Anne Pauline Schroeder

Small artery structure is an independent predictor of cardiovascular events in essential hypertension.

Objective Structural abnormality of resistance arteries is a characteristic pathophysiological phenomenon in essential hypertension and can be assessed in vitro as an increase in the media: lumen ratio (M: L) of isolated small arteries. We have investigated whether M: L is a risk predictor in uncomplicated essential hypertensive patients. Recently, high M: L was demonstrated as a prognostic marker in patients at high cardiovascular risk, including normotensive type 2 diabetic patients. Since diabetes is associated with pressure-independent changes in M: L, the relevance of this finding to essential hypertension has been uncertain. Methods We conducted a follow-up survey of 159 essential hypertensive patients, who had previously been submitted to a M: L evaluation while participating in a clinical trial. They composed a homogeneous moderate-risk group, with no concomitant diseases, and represented 1661 years of follow-up. Results Thirty patients suffered a documented predefined cardiovascular event during follow-up. Increased relative risk (RR) was associated with M: L ≥ 0.083 (mean level of the hypertensive cohort), RR = 2.34 [95% confidence interval (CI) 1.11–4.95], and with M: L ≥ 0.098 (mean level of a normotensive control group + 2SD), RR = 2.49 (95% CI 1.21–5.11). Both results remained significant (RR = 2.19, 95% CI 1.04–4.64, and RR = 2.20, 95% CI 1.06–4.56, respectively) when adjusted for Heart Score level (10-year mortality risk-estimate, integrating age, gender, systolic blood pressure, cholesterol and smoking). Conclusion Abnormal resistance artery structure independently predicts cardiovascular events in essential hypertensive patients at moderate risk.

Small artery structure during antihypertensive therapy is an independent predictor of cardiovascular events in essential hypertension.

Objective: Structural changes of small resistance arteries occur early in the disease process of essential hypertension and predict cardiovascular events in previously untreated patients. We investigated whether on-treatment small artery structure also identifies patients at elevated risk despite normalization of blood pressure (BP). Methods: We conducted a long-term follow-up survey of cardiovascular events in 134 moderate-risk patients with 9–12 months of well treated essential hypertension. All participants underwent subcutaneous biopsies with determination of small artery structure in terms of media to lumen ratio (M : L) before and during treatment. Results: After 9–12 months of treatment SBP was lowered from 164 ± 15 to 134 ± 14 mmHg (P < 0.01) and M : L reduced from 0.084 ± 0.028 to 0.075 ± 0.024 (P < 0.01). Mean follow-up hereafter was 15 years representing a total of 2035 years for the entire cohort. During this period 47 patients suffered a predefined cardiovascular event. For patients with on-treatment M : L above the mean value of the cohort (≥0.075), the hazard ratio was 2.14 [95% confidence interval (CI) 1.19–3.84, P = 0.01] and also those with M : L above mean +2SD of a normotensive population (≥0.098) had an elevated risk (hazard ratio 2.99, 95% CI 1.60–5.58, P < 0.01). Both results were adjusted for heart score (a 10-year mortality risk estimate integrating age, sex, smoking status, cholesterol level and SBP). Analysis of changes in M : L during treatment showed significantly higher event rates among patients with increased M : L and vice versa (hazard ratio 1.36 per 25% change, 95% CI 1.07–1.73, P = 0.013). Conclusion: On-treatment small artery structure identifies individuals still at increased cardiovascular risk despite long-term BP normalization and may be an additional target for therapy to prevent cardiovascular events.

Coronary Arteries: Magnetic Resonance Imaging Seems Safe in Patients with Intracoronary Stents

We elucidated whether exposure to cardiac magnetic resonance imaging (MRI) of patients with implanted intracoronary stents is associated with increased risk of stent-thrombosis, stent-restenosis, or other cardiovascular complications. Forty-seven patients admitted with acute myocardial infarction (AMI) were studied. Twenty-three were included in a serial cardiac MRI study, using 1.5-T scanners with standard gradient systems. The remaining patients were control subjects who were matched for age and gender with the MRI group. All patient had intracoronary stents implanted in connection with primary angioplastic treatment (PTCA) of AMI (n = 21), secondary PTCA procedures due to recurrent angina (n = 22), or both (n = 4). In the MRI group (n = 23, aged 58 +/- 10 yr), MRI was carried out one to five times in each patient a median of 166 days (range, 1-501) after stent implantation. The control group comprised 24 patients, ages 59 +/- 11 yr. The incidences of stent-thrombosis, stent-restenosis, and other cardiovascular complications did not differ statistically significantly between the two groups. In the MRI group, stent-related thrombosis (n = 1) or restenosis (n = 7) was observed in eight cases a median of 102 days (range, 7-547) after MR examination and a median of 318 days (range, 138-713) after stent implantation, compared with nine cases in the control group (thrombosis, n = 1; restenosis, n = 8) observed a median of 147 days (range, 1-267) after stent implantation. No acute thromboembolic or other complication occurred in immediate connection with MRI. The follow-up time was 21.3 +/- 4.5 months. This small study shows no evidence of an MRI-related risk of stent-restenosis or other cardiovascular complications, not even if cardiac MRI is performed early after stent implantation.

Normalization of Structural Cardiovascular Changes During Antihypertensive Treatment with a Regimen Based on the ACE-inhibitor Perindopril

Untreated essential hypertension is associated with left ventricular hypertrophy (LVH) and structural changes in resistance vessels. The aim of this study was to establish the effect of perindopril based antihypertensive therapy on media thickness to lumen diameter (media:lumen) ratio of peripheral resistance vessels and left ventricular mass in essential hypertension. Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were treated with perindopril. Insufficient treatment response (DBP > 90 mmHg) led to addition of isradipine, and hydralazine was used as a tertiary drug if necessary. Gluteal subcutaneous biopsies were taken surgically at baseline and after 9 months of successful treatment. Two small resistance arteries were isolated and mounted in a small vessel myograph, and media:lumen ratio (%) was measured under standardized conditions. Left ventricular mass was determined by echocardiography. Mean (SD) media:lumen ratio decreased from 9.8 (2.6) % to 7.8 (1.9) % (p < 0.05), while left ventricular mass decreased from 299 (75) g to 199 (53) g (p < 0.001). Correlation was found between changes in left ventricular mass index and media:lumen ratio (r = 0.62, p < 0.01). It is concluded that a perindopril based regimen efficiently normalizes resistance artery structure and left ventricular hypertrophy in essential hypertension within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension remains to be investigated.

Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial

Background: Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. Method: We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). Results: We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [−6.2 ± 18.8 mmHg (RDN) vs. −6.0 ± 13.5 mmHg (SHAM)] and at 6 months [−6.1 ± 18.9 mmHg (RDN) vs. −4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)]. RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Conclusion: Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Serial magnetic resonance imaging of global and regional left ventricular remodeling during 1 year after acute myocardial infarction.

Biplane long-axis cine MRI was performed in 51 patients 1, 13, 26, and 52 weeks after their first AMI. LV mass index (LVMI) was significantly increased 1 week after AMI (84.3 ± 16.9 vs. 68.1 ± 11.4 g/m2 controls, n = 48, p < 0.001), presumably owing to edema of the infarcted myocardium. Six months after AMI, LVMI decreased to 76.5 ± 16.4 g/m2, but had again augmented after 1 year (81.8 ± 17.3 g/m2, p < 0.05), suggesting late, compensatory left ventricular hypertrophy. In patients treated with primary percutaneous transluminal coronary angioplasty, LVMI decreased 5% over 1 year, while LVMI increased 10% in patients receiving thrombolysis (p < 0.05). In the entire population, the global increase in LVMI 1 year after AMI seemed to reflect global cavity dilatation with unchanged thickness of the vital myocardium. In conclusion, in patients receiving contemporary treatment, LV remodeling only partially complied with the classical patho-anatomical concept.

Effect of antihypertensive treatment on cardiac and subcutaneous artery structure: a comparison between calcium channel blocker and thiazide-based regimens.

The effects of two antihypertensive regimens (isradipine and hydrochlorothiazide-amiloride) on the ratio between media thickness and lumen diameter of subcutaneous arteries and on left ventricular mass in essential hypertension were compared. Fifty patients, aged 46.3+/-8 (mean+/-SD) years, with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with either isradipine or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added in both groups as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. A subcutaneous gluteal biopsy was taken surgically before medication and again after 9 months of successful antihypertensive treatment. Two small resistance arteries were isolated from each biopsy and mounted in a Mulvany-Halpem isometric small vessel myograph. The media thickness-to-lumen diameter ratio (percentage) of the vessels was measured under standardized conditions and meaned. Left ventricular mass (LVM) index was determined by echocardiography according to the Penn convention. Ten patients were treated with isradipine as monotherapy, whereas only one patient was well controlled on diuretics as monotherapy. Mean blood pressure was reduced equally with the two regimens, from 131+/-9 mm Hg to 101+/-10 mm Hg with the isradipine and from 128+/-9 mm Hg to 99+/-7 mm Hg with the thiazide/atenolol regimen. LVM decreased significantly in both groups by 130+/-75 g with the isradipine-based regimen and by 70+/-53 g with the hydrochlorothiazide/atenolol-based regimen. The reduction of LVM was significantly greater on the isradipine-based regimen than on the thiazide-based regimen (P < .01). There was a significant reduction of media thickness-to-lumen diameter ratio during treatment with the isradipine-based regimen from 10.9% to 8.8% (P < .01). The reduction in the thiazide regimen was from 9.7% to 8.5%, which was not significant (P = .07). The study demonstrated significant reduction of hypertensive changes in peripheral resistance artery structure during antihypertensive treatment with an isradipine-based regimen. The thiazide/betablocker-based regimen did not have a significant effect on the vessels. Significant reduction of LVM was achieved with both isradipine-based and thiazide/atenolol-based regimens. The reduction of LVM obtained with the isradipine-based regimen was significantly greater than that of the thiazide/atenolol-based regimen.

Influence of Humoral and Neurohormonal Factors on Cardiovascular Hypertrophy in Intreated Essential Hypertensives

In essential hypertension, cardiovascular structure is believed to be influenced by hormonal and by hemodynamic factors. The objective of the present study was, in essential hypertensives, to investigate the relationship between blood pressure (BP) level as well as circulating hormones on the one hand and cardiovascular structure on the other. Seventy-nine untreated essential hypertensives were examined by 24-h ambulatory BP monitoring, echocardiography, microscopy of subcutaneous resistance vessels and analyzes of plasma for angiotensin II (P-Ang II), aldosterone, atrial natriuretic factor and 24-h urinary excretion of catecholamines. Multiple regression analysis showed a statistically significant correlation between P-Ang II and the end diastolic interventricular septal diameter (IVSDd) (R = 0.32, P = .005) and a weak correlation between P-Ang II and the left ventricular posterior wall diameter (R = 0.22, P = .049). These correlations were closer in the subgroup of patients (N = 54) who had never received antihypertensive treatment (R = 0.42/0.32, respectively). A weak, though statistically significant, correlation was found between the catecholamine excretion and systolic BP (R = 0.26, P = .03). A statistically negative correlation existed between catecholamines and end-diastolic left ventricular internal diameter index (R = -0.36, P = .001). No significant relationship was found between hormonal levels and the tunica media structure of the resistance arteries. In conclusion, P-Ang II was in this study significantly correlated to IVSDd, but not to resistance artery structure. In essential hypertension a complex relationship exists between humoral and hemodynamic factors and cardiovascular remodeling.

Heart function in patients with chronic glomerulonephritis and mildly to moderately impaired renal function. An echocardiographic study.

UNLABELLED Left ventricular hypertrophy and diastolic heart dysfunction have been reported in essential hypertension and in patients with chronic renal failure, treated with haemodialysis, but a close association with blood pressure (BP) level has not been uniformly documented. Thus, other factors could be involved in the pathogenesis of cardiac dysfunction. The aims of the present echocardiographic study were to investigate cardiac morphology and function in patients with chronic glomerulonephritis with mildly to moderately impaired renal function, and to study the relation between echocardiographic findings and glomerular filtration rate (GFR), BP and age. Twenty patients with chronic glomerulonephritis and 14 healthy controls, of the same age- and sex-distribution, were examined by 2D-, M-mode and pulsed-wave Doppler echocardiography. In patients, GFR was determined as plasma clearance of Cr-EDTA. The patients had significantly thicker left ventricular (LV) posterior walls in end diastole (8.7 vs 8.1 mm, p < 0.05), and a higher LV mass index (106.5 vs 93.8 g/m2, p < 0.05). Systolic functional indices, i.e. LV fractional shortening and LV ejection fraction, were statistically significantly lower in patients than in controls (p < 0.05). LV diastolic function in patients was characterized by a statistically significantly lower early peak flow velocity (E-Vmax) (0.66 compared with 0.8 m/s) and early to late peak flow velocity ratio (E/A ratio) (1.07 vs 1.41), as well as E/A ratio of time velocity indices (VTI-E/A) (1.45 vs 1.99) (p < 0.05). The right ventricular filling indices showed a tendency towards a lower E-Vmax in patients (0.55 compared with 0.62 m/s, p = 0.1). In patients, statistically significant negative correlations were found between age and mitral E/A ratio (r = -0.76, p < 0.0001), as well as LV VTI-E/A(r = -0.81, p < 0.0001). The same trend was seen for the tricuspid E/A ratio. No statistically significant correlations were found in patients between mitral or tricuspid E/A ratio and GFR, BP, LV mass or heart rate. IN CONCLUSION in a group of patients with chronic glomerulonephritis and mildly to moderately impaired renal function, it was found by means of echocardiography that there was a higher LV mass index and decreased systolic function, when compared with healthy controls. In addition, the patients had diastolic dysfunction of primarily the left ventricle. The echocardiographic findings were not correlated to BP level or renal function. This suggests that factors other than GFR or BP per se might be involved in the pathogenesis of cardiac dysfunction, at an early stage.

Intraventricular dispersion and temporal delay of early left ventricular filling after acute myocardial infarction. Assessment by magnetic resonance velocity mapping

This article aims to describe early left ventricular diastolic inflow using magnetic resonance velocity mapping in patients with recent acute myocardial infarction and in normal volunteers. Magnetic resonance velocity mapping was performed in a long axis plane through the hearts of 46 patients with recent, first time acute myocardial infarction and 43 age-matched normal volunteers. The peak velocities at six levels of the early diastolic inflow stream were recorded. A velocity index was calculated as the peak velocity in each position relative to the peak velocity at the mitral leaflet tips. Also, the temporal delay of velocity propagation was computed. Velocity index 4 cm downstream of mitral leaflet tips was lower in the acute myocardial infarction group (0.42 (0.17)) (mean (SD)) compared to controls (0.59 (0.25)) (p < 0.001). Temporal delay in the same position was longer in the acute myocardial infarction group (62 (67) ms) than in controls (32 (39) ms) (p < 0.02). Blood flow patterns in patients after acute myocardial infarction were characterized by increased dispersion of velocities and increased temporal delay of velocity propagation, probably reflecting impaired active left ventricular relaxation. Intraventricular flow measurements constitute a promising new technique for non-invasive assessment of left ventricular diastolic function.