Influence of intensive lipid-lowering on CT derived fractional flow reserve in patients with stable chest pain: Rationale and design of the FLOWPROMOTE study.

INTRODUCTION: Coronary CT angiography (CTA) derived fractional flow reserve (FFRCT ) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated. AIM: To test whether lipid lowering therapy is associated with significant improvement in FFRCT , and whether there is a dose-response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery. METHODS: Investigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first-line CTA, and FFRCT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFRCT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18-month difference in FFRCT using (1) the FFRCT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study. CONCLUSION: The results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.

Coronary CT angiography derived FFR in patients with left main disease.

The presence of left main coronary artery disease (LMCAD) is associated with an unfavorable clinical outcome. The clinical utility of FFRCT testing for non-invasive physiological assessment in LMCAD remains largely unknown. In this single center observational study LMCAD patients were retrospectively identified between November 2015 and December 2017. We evaluated the relationship between LMCAD diameter stenosis and downstream FFRCT values, and the clinical consequences following FFRCT testing in patients with LMCAD. The composite endpoint (all-cause death, myocardial infarction, unplanned revascularization) was determined over a median follow-up of 1.1 years. LMCAD was registered in 432 of 3202 (13%) patients having coronary CTA. FFRCT was prescribed in 213 (49%), while 59 (14%) patients were referred directly to invasive angiography or myocardial perfusion imaging. FFRCT was performed in 195 (45%) patients. LM stenosis severity was inversely related to downstream FFRCT values. In patients with simple LMCAD with stenosis ≥ 50%, > 80% had FFRCT > 0.80 in non-diseased proximal and downstream segments (n = 7). No patients with simple LMCAD and FFRCT > 0.80 (n = 20) suffered an adverse clinical outcome. FFRCT testing in patients with LMCAD is feasible. LM stenosis severity is inversely related to FFRCT value. Patients with LMCAD and FFRCT > 0.80 have favorable clinical outcomes at short-term follow-up. Large-scale studies assessing the clinical utility and safety of deferring invasive catheterization following FFRCT testing in patients with LMCAD are warranted.

Clinical outcomes following real-world computed tomography angiography-derived fractional flow reserve testing in chronic coronary syndrome patients with calcification.

AIMS: This study sought to investigate outcomes following a normal CT-derived fractional flow reserve (FFRCT) result in patients with moderate stenosis and coronary artery calcification, and to describe the relationship between the extent of calcification, stenosis, and FFRCT. METHODS AND RESULTS: Data from 975 consecutive patients suspected of chronic coronary syndrome with stenosis (30-70%) determined by computed CT angiography and FFRCT to guide downstream management decisions were reviewed. Median (range) follow-up time was 2.2 (0.5-4.2) years. Coronary artery calcium (CAC) scores were ≥400 in 25%, stenosis ≥50% in 83%, and FFRCT >0.80 in 51% of the patients. There was a lower incidence of the composite endpoint (death, myocardial infarction, hospitalization for unstable angina, and unplanned coronary revascularization) at 4.2 years in patients with any CAC and FFRCT > 0.80 vs. FFRCT ≤ 0.80 (3.9% and 8.7%, P = 0.04), however, in patients with CAC scores ≥400 the risk difference between groups did not reach statistical significance, 4.2% vs. 9.7% (P = 0.24). A negative relationship between CAC scores and FFRCT irrespective of stenosis severity was demonstrated. CONCLUSION: FFRCT shows promise in identifying patients with stenosis and calcification who can be managed without further downstream testing. Moreover, an inverse relationship between CAC levels and FFRCT was demonstrated. Studies are needed to further assess the clinical utility of FFRCT in patients with extensive coronary calcification.

Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).

Coronary CT Angiographic and Flow Reserve-Guided Management of Patients With Stable Ischemic Heart Disease.

BACKGROUND: Clinical outcomes following coronary computed tomography-derived fractional flow reserve (FFRCT) testing in clinical practice are unknown. OBJECTIVES: This study sought to assess real-world clinical outcomes following a diagnostic strategy including first-line coronary computed tomography angiography (CTA) with selective FFRCT testing. METHODS: The study reviewed the results of 3,674 consecutive patients with stable chest pain evaluated with CTA and FFRCT testing to guide downstream management in patients with intermediate stenosis (30% to 70%). The composite endpoint (all-cause death, myocardial infarction, hospitalization for unstable angina, and unplanned revascularization) was determined in 4 patient groups: 1) CTA stenosis <30%, optimal medical treatment (OMT), and no additional testing; 2) FFRCT >0.80, OMT, no additional testing; 3) FFRCT ≤0.80, OMT, no additional testing; and 4) FFRCT ≤0.80, OMT, and referral to invasive coronary angiography. Patients were followed for a median of 24 (range 8 to 41) months. RESULTS: FFRCT was available in 677 patients, and the test result was negative (>0.80) in 410 (61%) patients. In 75% of the patients with FFRCT >0.80, maximum coronary stenosis was ≥50%. The cumulative incidence proportion (95% confidence interval [CI]) of the composite endpoint at the end of follow-up was comparable in groups 1 (2.8%; 95% CI: 1.4% to 4.9%) and 2 (3.9%; 95% CI: 2.0% to 6.9%) (p = 0.58) but was higher (when compared with group 1) in groups 3 (9.4%; p = 0.04) and 4 (6.6%; p = 0.08). Risk of myocardial infarction was lower in group 4 (1.3%) than in group 3 (8%; p < 0.001). CONCLUSIONS: In patients with intermediate-range coronary stenosis, FFRCT is effective in differentiating patients who do not require further diagnostic testing or intervention (FFRCT >0.80) from higher-risk patients (FFRCT ≤0.80) in whom further testing with invasive coronary angiography and possibly intervention may be needed. Further studies assessing the risk and optimal management strategy in patients undergoing first-line CTA with selective FFRCT testing are needed.

Effects of renal denervation on coronary flow reserve and forearm dilation capacity in patients with treatment-resistant hypertension. A randomized, double-blinded, sham-controlled clinical trial.

BACKGROUND: Microvascular impairment is well documented in hypertension. We investigated the effect of renal sympathetic denervation (RDN) on cardiac and peripheral microvasculature in patients with treatment-resistant essential hypertension (TRH). METHODS: A randomized, single centre, double-blinded, sham-controlled clinical trial. Fifty-eight patients with TRH (ambulatory systolic BP (ASBP) ≥ 145mmHg) despite stable treatment were randomized to RDN or SHAM. RDN was performed with the unipolar Medtronic Flex catheter. Coronary flow reserve (CFR) and coronary- and forearm minimum vascular resistance (C-Rmin and F-Rmin) were determined using transthoracic Doppler echocardiography and F-Rmin with venous occlusion plethysmography at baseline and at six-months follow-up. RESULTS: RDN was performed with 5.3±0.2 lesions in the right renal artery and 5.4±0.2 lesions in the left. Baseline ASBP was 152±2mmHg (RDN, n=29) and 154±2mmHg (SHAM, n=29). Similar reductions in MAP were seen at follow up (-3.5±2.0 vs. -3.2±1.8, P=0.92). Baseline CFR was 2.9±0.1 (RDN) and 2.4±0.1 (SHAM), with no significant change at follow-up (0.2±0.2 vs. -0.1±0.2, P=0.57). C-Rmin was 1.9±0.3 (RDN) and 2.7±0.6 (SHAM) (mmHgmin/ml pr. 100g) and did not change significantly (0.3±0.5 vs. -0.4±0.8, P=0.48). F-Rmin was 3.6±0.2 (RDN) and 3.6±0.3 (SHAM) (mmHgmin/ml pr. 100ml tissue) and unchanged at follow-up (4.2±0.4 vs. 3.8±0.2, P=0.17). Left ventricular mass index was unchanged following RDN (-4±7 (RDN) vs. 3±5 (SHAM) (g/m2) P=0.38). CONCLUSION: The current study does not support positive effects of RDN on microvascular impairment in TRH.

Effects of Renal Denervation on Insulin Sensitivity and Inflammatory Markers in Nondiabetic Patients with Treatment-Resistant Hypertension.

Increased sympathetic activity is important in the pathogenesis of hypertension and insulin resistance. Afferent signaling from the kidneys elevates the central sympathetic drive. We investigated the effect of catheter-based renal sympathetic denervation (RDN) on glucose metabolism, inflammatory markers, and blood pressure in nondiabetic patients with treatment-resistant hypertension. Eight subjects were included in an open-labelled study. Each patient was studied before and 6 months after RDN. Endogenous glucose production was assessed by a 3-3H glucose tracer, insulin sensitivity was examined by hyperinsulinemic euglycemic clamp, hormones and inflammatory markers were analyzed, and blood pressure was measured by office blood pressure readings and 24-hour ambulatory blood pressure monitoring. Insulin sensitivity (M-value) increased nonsignificantly from 2.68 ± 0.28 to 3.07 ± 0.41 (p = 0.12). A significant inverse correlation between the increase in M-value and BMI 6 months after RDN (p = 0.03) was found, suggesting beneficial effects on leaner subjects. Blood pressure decreased significantly, but there were no changes in hormones, inflammatory markers, or endogenous glucose production. Our results indicate that RDN may improve insulin sensitivity in some patients with treatment-resistant hypertension, albeit confirmation of these indications of beneficial effects on leaner subjects awaits the outcome of larger randomized controlled studies.

Myocardial Perfusion Imaging Versus Computed Tomography Angiography-Derived Fractional Flow Reserve Testing in Stable Patients With Intermediate-Range Coronary Lesions: Influence on Downstream Diagnostic Workflows and Invasive Angiography Findings.

BACKGROUND: Data on the clinical utility of coronary computed tomography angiography-derived fractional flow reserve (FFRCT) are sparse. In patients with intermediate (40-70%) coronary stenosis determined by coronary computed tomography angiography, we investigated the association of replacing standard myocardial perfusion imaging with FFRCT testing with downstream utilization of invasive coronary angiography (ICA) and the diagnostic yield of ICA (rate of no obstructive disease, and rate of revascularization). METHODS AND RESULTS: This was a single-center observational study of symptomatic patients with suspected coronary artery disease referred to coronary computed tomography angiography between 2013 and 2015. Patients were divided into 3 historical groups based on the adjunctive functional testing approach: myocardial perfusion imaging (n=1332) or FFRCT "implementation" (n=800) or "clinical use" (n=1391). Propensity score matching was used to estimate the average period effect on outcomes. Patients in the FFRCT clinical use group versus the myocardial perfusion imaging group were older and had higher pretest probability of obstructive disease. After adjusting for baseline risk characteristics, there was a reduction in downstream ICA utilization (absolute risk difference: -4.2; 95% CI, -6.9 to -1.6; P=0.002). In patients referred to ICA, findings of no obstructive coronary artery disease decreased (-12.8%; 95% CI, -22.2 to -3.4; P=0.008) and rate of coronary revascularization increased (14.1%; 95% CI, 3.3-24.9; P=0.01), as did availability of functional information for guidance of revascularization (27.8%; 95% CI, 11.3-44.4; P<0.001) after clinical adoption of FFRCT. CONCLUSIONS: Replacing adjunctive myocardial perfusion imaging with FFRCT testing for functional assessment of intermediate stenosis determined by coronary computed tomography angiography in stable coronary artery disease was associated with less ICA utilization, and a higher ICA diagnostic yield. The findings in this observational study needs confirmation in prospective, randomized trials.

Clinical Use of Coronary CTA-Derived FFR for Decision-Making in Stable CAD.

OBJECTIVES: The goal of this study was to assess the real-world clinical utility of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) for decision-making in patients with stable coronary artery disease (CAD). BACKGROUND: FFRCT has shown promising results in identifying lesion-specific ischemia. The real-world feasibility and influence on the diagnostic work-up of FFRCT testing in patients suspected of having CAD are unknown. METHODS: We reviewed the complete diagnostic work-up of nonemergent patients referred for coronary computed tomography angiography over a 12-month period at Aarhus University Hospital, Denmark, including all patients with new-onset chest pain with no known CAD and with intermediate-range coronary lesions (lumen reduction, 30% to 70%) referred for FFRCT. The study evaluated the consequences on downstream diagnostic testing, the agreement between FFRCT and invasively measured FFR or instantaneous wave-free ratio (iFR), and the short-term clinical outcome after FFRCT testing. RESULTS: Among 1,248 patients referred for computed tomography angiography, 189 patients (mean age 59 years; 59% male) were referred for FFRCT, with a conclusive FFRCT result obtained in 185 (98%). FFRCT was ≤0.80 in 31% of patients and 10% of vessels. After FFRCT testing, invasive angiography was performed in 29%, with FFR measured in 19% and iFR in 1% of patients (with a tendency toward declining FFR-iFR guidance during the study period). FFRCT ≤0.80 correctly classified 73% (27 of 37) of patients and 70% (37 of 53) of vessels using FFR ≤0.80 or iFR ≤0.90 as the reference standard. In patients with FFRCT >0.80 being deferred from invasive coronary angiography, no adverse cardiac events occurred during a median follow-up period of 12 (range 6 to 18 months) months. CONCLUSIONS: FFRCT testing is feasible in real-world symptomatic patients with intermediate-range stenosis determined by coronary computed tomography angiography. Implementation of FFRCT for clinical decision-making may influence the downstream diagnostic workflow of patients. Patients with an FFRCT value >0.80 being deferred from invasive coronary angiography have a favorable short-term prognosis.

Transcatheter Aortic Valve Thrombosis: Incidence, Predisposing Factors, and Clinical Implications.

BACKGROUND: There are limited data on the incidence, clinical implications, and predisposing factors of transcatheter heart valve (THV) thrombosis following transcatheter aortic valve replacement (TAVR). OBJECTIVES: The authors assessed the incidence, potential predictors, and clinical implications of THV thrombosis as determined by contrast-enhanced multidetector computed tomography (MDCT) after TAVR. METHODS: Among 460 consecutive patients who underwent TAVR with the Edwards Sapien XT or Sapien 3 (Edwards Lifesciences, Irvine, California) THV, 405 (88%) underwent MDCT in addition to transthoracic and transesophageal echocardiography 1 to 3 months post-TAVR. MDCT scans were evaluated for hypoattenuated leaflet thickening that indicated THV thrombosis. RESULTS: MDCT verified THV thrombosis in 28 of 405 (7%) patients. A total of 23 patients had subclinical THV thrombosis, whereas 5 (18%) patients experienced clinically overt obstructive THV thrombosis. THV thrombosis risk did not differ among different generations of THVs (8% vs. 6%; p = 0.42). The risk of THV thrombosis in patients who did not receive warfarin was higher compared with patients who received warfarin (10.7% vs. 1.8%; risk ratio [RR]: 6.09; 95% confidence interval [CI]: 1.86 to 19.84). A larger THV was associated with an increased risk of THV thrombosis (p = 0.03). In multivariable analysis, a 29-mm THV (RR: 2.89; 95% CI: 1.44 to 5.80) and no post-TAVR warfarin treatment (RR: 5.46; 95% CI: 1.68 to 17.7) independently predicted THV thrombosis. Treatment with warfarin effectively reverted THV thrombosis and normalized THV function in 85% of patients as documented by follow-up transesophageal echocardiography and MDCT. CONCLUSIONS: Incidence of THV thrombosis in this large study was 7%. A larger THV size may predispose to THV thrombosis, whereas treatment with warfarin appears to have a protective effect. Although often subclinical, THV thrombosis may have important clinical implications.

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 ±â€Š12 mmHg (RDN) and 159 ±â€Š14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ±â€Š18.8 mmHg (RDN) vs. -6.0 ±â€Š13.5 mmHg (SHAM)] and at 6 months [-6.1 ±â€Š18.9 mmHg (RDN) vs. -4.3 ±â€Š15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ±â€Š2.7 (RDN) vs. 7.0 ±â€Š2.5 (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.

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.

Changes in blood pressure and systemic vascular resistance do not predict microvascular structure during treatment of mild essential hypertension.

BACKGROUND: Essential hypertension is characterized by small artery remodeling and increased systemic vascular resistance (SVR). We hypothesized that changes in SVR index (SVRI) were associated with measures of small artery structure as reflected by minimum coronary and forearm vascular resistance (C-Rmin and F-Rmin, respectively). Also, we investigated how F-Rmin is related to C-Rmin, coronary flow reserve (CFR), left ventricular mass index (LVMI) and blood pressure (BP). METHOD: Sixty-six never-treated patients with uncomplicated mild essential hypertension had the following measured at baseline: 24-h blood BP, LVMI, CFR and C-Rmin (echocardiography), F-Rmin (forearm plethysmography) and SVRI determined by a gas re-breathing method. After 6 months of antihypertensive therapy administered by the general practitioner, the patients returned for follow-up measurements. RESULTS: Changes in SVRI did not correlate to changes in F-Rmin (r = 0.001, P = 0.98) or C-Rmin (r = 0.13, P = 0.39) but did correlate to changes in CFR (r = 0.30, P = 0.04). Further analysis was performed by assigning the patients into two groups according to the median of drop in F-Rmin. When adjusted in a multivariate model, changes in F-Rmin (-8.1 ±â€Š3.2%) were significantly associated with changes in C-Rmin (-9.3 ±â€Š4.9%) and LVMI (-6.9 ±â€Š1.7%) (P < 0.01), but not to either 24-h BP, SVRI or CFR. CONCLUSION: The results show that changes in neither BP nor SVRI reflected changes in minimum vascular resistance. However, changes in the forearm and coronary microcirculation occurred in parallel. Moreover, we demonstrated that neither BP nor SVRI reduction can predict changes in microvascular structure in hypertension. Thus, direct measurements of microvascular structure are needed to determine whether improvement is obtained.

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 >or= 0.083 (mean level of the hypertensive cohort), RR = 2.34 [95% confidence interval (CI) 1.11-4.95], and with M: L >or= 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 adapts to vasodilatation rather than to blood pressure during antihypertensive treatment.

OBJECTIVE: Correction of the abnormal structure of resistance arteries in essential hypertension may be an important treatment goal in addition to blood pressure (BP) reduction. We investigated how this may be achieved in a prospective clinical study. METHODS: Plethysmography was used to measure forearm resting vascular resistance (Rrest) and minimum vascular resistance (Rmin) as a measure of vascular structure. Two different groups of patients with essential hypertension were examined at baseline and after 6 months of antihypertensive treatment. In group A, 21 patients with never-treated essential hypertension were treated by their general practitioners using a variety of drugs to allow an assessment of the drug-independent effects. In group B, 28 beta-blocker-treated patients were shifted to angiotensin II receptor blocker treatment (eprosartan) to allow vasodilatation with no change in BP. RESULTS: In group A, mean ambulatory blood pressure (ABP) fell from 119 +/- 2 (SE) to 103 +/- 2 mmHg (P < 0.01), whereas mean ABP was unchanged in group B (100 +/- 1 to 99 +/- 1 mmHg, P = NS). Both groups showed similar reductions in Rrest (-33.4 and -28.5%, respectively) and in Rmin (-15.4 and -15.6%, respectively). There was a strong correlation between changes in Rrest and Rmin within both groups (r = 0.57, P < 0.01 and r = 0.68, P < 0.0001, respectively), whereas the change in BP in group A was not correlated to the change in Rmin (r = -0.03). CONCLUSION: The correction of forearm resistance artery structure during antihypertensive treatment depends on the vasodilatation achieved rather than BP reduction.