension. The objective of the present sub-study was to compare self-measured home blood pressure with office blood pressure at a time-point in the study when the patients' blood pressures had been treated to the level that the investigators conceived to be the blood pressure target. The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled 10881 patients aged 50-74 years at health centers in Norway and Sweden who had diastolic blood pressure (BP) of 100 mmHg or more. The present sub-study group (n = 87) was small but fairly representative for the entire study population regarding baseline characteristics. Both systolic (4.0 mmHg, p = 0.01) and diastolic blood pressures (3.1 mmHg, p0.001) were significantly lower at home than in the office. Pearson correlation coefficients between the respective office and home readings were statistically highly significant (p0.001), but of moderate strength ranging from r = 0.41 for heart rate to r = 0.46 and r = 0.58 for diastolic and systolic blood pressures, respectively. Altman plots also gave statistical support to some inconsistency between the two methods of measurements. Pearson correlation coefficients between afternoon and morning measurements showed strong relationships with r-values0.9 for both blood pressures and heart rate. The Altman plots also suggested excellent consistency between afternoon and morning measurements. Thus, motivated and trained hypertensive patients can perform home recordings of blood pressure and heart rate with precision; however, there are differences between recordings at home and in the investigators' offices that suggest some degree of "white coat effect" in these treated hypertensives.

(2002). Homocysteine and ADMA--emerging risk factors for cardiovascular disease? Blood Pressure: Vol. 11, No. 4, pp. 197-200.

More than 10% of patients treated for hypertension have persistently uncontrolled blood pressure (BP) despite prescription of antihypertensive drugs (1). Renal sympathetic denervation is an old con...

Aim: The aim of the present study was to examine the role of Ca2+ -mediated contractile responses in isolated mesenteric resistance arteries from rats with congestive heart failure (CHF). Methods: Heart failure was induced by ligation of the left coronary artery. Rats exposed to the same surgical procedure except ligation served as controls (Sham). The following experiments were conducted: (1) passive increase in radial stretch (the length–tension relationship) in Ca2+ -free and in depolarizing high K+- solution; (2) the contractile responses to external application of Ca2+ and high K+ -solutions in the presence of nifedipine and phentolamine; and (3) a histological evaluation of CHF and Sham vessels. Results: The length–tension induced response in Ca2+ -free buffer solution was significantly lower in arteries from CHF rats, starting at a very low tension (0.9 ± 0.2 mN/mm for heart failure and 1.7 ± 0.2 mN/mm for Sham). This difference, but at a higher degree of stretch, was also present in K+ -activated vessels. The external application of Ca2+ in K+ -depolarized vascular segments in the presence of phentolamine (1 μM) induced an enhanced contractile response in arteries from CHF rats compared with Sham (4.8 ± 0.3 mN/mm and 3.6 ± 0.6 mN/mm, respectively, P = 0.059). In the absence of phentolamine the reverse response was found (4.0 ± 0.4 mN/mm and 5.7 ± 0.3 mN/mm for CHF vs. Sham respectively, P = 0.035). Application of increasing concentrations of K+ -solution induced a stronger contractile response in Sham compared with CHF arteries (Sham 4.9 ± 0.4 and heart failure 4.0 ± 0.3, P = 0.04). Microscopic examination of vessels yielded no difference in gross morphology, media thickness or wall to lumen ratio between CHF and Sham arteries. Conclusion: The results indicate an attenuation of α-adrenoceptors and a difference of Ca2+ -mediated vascular contractility in resistance arteries of congestive heart failure rats.

In HIV patients, the increased use of highly active antiretroviral therapy (HAART) has resulted in effective suppression of virus replication, reduction of opportunistic infections and malignancies...

BackgroundThe benefits of treating hypertension in elderly diabetic patients, in terms of achieving reductions in cardiovascular morbidity and mortality, have been documented in several recent prospective trials. There has, however, been some controversy regarding the effect of different antihyperte

OBJECTIVE: To evaluate blood pressure in a population-based cohort with urographic renal scarring after childhood urinary tract infection. DESIGN: Follow-up investigation 16-26 years after the first recognized urinary tract infection. SETTING: University out-patient clinic for children with urinary infections serving the local area. PATIENTS: From the original cohort of 1221 consecutive children with first urinary tract infection diagnosed during 1970-1979, 57 of 68 with non-obstructive renal scarring participated as well as 51 matched subjects without scarring. MAIN OUTCOME MEASURE: 24 h ambulatory blood pressure. RESULTS: Acceptable blood pressure monitorings were obtained from 53 individuals with and 47 without scarring. There were no significant differences between the two groups even when only patients with the most extensive scarring (individual kidney clearance < 30 ml/min per 1.73 m2) or patients with bilateral scarring were compared with the non-scarring group. Mean systolic or diastolic blood pressure above +2 SD were found in 5/53 (9%) and 3/47 (6%) in the scarring and non-scarring group, respectively. Plasma renin activity, angiotensin II and aldosterone concentrations were not significantly different, but atrial natriuretic protein was significantly higher in the scarring group (P = 0.004). CONCLUSION: This study demonstrates a low risk of hypertension two decades after childhood urinary tract infection. It should be stressed that the patients with renal scarring were under close supervision throughout childhood. Those with scarring had higher concentrations of atrial natriuretic protein which might indicate a counter-regulation mechanism.

Early observational BP data from untreated persons undergoing insurance physicals demonstrated that mortality was directly proportional to BP, even in the normal range. However, some argued that tr...

Objective: Congestive heart failure (CHF) is accompanied by enhanced peripheral sympathetic nerve activity, increased vascular resistance and impaired peripheral blood flow. Besides noradrenaline and neuropeptide Y, the sympathetic nervous system also releases ATP, which has contractile effects mediated by different subtypes of P2-receptors on the vascular smooth muscle cells. The present study was designed to examine postsynaptic changes of the contractile responses to ATP and other extracellular nucleotides in CHF. Methods: CHF was induced by left coronary artery ligation resulting in a reproducible myocardial infarction in Sprague–Dawley rats. Contractile responses were examined in cylindrical segments of aorta and the mesenteric artery after endothelium removal. To determine if an altered response was regulated on the transcriptional level, competitive reverse transcription polymerase chain reaction (RT-PCR) was used to estimate the amount of P2X1-receptor mRNA. Results: ATP, which is both a P2X1- and a P2Y-receptor agonist, induced a weaker contraction in the mesenteric artery from CHF as compared to sham operated rats. A decrease in both potency and maximum contraction was shown for the selective P2X1-receptor agonist, αβ-MeATP, in the mesenteric artery (pEC50=6.04 vs. 5.76, C max=57% vs. 33%, sham vs. CHF operated rats), but not in the aorta. Competitive RT-PCR also revealed decreased P2X1-receptor mRNA levels in CHF operated rats in the mesenteric artery (9106·103 vs. 714·103 molecules/μg, sham vs. CHF operated rats), while it remained unaltered in the aorta. To study the P2Y-receptor induced contractile effects, the P2X1-receptors were first desensitised with αβ-MeATP (10−5 M for 8 min). After P2X1-receptors desensitisation, UTP and UDP induced strong contractions in both the mesenteric artery and in the aorta, while ATP and ADP were much less effective. These contractions were not altered by CHF, indicating that vascular contraction mediated by P2Y-receptors are unaffected by CHF. Conclusion: CHF induces downregulation of P2X1-receptor stimulated contraction in the mesenteric artery depending on decreased mRNA synthesis for the receptor, while the P2Y-receptor activity remains unchanged. Downregulation of P2X1-receptors appears to be specific for peripheral resistance arteries. This may represent a compensatory response to enhanced peripheral sympathetic nerve activity and increased vascular resistance in CHF.

In April 2007, the ESH Scientific Council has approved 65 centers in the first round of applicants, representing 13 European countries. The list of ESH Hypertension Excellence Centers was published...

OBJECTIVE The primary objective of this double-blind, parallel-group, placebo-controlled, multicentre study was to compare the antihypertensive efficacy of one versus two daily doses of eprosartan, a novel nonbiphenyl, nontetrazole angiotensin II receptor antagonist, in 243 patients with mild to moderate hypertension (sitting diastolic blood pressure > or = 95 to < or = 114 mmHg). PATIENTS AND METHODS The patients were randomized to titrated doses of eprosartan at 400-800 mg once a day, eprosartan at 200-400 mg twice a day, or placebo, with the incremental dose titrated over a 9-week period. Patients reaching target blood pressure (sitting diastolic blood pressure of < or = 90 mmHg) continued the fixed-dose treatment for 4 weeks. The primary efficacy measure was the mean change in trough sitting diastolic blood pressure from baseline to the study endpoint, determined on an intent-to-treat basis. RESULTS By the end of the study, eprosartan had significantly reduced mean trough sitting systolic and diastolic blood pressure relative to baseline and to placebo. The mean +/- SD change from baseline in diastolic pressure was -9 +/- 8.4 mmHg for the single daily dose, -9 +/- 8.5 mmHg for two doses a day and -4 +/- 8.1 mmHg for placebo (P < 0.0001 versus placebo for both eprosartan regimens). Similarly, both eprosartan regimens significantly reduced mean trough standing systolic and diastolic blood pressure. At the end of the study, the response rate in the single daily dose group (46.8%) was significantly higher than in the placebo group (25.6%). There were no significant differences between the treatment groups in the number of patients whose blood pressure responded to treatment; 41.7% of those taking eprosartan once a day and 44.4% of those taking eprosartan twice a day, and who responded to treatment, were maintained on their original starting doses. The total daily dose required to achieve target blood pressure was comparable, whether eprosartan was administered once or twice a day. Both eprosartan regimens were well tolerated and the incidence of adverse events with eprosartan was similar to that of placebo. CONCLUSIONS These results demonstrate that there was no significant difference in antihypertensive efficacy or tolerance between eprosartan taken in one or in two daily doses. Both dosing regimens provided significant and clinically meaningful reductions in blood pressure that were superior to placebo. Eprosartan in a single daily dose was shown to be an effective antihypertensive agent. Because of the good adverse-effect profile and the simplicity of a single daily dose, eprosartan has the potential to improve patient compliance.

Perceptions of effects of a medical regimen may affect patients' adherence to therapy.To assess concordance between patients' and physicians' estimations of the risks of hypertension and benefits of treatment during a regular follow-up appointment.A population-based Swedish multicentre study. Patients were included consecutively from a randomized selection of centres (55 primary health care centres and 11 clinics of internal medicine).A questionnaire was given to 1013 patients undergoing their individually prescribed antihypertensive therapy and 212 physicians who were caring for these patients.Without therapy, patients perceived the risks of cardiovascular complications to be higher than did their physicians. Patients were not aware that an increasing number of risk factors has an impact on the risk of complications. Patients furthermore rated the benefits of treatment higher than did their physicians (P0.001). Of the patients, 14% had blood pressuresor = 140/90 mmHg. Most of the patients (61%) were not aware of their target blood pressure. However, when the target pressure was communicated to patients by the physician, patients remembered it accurately. The patients were generally not willing to trade even minor side effects from antihypertensive therapy for benefits of treatment.There was a high degree of inconsistency between patients' and physicians' estimations of risks of hypertension. Patients estimated the effects of treatment to be more beneficial than did their physicians.

A large number of prospective intervention trials have clearly demonstrated that drug treatment of hypertension lower cardiovascular morbidity and mortality. In the elderly, where treatment results in higher absolute decreases in morbidity and mortality, drug treatment is clearly cost-effective or even cost-saving in some groups of patients. Although the concept of treating hypertension is generally well accepted, a significant portion of patients remain insufficiently treated. In spite of major advances in the management of hypertension during the last decades, there is an excess morbidity and mortality in the hypertensive population. Thus, treatment is still imperfect, and a number of measures need to be taken in order to bring down cardiovascular risk in hypertensive patients to that of the normotensive population.

Hypertension is an established risk factor for cardiovascular disease morbidity and mortality. Randomized trials of antihypertensive therapy have demonstrated the benefits of treating diastolic blood pressure, and recently the value of treating isolated systolic blood pressure has also been established. There is an excess risk of cardiovascular disease in subjects with borderline isolated systolic hypertension. In fact, data from men screened for the Multiple Risk Factor Intervention Trial show that the great majority of excess deaths are in those with high-normal systolic blood pressure or with stage 1 hypertension, i.e., systolic blood pressure 130 to 159 mmHg. Similarly, data from the Framingham Heart Study and the Physicians' Health Study emphasize the importance of mild elevations of systolic blood pressure. As age increases the hemodynamic patterns of blood pressure change due to an increase in large artery stiffness, and borderline isolated systolic hypertension becomes the dominant form of hypertension. These facts make the prevention and control of borderline isolated systolic hypertension a key strategic challenge in the effort to prevent excess mortality attributable to blood pressure levels above normal.

Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of β-endorphin (BE) during control pacing (8 ± 22%) changed to release at the maximum pacing rate during treatment (–21 ± 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.

There is an increasing recognition that there are gender specific characteristics of cardiovascular disease, the commonest cause of death in most developed countries [1,2]. Men and women differ con...

We evaluated 30 consecutive patients and 48 age- and sex-matched controls to explore the possibility of a pathogenic contribution by plasma endothelin-1 in the cardiac expression of systemic sclerosis. Venous plasma endothelin-1 was measured by radio-immunoassay and left ventricular function by echocardiography. The patient group had elevated plasma endothelin-1 (2.6 +/- 0.2 vs. 1.8 +/- 0.1 pmol/1, P < 0.001), but endothelin-1 was not related to age, heart rate, blood pressure, total peripheral resistance, disease duration or systemic sclerosis score. Endothelin-1 was related to left ventricular hypertrophy in terms of septal thickness (r = 0.33, P < 0.01) and left ventricular mass index (r = 0.32, P < 0.01). Plasma endothelin-1 was further related to measures indicating reduced left ventricular filling; left atrial emptying index (r = -0.50, P < 0.0005), the first third filling fraction (r = -0.31, P < 0.05) and the time velocity integral of Doppler early/late filling velocity (r = -0.40, P < 0.001). Furthermore, circulating endothelin-1 was related to impaired left ventricular contractility as estimated by pre-ejection period/left ventricular ejection time (r = 0.32, P < 0.01) and end-systolic wall stress/volume index (r = -0.30, P < 0.05). We conclude that plasma endothelin-1 is elevated in relation to the degree of left ventricular hypertrophy, diastolic dysfunction and impaired contractility in systemic sclerosis. It may be of pathogenic importance to the cardiac involvement in systemic sclerosis which is not mediated via an increase in systemic blood pressure. It is not yet clear whether our findings are exclusive to systemic sclerosis patients or represent a generalized phenomenon in patients with impaired left ventricular function.

In order to assess the effects of dihydropyridine calcium antagonist on sympathetic nerve activity (SNA) in experimental chronic heart failure (CHF), felodipine was given to rats with CHF induced by coronary artery ligation. Anesthetized CHF (n = 7) and sham-operated (n = 9) rats were injected with a bolus dose of felodipine (20 µg/kg) and then infused with felodipine (30 µg/kg/h) for 3 hours. Control CHF rats (n = 8) were given vehicle in the same way. After felodipine treatment, mean blood pressure (MBP) rapidly decreased to 75–85 mmHg, and there was a reflex tachycardia and reflex activation of renal SNA. The heart rate (HR) had returned to baseline level after 3 hours of continuous felodipine infusion, and the SNA returned to baseline level after 2 hours of infusion. At the end of the experiment, renal SNA was 65.4 ± 11.5% of the baseline level in CHF rats receiving felodipine (P 0.05), but there was no statistical difference between the two groups. Arterial baroreceptor sensitivity (assessed by phenylephrine infusion), which was impaired in CHF rats (−2.7 ± 0.2 SNA%/mmHg in all CHF rats together vs. −3.6 ± 0.4 in sham-operated rats, P < 0.5) did not differ significantly from that in sham-operated rats during felodipine infusion (−3.2 ± 0.4 in felodipine-treated CHF rats vs. −3.7 ± 0.6 in sham-operated rats) but deteriorated without felodipine treatment (−2.1 ± 0.3 in CHF rats receiving vehicle, P < 0.05). The biphasic renal SNA response during felodipine infusion suggests that felodipine does not cause persistent sympathetic activation and relatively improves baroreceptor sensitivity in CHF rats.

Objective To study the effects of the selective neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226 in spontaneously hypertensive rats (SHR) in order to elucidate whether NPY function may be altered in the SHR and whether the NPY Y1 receptor plays a specific role in the maintenance of high blood pressure in this genetic form of hypertension. Methods Pithed and conscious SHR were studied after intravenous administration of 0.125-1 mg/kg BIBP 3226. The cardiovascular effects were evaluated under baseline conditions, under acute stress and after exogenous administration of 20 microg/kg NPY. The potentiating effects of NPY on pressor responses to phenylephrine and tyramine were studied in the SHR. Results Intravenous administration of 0.125-1 mg/kg BIBP 3226 dose-dependently inhibited the pressor response to exogenous NPY in pithed SHR. At higher doses BIBP 3226 had an effect duration of 20-40 min. In the pithed SHR, a 0.5 mg/kg bolus injection of BIBP 3226 shifted the pressor response curve for exogenous NPY significantly to the right It also inhibited significantly the potentiating effects of NPY on pressor responses to phenylephrine and tyramine. In conscious SHR, 0.125-1 mg/kg BIBP 3226 did not reduce the basal blood pressure. In combination with a hypotensive dose of prazosin, administration of 0.5 mg/kg BIBP 3226 had no added effects lowering the basal blood pressure. A stressful stimulus, namely an air jet, caused a brief increase in blood pressure and heart rate in the conscious SHR. In this model, 0.5 mg/kg BIBP inhibited the heart rate response slightly but had no effect on the blood pressure response. Conclusions Our results demonstrate that, although the selective NPY Y1 receptor antagonist BIBP 3226 may shift the pressor response to exogenous NPY potently, it does not influence basal blood pressure significantly in the SHR.

An updated 2013 version of the European Hypertension Guidelines is now jointly issued by the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) (1,2). Importantly, ...

OBJECTIVE: The brain derived neurotrophic factor (BDNF) locus has been implicated in psychiatric and substance related disorders. Recent genome-wide association studies (GWAS) have shown strong associations between single nucleotide polymorphisms in BDNF, smoking behaviour and high body mass index (BMI). Our aim was to test whether genetic BDNF variation alters the risk of smoking related morbidity and mortality. DESIGN: Cox proportional hazards models were used to relate the BDNF rs4923461(A/G) polymorphisms to all-cause, cancer and cardiovascular mortality and cardiovascular disease (CVD) incidence adjusted for age, sex, BMI, and smoking quantity. SETTING: The Malmö Diet and Cancer Study (MDCS), a population based prospective cohort study (n=30 447). PATIENTS: We obtained complete data on 25 071 subjects, of whom 6507 were current smokers and 18 564 were non-smokers who underwent a baseline examination from 1991-1996. MAIN OUTCOME MEASURES: During a mean follow-up time of 12 years, 1049 deaths (346 cardiovascular deaths and 492 cancer deaths) and 802 incident CVD events occurred among current smokers. RESULTS: The major allele (A) of rs4923461 was significantly associated with ever having smoked (p=0.03) and high BMI (p=0.001). The A-allele was associated with risk of all-cause (HR=1.12, 95% CI 1.00 to 1.25; p

To describe the localization of pain in consecutive patients admitted to the coronary care unit for possible acute myocardial infarction (AMI) and to relate it to the development of AMI, age, and gender.Prospective evaluation.Sahlgrenska Hospital, covering half the area of the city of Göteborg, with half a million inhabitants.Nine hundred three consecutive patients admitted to the coronary care unit for possible AMI between 24 and 87 years old with a mean age of 64 years.Localizations of pain according to a self-constructed figure. Patient were approached between 1 and 14 days after onset of symptoms and asked to describe the localization of pain according to the figure, including nine positions on the chest, left and right arm, neck, and back.AMI developed in 50% of patients during the first 3 days in hospital. Patients in whom AMI developed localized their pain to an extent similar to those without AMI in seven of nine chest areas. However, patients with AMI reported pain in the upper right square of the chest more frequently (p0.001) and in the middle left square of the chest less frequently (p0.01) than did patients without AMI. Pain in both the right (p0.001) and left arms (p0.01) was more frequently reported by patients who had AMI. Among patients with AMI, women reported pain in the neck (p0.05) and in the back (p0.01) more frequently than did men. Compared with elderly patients, younger patients reported pain more frequently in the left arm (p0.01), right arm (p0.01), and neck (p0.05).Among consecutive patients with possible AMI admitted to the coronary care unit, patients who had confirmed AMI reported pain in both arms more frequently than did patients without AMI. However, both groups described their chest surface distribution of pain similarly in the majority of positions, thereby indicating that the localization of chest pain is of limited use in predicting which patients will eventually have AMI.

Objective: Vascular alpha-2 adrenoceptor function of rats with congestive heart failure (CHF) was characterized in both in vivo and in vitro experiments. Methods: CHF was induced in Sprague-Dawley rats by coronary artery ligation. Sham-operated rats served as normal controls. Postjunctional alpha-2 adrenergic responsiveness was assessed in vivo using the pithed rat model and in vitro in organ bath. Vascular alpha-2 adrenoceptor density was studied by receptor binding assay. Results: Four to 6 weeks after this surgical procedure, plasma catecholamines were markedly increased in CHF rats. In vivo vascular responses to alpha-2 adrenoceptor agonists BHT933 and clonidine were significantly decreased in CHF rats ( P < 0.001). Clonidine elicited dose-dependent responses in endothelium intact mesenteric arteries in both CHF and sham-operated rats. The dose-response curve in CHF was shifted to the right with a pD2 value of 5.5 ± 0.2 compared with control rats 6.2 ± 0.2 ( P < 0.05). The response to clonidine was selectively blocked by an alpha-2 adrenergic antagonist rauwolscine in both groups. Endothelium denuded arteries showed an enhanced response to clondine in both CHF and control rats. However, the response to clondine is still decreased in CHF compared to sham-operated rats ( P < 0.05). Alpha-2 adrenoreceptor density, as determined by [3H]yohimbine binding in membrane preparations from mesenteric arteries was decreased in CHF compared to sham-operated rats (Bmax 43 ± 6 vs. 104 ± 20 fmol/mg protein, P < 0.05). Conclusions: Vascular alpha-2 adrenoceptor function is decreased in rats with CHF.

The objective was to evaluate the dose-related efficacy/tolerance profile of 240, 300, 360, and 420 mg diltiazem slow-release, once-daily (OD) doses, with emphasis on the 300 mg dose. The study was randomized and double-blinded with a 36-week parallel, two-branched, cross-over design after a single-blind, run-in period of 4 weeks on placebo and 6 weeks on 300 mg diltiazem OD. Each branch included six 6-week active treatment periods with 180, 240, and 300 mg tablets, one or two tablets OD. Participants were men and postmenopausal women, aged 40-70 years, with uncomplicated primary hypertension (WHO stages I and II) and a supine diastolic blood pressure of 95-115 mm Hg in the absence of antihypertensive medication. A total of 138 patients from various clinics participated in the study. All were included in the intention to treat analysis, and 117 patients were included in the per protocol analysis. Criteria for evaluation were blood pressure, heart rate, and response rate, as well as plasma diltiazem and metabolite M1 concentration before morning dose. Well-being of the patients and adverse events were recorded. Electrocardiogram and standard laboratory tests were obtained. Analysis of variance was used for statistical calculations. Supine blood pressures and response rates in the per protocol analysis were 161.2/97.0 for placebo (29.1%), 155.2/ 92.8 for 240 mg (54.7%), 153.8/91.6 for 300 mg (55.6%), 155.5/92.0 for 360 mg (59.0%), and 152.0/90.5 for 420 mg (63.2%) of diltiazem OD. The intention to treat analysis was very similar to the per protocol analysis. There was a small but statistically significant decrease in heart rate for all doses of diltiazem OD compared to placebo. A linear relationship existed between the dose and the plasma concentration of both diltiazem and metabolite M1, as well as a dose-response relationship. Diltiazem OD in the dose range 240-420 mg was generally well tolerated and not differently perceived from the placebo treatment except for ankle edema (2-6%). The study shows that OD diltiazem is significantly superior to placebo for mild to moderate hypertension and that the effect is large enough to be clinically valuable. It also shows that there is a linear dose-response relationship for diltiazem between 240 and 420 mg.

Sinus arrest or atrioventricular block are rare but serious adverse effects of diltiazem. The risk of developing such adverse reactions may be somewhat exacerbated by concomitant beta-adrenergic blocker therapy. In patients with hypertension or coronary heart disease, combination therapy with diltiazem and a beta-blocker usually enhances therapeutic benefit relative to monotherapy, but adverse effects attributable to this combination, especially in patients with left ventricular dysfunction or latent cardiac conduction deficits, may be limiting. Therefore, such combination therapy may not be suitable in patients with atrioventricular block grade I, bradycardia or hypotension, and patients on the combined therapy should always have their blood pressure, heart rate and atrioventricular conduction on ECG monitored. If combination therapy with diltiazem and propranolol or metoprolol is commenced, or in the case of impaired renal function, an adjustment of the beta-blocker dosage may be required. Clinical studies on the combined use of diltiazem and beta-adrenergic blockers mostly concern the treatment of angina pectoris in patients with coronary heart disease. Although very few cases of severe bradycardia and conduction abnormalities have been reported in patients with uncomplicated hypertension on diltiazem and beta-blockade combination, there seems to be a potential for the occurrence of significant conduction disturbances with the combined treatment, and precautions should apply also for hypertensive populations.

In addition to its direct vasoconstrictive effect, neuropeptide Y (NPY) potentiates noradrenaline-(NA) induced contraction and inhibits acetylcholine-(ACh) induced relaxation: The aim of the present study was to elucidate the NPY receptor subtypes responsible for mediating these three responses. NPY, peptide YY (PYY) and pro34NPY (a NPY Y1 receptor agonist) induced equipotent and equally strong concentration-dependent contractions of guinea pig basilar arteries. NPY13-36 (a NPY Y2 receptor agonist), however, caused only weak contraction with significantly lower potency. The NPY-induced contraction was significantly inhibited by the selective NPY Y1 receptor antagonist BIBP3226 (1 microM). NPY, PYY and pro34NPY but not NPY13-36 significantly potentiated the NA-induced contraction in guinea pig mesenteric arteries. The potentiation was significantly inhibited by BIBP3226 (1 microM). In precontracted guinea pig basilar arteries, ACh induced a concentration-dependent relaxation which was significantly inhibited by NPY, PYY and NPY13-36 but not by pro34NPY. BIBP3226 had no significant effect on the NPY-induced inhibition of the relaxation. These results suggests that the NPY Y1 receptors mediate the direct contraction and the potentiation of the NA-induced contraction but not the inhibition of the ACh-induced relaxation. This effect seems to be mediated by another NPY receptor subtype, presumably by the Y2 receptor, as judged from the agonist potency order.

The Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-2) was designed by a project group of the Swedish Hypertension Society to test whether the "newer" treatment alternatives (ACE inhibitors and calcium antagonists) are as good as, better or less good than, the "older" ones (beta-blockers and diuretics) in terms of preventing cardiovascular morbidity and mortality in elderly hypertensives. The aim of the present paper is to report on the progress of the study.Prospective, open trial with blinded end-point committee and centralized randomization (PROBE design). STOP-Hypertension-2 may be regarded as a scientific follow-up of the previously published Swedish Trial in Old Patients with Hypertension (STOP-Hypertensioon-1) (6) using the same study organization.By the end of 1994 when recruitment was stopped, 6628 hypertensive men (34%) and women (66%) aged 70-84 (mean age 76) had been included at 312 Swedish health centres (out of approximately 850). In the whole cohort 11% are diabetics and 9% smokers. The mean total cholesterol value is 6.5 mmol/L.In the whole study cohort, blood pressure was lowered from 194/98 mmHg to 167/85 mmHg after one year. At the end of 1995, 319 fatal events (all-cause mortality) had been reported, corresponding to a mortality rate of 21.3 per 1000 person-years.In STOP-Hypertension-2, 6628 elderly hypertensive have been randomized to three different treatment regimes: beta-blocker+diuretics (the active treatment arm in STOP-Hypertension-1), ACE inhibitors, or calcium antagonists. Their average lowering of blood pressure was 27/13 mmHg and end-points have occurred at the expected rate. Thus, it should be possible to terminate STOP-Hypertension-2 within two to three years.

We related atrial natriuretic peptide (ANP) among 30 consecutive patients with systemic sclerosis (SScl) and 48 gender- and age-matched controls to the measurements of left ventricular (LV) function as evaluated by echocardiography and external pulse curves to determine possible causative factors for an increased level of plasma ANP. The patients had a markedly elevated plasma ANP level (239.4 +/- 59 vs. 178.2 +/- 36 pmol/l, p < 0.0005), which was not related to LV systolic function, heart rate, or blood pressure. Patients had LV hypertrophy and plasma ANP correlated directly to interventricular septal thickness (r = 0.41, p < 0.005), LV posterior wall thickness (r = 0.32, p < 0.01), and wall thickness to cavity dimension (r = 0.44, p < 0.0005), LV mass index (r = 0.40, p < 0.005). LV early filling properties were impaired, with reduction of atrial emptying index (p < 0.0005) and increased contribution of atrial contraction to LV filling. Plasma ANP correlated to atrial emptying index (r = 0.41, p < 0.0005) and to apex-cardiographic a wave (r = 0.28, p < 0.05). Plasma ANP was also related to left atrial dimension index (r = 0.27, p < 0.05), and was still related to atrial emptying index, but not to left atrial dimension, when considering the degree of LV hypertrophy in multivariate analysis. We conclude that ANP is elevated in patients with SScl. Reduced LV compliance, probably due to increased fibrosis, may cause changes in atrial pressure sufficient to stimulate ANP production without systolic dysfunction as a prerequisite.

(2003). Masked hypertension – a new entity and challenge for clinical hypertension research and management. Blood Pressure: Vol. 12, No. 5-6, pp. 261-263.

Epidemiological estimates (1,2) indicate that more than a quarter of the adult world population are hypertensive: an approximate one billion people with diagnosed and undiagnosed hypertension, a fi...

(2002). Blood Pressure Measurement: A Century of Achievements and Improvements in the Year 2002. Blood Pressure: Vol. 11, No. 6, pp. 325-327.

The Scandinavian countries have for many years practiced compulsory military service; in this context all 18-year-old men are subject to an extensive medical examination prior to enlistment. High blood pressure detected under such conditions is highly reproducible (1), and markers of stress such as elevated blood pressure, heart rate and plasma catecholamines during mental stress testing are reproducible many years later in the same population (2). Such stress markers predict the development of hypertension (3), weight gain (4) and insulin resistance (5) in middle age, suggesting that these pathophysiological mechanisms detected in early adulthood may underlie the development of cardiovascular disease later in life. A large national study of total mortality, cardiovascular mortality and non-cardiovascular mortality in 1.2 million men in Sweden who underwent military conscription examinations between 1969 and 1995 at a mean age of 18.4 years and were followed for a median of 24 (range 0 – 37) years has recently been reported (6). During follow-up, 28 934 (2.4%) men died. The relation of systolic blood pressure to total mortality was U-shaped, with the lowest risk at a systolic blood pressure of about 130 mmHg. This pattern was driven by the relation to non-cardiovascular mortality, whereas the relation to cardiovascular mortality increased monotonically (higher risk with higher blood pressure). There was also a relation between diastolic blood pressure and mortality risk, which in fact was stronger than that of systolic blood pressure, in terms of both relative risk and population attributable fraction (deaths that could be avoided if blood pressure was in the optimal range). Relations to cardiovascular and non-cardiovascular mortality were similar, with an apparent risk threshold at a

The debate on the risk of cancer in hypertensive patients (1–9) as well as any relationship to antihypertensive drugs (9–17) has been ongoing for decades.Firstly, the association between hypertensi...