Difficulty and importance of diagnosing stenosis of renal branch artery in fibromuscular dysplasia: a case report.

A 16-year-old patient presented with abdominal pain and sustained hypertension. Thorough evaluation including renography with and without captopril and renal vein renin sampling were normal. Duplex ultrasound, however, raised suspicion of a renal artery stenosis. This was confirmed by computed tomography angiography which showed a severe branch artery stenosis with post-stenotic dilatation consistent with focal fibromuscular dysplasia (FMD). As the hypertension was resistant to 3 classes of antihypertensive treatment, percutaneous transluminal renal angioplasty (PTRA) was offered. The procedure had immediate effect on the blood pressure. Without medication the patient remains normotensive 4 years after and the abdominal pain has only sporadically returned. The presented case illustrates the challenging process of diagnosing FMD-related renal branch artery stenosis as well as the potential benefits of PTRA in this patient group.

The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study.

OBJECTIVE: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. METHODS: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of ≥145 mm Hg, and/or a daytime diastolic ABPM of ≥95 mm Hg after witnessed drug intake (including ≥3 antihypertensive drugs, preferably including a diuretic). RESULTS: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety. CONCLUSIONS: This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.

The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial).

OBJECTIVES: To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension. METHODS: ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity FlexTM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor®-device. RESULTS: Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. -0.6 ± 1.3 (RDN) m/s), systolic C-BP (-2 ± 17 (SHAM) vs. -8 ± 16 (RDN) mmHg), diastolic C-BP (-2 ± 9 (SHAM) vs. -5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN. CONCLUSIONS: In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.

Residual small artery impairment in hypertensive patients with normal albumin-creatinine ratio.

Objectives Previous studies have suggested that urine albumin excretion (UAE) mirrors generalized vascular damage; however, it is unclear to which degree UAE mirrors small artery impairment. Design We enrolled 67 patients with uncomplicated essential hypertension (EH) during stable antihypertensive therapy. F-Rmin, ACR on three non-consecutive morning urine samples, pulse wave velocity (PWV), and 24-h ambulatory blood pressure (ABPM) were measured. Results ACR was low (0.39 and 0.30-0.60), but abnormal small artery structure defined as F-Rmin > mean + 2 standard deviations of normotensive value (1.99 + 1 mmHg min/(ml/100 ml)) was present in 45% (n = 30). The mean F-Rmin was 2.89 ± 0.09 mmHg min/(ml/100 ml). ACR correlated significantly to PWV (r(2 )=( )0.11; p < 0.05) and pulse pressure (r(2 )=( )0.15; p < 0.001), but not F-Rmin and (r(2 )=( )0.05, p = 0.07). Conclusions Abnormal microvascular structure was present even in EH patients with low UAE. ACR correlated to arterial stiffness and not to small artery structure; therefore, UEA did not reflect microvascular damage in this population. ACR and F-Rmin thus reflect two distinct types of subclinical organ damage in hypertension.

Aortic Calcification is Associated With the Difference Between Invasive Central and Cuff-Measured Brachial Blood Pressure in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with accelerated vascular calcification and increased central systolic blood pressure when measured invasively (invCSBP) relative to cuff-based brachial systolic blood pressure (cuffSBP). The contribution of aortic wall calcification to this phenomenon has not been clarified. We, therefore, examined the effects of aortic calcification on cuffSBP and invCSBP in a cohort of patients representing all stages of CKD. METHODS: During elective coronary angiography, invCSBP was measured in the ascending aorta with a fluid-filled catheter with simultaneous recording of cuffSBP using an oscillometric device. Furthermore, participants underwent a non-contrast computed tomography scan of the entire aorta with observer-blinded calcification scoring of the aortic wall ad modum Agatston. RESULTS: We included 168 patients (mean age 67.0 ±â€…10.5, 38 females) of whom 38 had normal kidney function, while 30, 40, 28, and 32 had CKD stages 3a, 3b, 4, and 5, respectively. Agatston scores adjusted for body surface area ranged from 48 to 40,165. We found that invCSBP increased 3.6 (95% confidence interval 1.4-5.7) mm Hg relative to cuffSBP for every 10,000-increment in aortic Agatston score. This association remained significant after adjustment for age, diabetes, antihypertensive treatment, smoking, eGFR, and BP level. No such association was found for diastolic BP. CONCLUSIONS: Patients with advanced aortic calcification have relatively higher invCSBP for the same cuffSBP as compared to patients with less calcification. Advanced aortic calcification in CKD may therefore result in hidden central hypertension despite apparently well-controlled cuffSBP. ClinicalTrials.gov identifier: NCT04114695.

Obstructive sleep apnea, coronary calcification and arterial stiffness in patients with diabetic kidney disease.

BACKGROUND AND AIMS: Obstructive sleep apnea (OSA) may accelerate arterial calcification, but the relation remains unexplored in diabetic kidney disease (DKD). We examined the associations between OSA, coronary calcification and large artery stiffness in patients with DKD and reduced renal function. METHODS: Patients with type 2 diabetes, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and urine albumin-creatinine ratio (UACR) > 30 mg/g were tested for OSA quantified by the apnea-hypopnea index (AHI, events/hour). Patients without OSA (AHI< 5) were compared to patients with moderate (AHI 15-29) or severe (AHI ≥30) OSA and underwent computed tomography angiography with coronary Agatston scoring (CAS) to quantify coronary calcification. Arterial stiffness was determined as carotid-femoral pulse wave velocity (PWV). RESULTS: Among 114 patients with acceptable AHI recordings had 43 no OSA, 33 mild OSA and 38 moderate-severe OSA. Mean age of the 74 patients completing the study was 71.5 ± 9.4 years (73% males), eGFR 32.2 ± 12.3 ml/min/1.73 m2 and UACR 533 (192-1707) mg/g. CAS (ln-transformed) was significantly higher in patients with OSA compared to patients without (6.6 ± 1.7 vs. 5.6 ± 2.4, p = 0.04), and the same was observed for PWV (11.9 ± 2.7 vs. 10.5 ± 2.2 m/s, p = 0.02). In multivariable linear regression analyses adjusted for sex, age, body mass index, UACR, and mean arterial pressure, moderate-severe OSA remained significantly associated with PWV but not with CAS. Dominance analysis revealed OSA as the third and second most important factor relative to CAS and PWV respectively. CONCLUSIONS: In DKD patients, moderate-severe OSA is a significant predictor of arterial stiffness but is not independently associated with coronary calcification.

Effect of alfacalcidol on cardiac function in patients with chronic kidney disease stage 4 and secondary hyperparathyroidism: a pilot study.

OBJECTIVE: Left ventricular hypertrophy (LVH) is highly prevalent in chronic kidney disease (CKD) and a risk marker for cardiovascular mortality. It was hypothesized that vitamin D deficiency could play an important role in the pathogenesis of left ventricular hypertrophy and dysfunction in CKD. An open-labelled randomized study was performed comparing the effect of alfacalcidol versus no treatment in patients with CKD 4, secondary hyperparathyroidism and LVH. The primary endpoint was regression of LVH. Secondary endpoints were changes in left ventricular function. MATERIAL AND METHODS: Twenty-four patients were screened. Of these, 14 had LVH according to the criteria used. Six were randomized to alfacalcidol and seven to no treatment. The patient follow-up was 6 months. Left ventricular mass and function were measured by echocardiography. RESULTS: Parathyroid hormone decreased by 72% and -3% in the alfacalcidol-treated and non-treated groups, respectively (p < 0.05), while serum Ca(2+) increased by 9% and -1.6%, respectively (p < 0.05), and serum phosphate was unchanged. The left ventricular mass index was unchanged, whereas fractional shortening (20% vs 2%, p < 0.005) and Tei index (36% vs 12%, p < 0.05) increased significantly. Systolic and diastolic blood pressure was unchanged. CONCLUSION: Short-term treatment with alfacalcidol did not induce regression of LVH; however, left ventricular function became hyperdynamic but less effective in patients with CKD. This could be problematic in the long term.

Renal Artery Stenting in Consecutive High-Risk Patients With Atherosclerotic Renovascular Disease: A Prospective 2-Center Cohort Study.

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0-170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8-7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m2 (95% CI, 36.6-45.6). In 96 patients with available 3-month follow-up data, mean 24-hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4-23.8; P<0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%-62%; P<0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m2 (95% CI, 4.5-11.1; P<0.001). All changes persisted after 24 month follow-up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov. Identifier: NCT02770066.

Effects of enhanced versus reduced vasodilating treatment on brachial and central blood pressure in patients with chronic kidney disease: a randomized controlled trial.

BACKGROUND: Blood pressure (BP) control is important in chronic kidney disease (CKD), but a reduction in brachial BP may not mirror changes in central aortic BP (cBP) during antihypertensive medication. We hypothesize that a fall in cBP is better reflected during enhanced vasodilation treatment (EVT) compared with reduced vasodilation treatment (RVT) because of different hemodynamic actions of these interventions. METHODS: Eighty-one hypertensive CKD stage 3-4 patients (mean measured glomerular filtration rate 36 ml/min per 1.73 m2) were randomized to either EVT based on renin--angiotensin blockade and/or amlodipine or RVT based on nonvasodilating ß-blockade (metoprolol). Before randomization and following 18 months of treatment, we performed 24-h ambulatory BP measurements (ABPM) and radial artery pulse wave analysis for estimation of cBP and augmentation index (AIx). Forearm resistance (Rrest) was determined by venous occlusion plethysmography and arterial stiffness by carotid--femoral pulse wave velocity (PWV). Matched healthy controls were studied once for comparison. RESULTS: Compared with controls, CKD patients had elevated ABPM, cBP and PWV. Although ABPM remained unchanged from baseline to follow-up in both treatment groups, cBP decreased 4.7/2.9 mmHg (systolic/diastolic) during EVT and increased 5.1/1.5 mmHg during RVT (Δ=9.8/4.4 mmHg, P=0.02 for SBP, P = 0.05 for DBP). At follow-up, the difference between systolic cBP and 24-h ABPM (ΔBPsyst) was negatively associated with heart rate and positively associated with AIx and Rrest (all P < 0.01) but not PWV (P = 0.32). CONCLUSION: In CKD patients, EVT and RVT have opposite effects on cBP and the difference between cBP and ambulatory BP is larger for EVT than RVT.

Prognostic value of suPAR and hs-CRP on cardiovascular disease.

BACKGROUND AND AIMS: Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score. METHODS: A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models. RESULTS: 1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01-1.34) and 1.04 (95% CI 1.01-1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45-2.84) and 60-year-old subjects (1.44; 95% CI 1.09-1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32). CONCLUSIONS: Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.

[Blood pressure measurement as performed in outpatient clinics is inexpedient].

Traditional office blood pressure (OBP) measurement as performed in busy outpatient clinics agrees poorly with awake ambulatory BP, and generally BP is severely overestimated. Especially elderly patients may be overtreated with the risk of symptomatic hypotension and fall injuries. Furthermore, truly high OBP measurements are often ignored as white coat hypertension, which leads to undertreatment of hypertension in high-risk individuals. Traditional OBP is thus of limited use and may even be harmful. Better methods are available and should be implemented.

Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartan on Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIR Study).

BACKGROUND AND AIM: Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan. DESIGN: Randomized, double-blind, placebo-controlled, one-year intervention trial. SETTING AND PARTICIPANTS: Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year. INTERVENTION: Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients. OUTCOMES AND MEASUREMENTS: Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension. RESULTS: At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters. CONCLUSION: Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen. TRIAL REGISTRATION: Clinicaltrials.gov NCT00791830.

Recent and long-term occupational noise exposure and salivary cortisol level.

Environmental and occupational noise exposure have been related to increased risk of cardiovascular disease, hypothetically mediated by stress-activation of the hypothalamic-pituitary-adrenal (HPA) axis. The objective of this study was to investigate the relation between recent and long-term occupational noise exposure and cortisol level measured off work to assess a possible sustained HPA-axis effect. We included 501 industrial, finance, and service workers who were followed for 24h during work, leisure, and sleep. Ambient occupational noise exposure levels were recorded every 5s by personal dosimeters and we calculated the full-shift LAEq value and estimated duration and cumulative exposure based on their work histories since 1980. For 332 workers who kept a log-book on the use of hearing protection devices (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the noise level at the ear. Salivary cortisol concentration was measured at 20.00 h, the following day at awakening, and 30 min after awakening on average 5, 14 and 14.5h after finishing work. The mean ambient noise exposure level was 79.9 dB(A) [range: 55.0-98.9] and the mean estimated level at the ear 77.7 dB(A) [range: 55.0-94.2]. In linear and mixed regression models that adjusted for age, sex, current smoking, heavy alcohol consumption, personal income, BMI, leisure-time noise exposure level, time since occupational noise exposure ceased, awakening time, and time of saliva sampling, we observed no statistically significant exposure response relation between recent, or long-term ambient occupational noise exposure level and any cortisol parameter off work. This was neither the case for recent noise level at the ear. To conclude, neither recent nor long-term occupational noise exposure levels were associated with increased cortisol level off work. Thus, our results do not indicate that a sustained activation of the HPA axis, as measured by cortisol, is involved in the causal pathway between occupational noise exposure and cardiovascular disease.

Renal and cardiovascular effects of irbesartan in dialysis patients--a randomized controlled trial protocol (SAFIR study).

INTRODUCTION: Cardiovascular (CV) events are a major cause of morbidity and mortality in haemodialysis (HD) patients. Hypertension, increased arterial stiffness and left ventricular (LV) hypertrophy are highly prevalent and are often poorly controlled. Volume overload is an important factor and survival could be improved by treatment strategies that preserve residual renal function (RRF), reduce blood pressure, and decrease arterial stiffness and LV hypertrophy. Angiotensin II receptor blocker (ARB) treatment can prevent CV events in patients with hypertension and heart failure. However, few data exist in patients with chronic renal failure and it is not known whether ARB treatment improves clinical outcome in HD patients. MATERIAL AND METHODS: This is a randomized, controlled and double-blinded intervention study. A total of 82 HD patients from six Danish HD centres will be treated for a year with an ARB (irbesartan) or placebo. The inclusion criteria are urine output > 300 ml/day, dialysis vintage < 1 year and LV ejection fraction > 30%. The primary outcomes are change in RRF, LV hypertrophy, arterial stiffness and intra-dialytic haemodynamics. CONCLUSION: If ARB-treatment improves RRF and intermediate CV endpoints in a group of newly started HD patients, it may improve the survival for this high risk population. FUNDING: The trial is investigator-initiated, investigator-driven and supported by the Danish Agency for Science, Technology and Innovation and several private foundations.

Hospital-based versus community-based shared care cardiac rehabilitation after acute coronary syndrome: protocol for a randomized clinical trial.

INTRODUCTION: Participation in cardiac rehabilitation (CR) is poor although CR reduces morbidity and mortality. One way in which attendance may potentially be improved is by involving municipal health-care centres (MHCC) and the patient's general practitioner (GP) to a larger degree in a model of shared care cardiac rehabilitation (SC-CR). Our study tests the feasibility of SC-CR and compares the attendance and effects of SC-CR with the individually tailored hospital-based CR (H-CR) programme. MATERIAL AND METHODS: After admission for acute coronary syndrome (ACS) patients are randomized to phase II CR which is conducted either as SC-CR or H-CR. During SC-CR the patient is seen once in-hospital after which the GP takes over. MHCC supports the GP by offering educational intervention regarding smoking cessation, exercise, nutrition and mental health. A total of 208 persons hospitalised due to acute coronary syndrome are to be randomized before hospital discharge. CONCLUSION: The study aims to examine whether the organisation of SC-CR is feasible and provides the expected benefits. FUNDING: The trial is funded by Region Central Denmark. TRIAL REGISTRATION: Clinical Trials ID: NTC 01522001.

Catheter-based renal denervation for treatment of resistant hypertension.

INTRODUCTION: Activation of renal sympathetic nerves is associated with the development of hypertension. Catheter-based renal sympathetic denervation with radiofrequency energy ablation is a new promising treatment option for resistant hypertension. We here report the first Danish experiences and results with this technique. MATERIAL AND METHODS: Nine patients with resistant hypertension and a day-time 24-hour ambulatory blood pressure (BP) of 152/89 mmHg ± 10/10 (standard deviation) mmHg despite treatment with 5.4 ± 1.4 anti-hypertensive drugs underwent catheter-based renal sympathetic denervation with the Symplicity catheter. RESULTS: No periprocedural complications or adverse events during follow-up were observed. Seven patients received complete ablation and two patients only partial ablation. Five patients responded to the treatment with a reduction in day-time 24-hour ambulatory BP from 158/94 ± 13/9 mmHg to 139/82 ± 10/8 mmHg (p < 0.05) at the one month follow-up and a reduction in the number of anti-hypertensive drugs from 5.4 ± 1.6 to 3.4 ± 0.9 (p < 0.05). BP in the remaining four patients was not significantly changed and antihypertensive therapy was not changed. CONCLUSION: Catheter-based renal sympathetic denervation is a feasible and in several cases also effective treatment option for patients with resistant hypertension. Adequately designed controlled trials are needed to assess the long-term safety and the full potential of this treatment.

Disproportionally impaired microvascular structure in essential hypertension.

BACKGROUND: Increased microvascular resistance and small artery remodelling are key abnormalities in the pathophysiology of essential hypertension. We investigated the relation between the impairment of coronary and forearm minimum vascular resistances (C-Rmin and F-Rmin) and the degree of hypertension. METHOD: Seventy-five never-treated essential hypertension patients with 24-h systolic blood pressure (BP) at least 130 mmHg or diastolic BP at least 80 mmHg were assigned into grade 1 (office BP 140/90-159/99 mmHg) and grade 2 (office BP 160/100-179/109 mmHg) hypertension and compared to normotensive controls (n = 25). The patients were (48 years, 60% men) without cardiovascular disease. C-Rmin and coronary flow reserve (CFR) were derived from flow measurements in the left anterior descending artery using transthoracic echocardiography. F-Rmin was measured using venous occlusion plethysmography. Resting systemic vascular resistance index (SVRI) was measured with a gas rebreathing technique. RESULTS: Compared to normotensive controls: 24-h mean BP was raised 14% in grade 1 essential hypertension and 28% in grade 2 essential hypertension, whereas F-Rmin and C-Rmin were elevated by 58 and 87% in grade 1 essential hypertension and 72 and 125% in grade 2 essential hypertension. C-Rmin and F-Rmin were thus both increased more than expected from the BP level. SVRI and left-ventricular mass were increased proportionally to the BP. CFR was decreased by approximately 30% in both essential hypertension groups. CONCLUSION: The results demonstrate excessive microvascular structural abnormalities in hypertension suggesting microvascular alterations occur early and not just as an adaptation to the BP level. Thus the level of BP elevation does not give an accurate indication of the microvascular involvement and impairment in essential hypertension.