Minimal Vascular Resistance Research Articles

Insulin resistance is associated to future hypertension in normotensive salt-sensitive individuals: a 10-year follow-up study.

Salt-sensitive hypertension is associated with insulin resistance in nonobese individuals. However, no data have been reported for normotensive offspring of hypertensive salt-sensitive parents. To evaluate in normotensive salt-sensitive or salt-resistant offspring of hypertensive parents (offSS-HT and offSR-HT, respectively): the possible association between insulin resistance and endothelial dysfunction, and the risk of developing hypertension in a 10-year follow-up. Forty-one offSS-HT (29 ± 2 years; 20 female) and 36 offSR-HT (25 ± 3 years; 16 female) were followed up for 10 years. Both groups were considered lean. At baseline, creatinine clearance (CrCl), 24 h urinary albumin excretion (UAE), glycemia, and insulinemia were measured before and after 60 and 120 min of glucose overload (75 g). HOMA Index and the area under the curve (AUC) were calculated. Blood pressure (BP) and 24 h urine sodium excretion was measured annually. Postischemic minimum vascular resistance (forearm plethysmography) was assessed at baseline. In offSS-HT, UAE (53 ± 3 mg/min) and CrCl (136 ± 8 ml/min) were higher in offSS-HT than in offSR-HT. (UAE: 12 ± 4 mg.min; p,0.01 and CrCl 107 ± 6 ml.min; P < 0.01). An impaired vasodilatory postischemic response was observed in offSS-HT compared with offSR-HT ( P < 0.01). In offSS-HT glycemia, insulin, AUC at 69 and 120 min post OTG were greater than in offSR-HT, p < 0.02. In offSS-HT, blood pressure rose ( P < 0.01) the 10 years follow-up compared with offSR-HT. Salt sensitivity in the offspring of hypertensive salt-sensitive individuals is associated with insulin resistance and endothelial dysfunction and is prone to hypertension over a short period of time.

PS-C29-7: ASSOCIATION OF SERUM LEPTIN TO ADIPONECTIN RATIO AND CARDIOVASCULAR STRUCTURAL INDICES IN ESSENTIAL HYPERTENSIVE PATIENTS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Dysregulated leptin and adiponectin profile is known to be associated with atherosclerotic disease. The evaluation of the leptin to adiponectin (L/A) ratio has been suggested as a powerful useful atherosclerotic index compared with adiponectin and leptin alone in patients with type 2 diabetes and obesity. In this study, we investigated the usefulness of L/A ratio for vascular structural abnormalities in essential hypertensive patients. Design and method: In 151 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion (UAE) less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), blood sampling, 24-hour urine collection, and 24-hour blood pressure monitoring were performed. Intima-media thickness of carotid artery (IMT) and minimal forearm vascular resistance (MVR) (wall to lumen ratio in resistance vessel) were also measured by using ultrasonography and strain-gauge plethysmography, respectively. Results: L/A ratio was higher in men than in women (1.23 ± 1.56 vs 0.73 ± 0.87, p &lt; 0.05). There was no correlation between L/A ratio and systolic and diastolic blood pressure, and pulse rate. L/A ratio correlated positively with body mass index, triglyceride, hemoglobin A1c, HOMA-R and urinary C-peptide excretion (r = 0.57, 0.20, 0.20, 0.31, 0.27, p &lt; 0.05, respectively) and negatively with HDL-cholesterol (r = -0.24, p &lt; 0.05). In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively)In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively), whereas these indices did not associated with leptin and adiponectin individually. In multiple regression analysis, L/A ratio was an independent determinant for UAE, IMT and MVR. Conclusions: In patients with essential hypertension, L/A ratio was associated with obesity, abnormal glucose and lipid metabolism, increase in microalbuminuria, and arterial and arteriolar sclerosis. L/A ratio was considered as a useful indicator of vascular structural abnormalities in patients with essential hypertension.

INFLUENCE OF RENAL TRANSPLANTATION AND LIVING KIDNEY DONATION ON LARGE ARTERY STIFFNESS AND PERIPHERAL VASCULAR RESISTANCE

Objective: Living kidney donation (LKD) is possibly associated with an increased cardiovascular risk while on the other hand vascular health following renal transplantation may improve. The objective of our study was to assess alterations in intermediate vascular risk factors among living donors as well as their renal transplant recipients. Design and method: In a prospective study we measured glomerular filtration rate (GFR, 51Chrome EDTA clearance), 24-hour ambulatory blood pressure (BP), pulse wave velocity (PWV, Spygmocor), central augmentation index (AIx) and in addition also forearm resting and minimal vascular resistance (Rrest and Rmin respectively) using classic venous occlusion plethysmography. The study population consisted of living kidney donors (n = 58, 45 ± 13 years, 46% males) and their corresponding renal transplant recipients who were willing to participate in the study (n = 51, 50 ± 12 years, 76% males). The investigations were performed before and one year after donation or transplantation. Results: After kidney donation GFR decreased by 33% to 65 ± 11 ml/min/1.73m2 while the transplant recipients obtained a GFR of 55 ± 9 ml/min/1.73m2. Twentyfour-hour mean BP (MAP) remained unchanged in donors but decreased by 5 mmHg in recipients (P < 0.05) despite reduction in antihypertensive medication. Carotid-femoral PWV increased significantly by 0.3 m/s in donors (P < 0.05) but remained unchanged in the recipients. AIx was unaltered after kidney donation but decreased by 3.5% following transplantation (P < 0.01). Rrest increased significantly after kidney donation (P < 0.05) but was unaffected by transplantation, while no changes were noticed in Rmin in either of the groups. Changes in PWV were directly related to changes in 24-hour MAP in both groups while this was only the case for AIx in recipients. Multiple linear regression analysis (adjusting for age, gender and the baseline value of the studied parameter) did not detect independent effects of the achieved graft function on 24-hour MAP, PWV, AIx or vascular resistance at one-year follow-up. However, in donors a low post-donation GFR was related to higher AIx and Rrest. Conclusions: Renal transplantation reduced AIx without affecting PWV although changes in both parameters were related to changes in 24-hour MAP. Despite an unchanged BP level, living kidney donation resulted in increased PVW and Rrest.

Hypertension accelerates age-related intrarenal small artery (IRSA) remodelling and stiffness in rats with possible involvement of AGEs and RAGE.

To study changes in morphology, advanced glycation end products (AGEs) and the AGEs receptor, RAGE, that occur with ageing in intrarenal small arteries (IRSAs) of spontaneously hypertensive rats (SHRs) and to investigate the possible roles of hypertension, AGEs and RAGE in the progression of IRSA remodelling and stiffness with ageing in rats. Ageing SHRs and ageing normotensive Wistar Kyoto (WKY) rats were studied. The minimal renal vascular resistance (minRVR) was measured. Renal arcuate arteries (RAAs) and interlobular arteries (RILAs), the expression of α-smooth muscle actin, proliferating cell nuclear antigen, AGEs, RAGE and the plasma concentrations of AGEs were also examined. The IRSA minRVR, wall thickening, cell proliferation and collagen deposition in RILAs and RAAs gradually increased with age in SHRs and were much higher in 24-week-old SHRs than in age-matched WKY rats (p<0.05); these indexes in WKY rats were only elevated in the 72-week group (p<0.05). The expression of RAGE in the RAA and RILA tunica media in SHRs was upregulated by 24 weeks and 12 weeks (p<0.05), respectively, while AGEs levels in the plasma and in the IRSA tunica media were increased by 48 weeks (p<0.05) and increased gradually with age. The levels of both RAGE and AGEs in WKY rats were increased only at 72 weeks (p<0.05). Hypertension accelerates the development of age-related IRSA remodelling and stiffness in rats, which may be related to upregulation of RAGE in the IRSA tunica media and increased expression of AGEs at the late stage.

Arterial stiffness and peripheral vascular resistance in offspring of hypertensive parents: influence of sex and other confounders.

Established essential hypertension is associated with increased arterial stiffness and peripheral resistance, but the extent of vascular changes in persons genetically predisposed for essential hypertension is uncertain. Participants from the Danish Hypertension Prevention Project (DHyPP) (both parents hypertensive) (n = 95, 41 ± 1 years, 53% men) were compared with available spouses (n = 45, 41 ± 1 years) using measurements of ambulatory blood pressure (BP), left ventricular mass index (LVMI), pulse wave velocity, central BP and augmentation index (AIx) in addition to forearm resting and minimal resistance [forearm resting vascular resistance (Rrest) and forearm minimal vascular resistance (Rmin)]. DHyPP patients with participating spouses had higher 24-h mean BP (94 ± 1 vs. 88 ± 1 mmHg, P < 0.01), LVMI (94 ± 3 vs. 80 ± 2 g/m, P < 0.01), central SBP (121 ± 2 vs. 111 ± 2 mmHg, P < 0.01) and AIx (16.0 ± 1.2 vs. 10.5 ± 1.7%, P < 0.01), but similar carotid-femoral pulse wave velocity (7.5 ± 0.2 vs. 7.1 ± 0.2 m/s), Rrest (53 ± 3 vs. 51 ± 3 mmHg/ml/min/100 ml) and log Rmin (0.58 ± 0.02 vs. 0.55 ± 0.02 mmHg/ml/min/100 ml) when compared with spouses. Using multiple linear regression analysis (adjusting for sex, age, BMI, creatinine clearance and 24-h BP, heart rate and sodium excretion) AIx and LVMI remained elevated in DHyPP patients [4.2% (0.7; 7.7), P = 0.02 and 6.3 g/m (0.7; 11.9), P = 0.03]. For the entire DHyPP cohort AIx, Rrest and Rmin were higher in women than men (P < 0.01), and the same was true for AIx and Rmin among spouses (P < 0.05). Furthermore, AIx was linearly associated with Rrest and Rmin. Young to middle-aged individuals genetically predisposed for essential hypertension display increased AIx and LVMI, although vascular stiffness and peripheral resistance are still normal.

Evaluation of endothelial function by VOP and inflammatory biomarkers in patients with arterial hypertension.

Hypertension is associated with microcirculatory impairment. Our objectives were to evaluate endothelial function and inflammatory biomarkers in patients with resistant (RH) and mild to moderate (MMH) arterial hypertension in comparison to normotensives (control group-CG). Three groups, 25 patients each, have been investigated, by anamnesis, venous occlusion plethysmography (VOP) and serum determination of adhesion molecules (VCAM, ICAM), adiponectin, endothelin and C-reactive protein (CRP). Patients not using statins and with or without blood pressure control were also analyzed. RH group showed smaller percentage increase of maximum forearm blood flow (FBF) (endothelial-dependent vasodilatation) than controls (p < 0.05), but no significant difference could be detected between MMH and CG groups on maximum FBF and minimum vascular resistance post-ischemia. RH and MMH groups showed higher resistance averages compared to controls (p < 0.05). Uncontrolled BP in hypertensive patients showed worse results for blood flow and resistance. Endothelial-independent vasodilatation was not affected. Endothelin levels were higher in RH and MMH groups (p < 0.05) not using statins. CRP was significantly higher only in RH compared to CG (p < 0.05). In conclusion patients with severe hypertension and lack of blood pressure control showed greater impairment of endothelial function with higher CRP and endothelin levels.

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.

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). 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. 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). The current study does not support positive effects of RDN on microvascular impairment in TRH.

MPS 08-07 CEREBROVASCULAR RESISTANCE INDEX AND COGNITIVE IMPAIRMENT IN ESSENTIAL HYPERTENSIVE PATIENTS

Objective: To evaluate the relationship between parameters of cerebral blood flow and cognitive function in pts with essential hypertension (EH). Design and Method: Doppler ultrasonography, 24 h blood pressure monitoring were performed in 141 pts (61.8 ± 0.94 years; 78 males) with EH. We measured blood flow velocities (BFV) in media (MCA), anterior (ACA), posterior (PCA) cerebral arteries and calculated cerebrovascular resistance index (CVRI) for each artery. Cognitive function was assessed in all pts by Montreal cognitive assessment (MoCA) test. All patients were divided into 2 groups depending on the MoCA results: group I (n = 79) – MoCA score ≥26, group II (n = 62) - MoCA score < 26. Results: Patients of II gr. had significantly lower BFV min in MCA, ACA, PCA (accordingly: MCA – 0.46 ± 0.03 vs 0.62 ± 0.04 m/s, p < 0.05, ACA – 0.34 ± 0.02 vs 0.45 ± 0.03 m/s, p < 0.05, PCA – 0.25 ± 0.01 vs 0.36 ± 0.02 m/s, p < 0.05) and significantly higher CVRI than pts of I gr. (accordingly: MCA – 169.21 ± 10.28 vs 130.47 ± 8.47 mmHg/m/s, ACA – 271.65 ± 21.32 vs 180.16 ± 20.25 mmHg/m/s, PCA – 407.12 ± 24.28 vs 252.03 ± 21.58 mmHg/m/s, p < 0.05). Changes of BFV max and mean were not significant. MoCA results were related to MCA BFV min (r = −0.46; p < 0.01), CVRI (r = 0.52; p < 0.05). The same relations were between MoCA results and BFV parameters of ACA and PCA. After adjustment for 24 h SBP and DBP, 24hI SBP, variability of nighttime SBP and DBP these relationships were not significant. Multiple regression analysis has shown that CVRI is predictor of cognitive impairment in pts with EH. Conclusions: Cognitive function in patients with EH related to increase vascular resistance manifesting through decrease minimal blood flow and increase vascular resistance indexes in media, anterior, posterior cerebral arteries. These changes are caused by high 24 h SBP and DBP, variability of nighttime SBP and DBP, low SBP 24 h index. CVRI is predictor of cognitive impairment in pts with EH.

Positive effects of aggressive vasodilator treatment of well-treated essential hypertensive patients.

Increased systemic vascular resistance and coronary microvascular dysfunction are well-documented in essential hypertension (EH). We investigated the effect of additional vasodilating treatment on coronary and peripheral resistance circulation in EH patients with high systemic vascular resistance index (SVRI) despite well-treated blood pressure (BP). We enroled patients on stable antihypertensive treatment that were given intensified vasodilating therapy (ACE inhibitor, angiotensin II receptor blocker or calcium channel blocker). Before and following 6 months of intensified therapy, coronary resting and maximal artery flow were measured by transthoracic Doppler echocardiography to calculate coronary flow reserve (CFR) and minimum vascular resistance (C-Rmin). Cardiac output was estimated by inert gas rebreathing to calculate SVRI. Maximal forearm blood flow was determined by venous occlusion plethysmography to calculate minimum vascular resistance (F-Rmin). Patients were assigned into two groups: high-SVRI and low-SVRI subgroups, based on a median split at baseline. Following additional treatment SVRI decreased more in the high-SVRI group than in the low-SVRI group (14.4 vs -2.2%: P=0.003), despite similar baseline ambulatory BP (132/81 mm Hg) and BP reduction (6.5 and 4.6%: P=0.19). F-Rmin remained unchanged (6.5 vs -2.0%: P=0.30), while C-Rmin decreased by 22 and 24% (P=0.80) and CFR increased by 23 and 17% (P=0.16). Thus, intensified vasodilating therapy improved SVRI more in patients with high SVRI than in those with low SVRI. Regardless of SVRI status, the treatment improved cardiac but not forearm dilatation capacity. The substantial improvement of the hypertensive cardiac microvascular dysfunction was not related to the reduction in SVRI.

Pubertal administration of antiserum against nerve growth factor regresses renal vascular remodeling in spontaneously hypertensive rats.

To investigate the role of nerve growth factor (NGF) in the development of hypertensive renal vascular remodeling, antiserum against NGF (anti-NGF) or vehicle was injected at 3 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each treatment in each strain). Flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships at vasodilated perfused kidneys were determined at 10 weeks of age. In the vehicle rats, blood pressure, renal noradrenaline content, the gradient of F-P (minimal vascular resistance at pre- and post-glomerular vasculature) and the X-intercept of P-GFR (preglomerular : postglomerular vascular resistance ratio) were greater in SHR than in WKY rats, although the gradient of P-GFR (glomerular filtration capacity) did not differ significantly between the strains. Blood pressure and renal noradrenaline content were lower in SHR receiving anti-NGF than in SHR receiving vehicle, although such difference was not observed in WKY rats. The gradient of F-P was less but the gradient of P-GFR was greater in SHR receiving anti-NGF compared with SHR receiving vehicle, although the similar differences did not occur in WKY rats. Blood pressure and renal noradrenaline content remained greater in SHR treated with anti-NGF compared with WKY rats treated with vehicle; however, the gradient of F-P did not differ significantly between them. Contrary, anti-NGF did not affect the X-intercept of P-GFR in either strain. In conclusion, NGF could contribute to the genesis of renal vascular remodeling, at least in part, through modification of renal sympathetic activity and blood pressure in SHR.

Coronary Microvascular Dysfunction Is Related to Abnormalities in Myocardial Structure and Function in Cardiac Amyloidosis

ObjectivesThe purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis. BackgroundEffort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD). MethodsThirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product. ResultsCompared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p < 0.0001), and CFR (1.19 ± 0.38 vs. 2.23 ± 0.88; p < 0.0001) and higher minimal coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (<1.3 ml/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased left ventricular mass, and age were the only independent predictors of impaired coronary vasodilator function. ConclusionsCoronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.

Differential effects of age on large artery stiffness and minimal vascular resistance in normotensive and mildly hypertensive individuals

Large artery stiffness and small artery structural changes are both cardiovascular risk factors. Arterial stiffness increases with age and blood pressure (BP), but it is unclear in which way large artery pulse wave velocity (PWV) and peripheral vascular resistance are related and whether age has any influence. In a cross-sectional study, PWV and forearm minimum vascular resistance (Rmin ) was compared with emphasis on the impact of age. Normotensive (n = 53) and untreated hypertensive (n = 23) subjects were included based on 24-h BP measurements. Age ranged from 21 to 79 years with an even distribution from each age decade. PWV was assessed using tonometry. Forearm Rmin was measured by venous occlusion plethysmography at maximal vasodilatation induced by 10 min of ischaemia in combination with skin heating and hand grip exercise. In both normotensive and hypertensive subjects, PWV correlated significantly with age and BP. Based on median age, both groups were assigned into two equally large subgroups. Normotensive older (66 ± 7 years) and younger (35 ± 10 years) persons had different carotid-femoral PWV (7.9 ± 1.8 versus 5.7 ± 0.9 m/s, P<0.01), but similar Rmin values (3.7 ± 0.9 versus 3.6 ± 1.2 mmHg/ml/min/100 ml). Hypertensive older (63 ± 6 years) and younger (40 ± 10 years) also had different PWV (8.0 ± 1.5 versus 6.7 ± 1.1 m/s, P<0.05), but the older had lower Rmin (3.1 ± 0.8 versus 4.7 ± 2.2 mmHg/ml/min/100 ml, P<0.05). In a regression analysis adjusting for age, BP, gender and heart rate, no correlation was seen between PWV and Rmin . The data suggest that age differentially affects PWV and Rmin and that BP can increase in older persons without affecting Rmin .

Renal vascular structural properties and their alterations by removal of uraemic toxins in a rat model of chronic kidney disease

1. Renal vascular structural properties and their alterations by removal of uraemic toxins with AST-120, an oral adsorbent, were examined in subtotal nephrectomized rats. 2. Eight- or 9-week-old Sprague-Dawley rats received 3/4 nephrectomy (n = 18) and thereafter were fed 24.5% protein diet with (AST; n = 9) or without (AST-; n = 9) AST-120 (0.4 g/100 g bodyweight). Sham-operated rats (Sham; n = 9) received the diet without AST-120. At 21-22 weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships were determined for maximally vasodilated, perfused kidneys. 3. The gradient of F-P (minimal renal vascular resistance reflecting the overall luminal dimensions of pre- and post-glomerular vasculature) was lower in AST- than Sham rats. In contrast, the x-intercept (preglomerular : post-glomerular vascular resistance ratio) and gradient (glomerular filtration capacity) of P-GFR did not differ between the two groups. The vascular wall and lumen at the interlobular arteries were greater in AST- than Sham rats. 4. Although the vascular wall and lumen at the interlobular arteries were less in AST than in AST- rats, the gradient of F-P and the x-intercept of P-GFR did not differ between the two groups. In contrast, the glomerular filtration capacity was greater in AST than AST- rats. 5. In conclusion, the lumen of both pre- and post-glomerular resistance vessels increased and glomerular filtration capacity failed to increase in subtotal nephrectomized rats. Uraemic toxins could play an important role in the development of structural alterations in glomeruli rather than renal resistance vessels in chronic kidney disease.

Macro- and microvascular function in habitually exercising systemic lupus erythematosus patients

Objectives: Vascular dysfunction is commonly observed in systemic lupus erythematosus (SLE) patients and may explain the accelerated cardiovascular disease (CVD) risk. It is unknown whether physical activity influences vascular function in SLE patients. We aimed to determine whether habitually exercising SLE patients also demonstrate a reduction in vascular function.Method: This study involved 41 young and middle-aged adults, including 15 healthy controls, 12 sedentary SLE patients, and 14 physically active SLE patients.Results: Flow-mediated dilation (FMD), a measure of macrovascular function, was lower (3.6 ± 1.3 vs. 8.1 ± 1.2%; p < 0.05) and inflammatory markers [C-reactive protein (CRP), interleukin (IL)-12, and tumour necrosis factor (TNF)-α] were higher in sedentary SLE patients than in age-matched healthy controls (p < 0.05). Importantly, FMD and inflammatory markers were not different between physically active SLE patients and healthy controls. There were no group differences in skin reactive hyperaemia (RH) or minimal vascular resistance, both measures of microvascular function. Physically active SLE patients had lower intercellular adhesion molecule (ICAM)-1 concentrations and SLE disease activity scores than their sedentary peers. FMD was inversely associated with IL-6 and IL-10 (both p < 0.05).Conclusions: Significant SLE-associated macrovascular dysfunction was absent in physically active SLE patients. Additionally, vascular function was associated with inflammatory markers, suggesting that the favourable influence of physical activity may be mediated by its effect on inflammation.

Effect of Type 2 Diabetes Mellitus on Epicardial Adipose Tissue Volume and Coronary Vasomotor Function

Patients with coronary artery disease and/or type 2 diabetes mellitus (DM) generally exhibit more epicardial adipose tissue (EAT) than healthy controls. Recently, it has been proposed that EAT affects vascular function and structure by secreting proinflammatory and vasoactive substances, thereby potentially contributing to the development of cardiovascular disease. In the present study, the interrelation of EAT, coronary vasomotor function, and coronary artery calcium was investigated in patients with and without DM, who were evaluated for coronary artery disease. Myocardial blood flow (MBF) was assessed at rest and during adenosine-induced hyperemia using [(15)O]-water positron emission tomography combined with computed tomography to quantify coronary artery calcium and EAT in 199 patients (46 with DM). In this cohort (mean age 58 ± 10 years), the patients with DM had a greater body mass index, heart rate, and systolic blood pressure at rest (all p <0.05). Coronary artery calcium and the EAT volumes were comparable between those with and without DM. Both patient groups showed comparable MBF at rest and coronary vascular resistance. A lower hyperemic MBF and coronary flow reserve (CFR) and greater hyperemic coronary vascular resistance (all p <0.05) was observed in the patients with DM. A pooled analysis showed a positive association of EAT volume with hyperemic coronary vascular resistance but not with the MBF at rest, hyperemic MBF, or coronary vascular resistance at rest. In the group analysis, the EAT volume was inversely associated with hyperemic MBF (r = -0.16, p = 0.05) and CFR (r = -0.17, p = 0.04) and positively with hyperemic coronary vascular resistance (r = 0.26, p = 0.002) only in patients without DM. Multivariate regression analysis, adjusted for age, gender, and body mass index, showed an independent association between the EAT volume and hyperemic MBF (β = -0.16, p = 0.02), CFR (β = -0.16, p = 0.04), and hyperemic coronary vascular resistance (β = 0.25, p <0.001) in the non-DM group. In conclusion, these results suggest a role for EAT in myocardial microvascular dysfunction; however, once DM has developed, other factors might be more dominant in contributing to impaired myocardial microvascular dysfunction.

Abstract 502: Salt-Excess Induced Exacerbated Hypertension Prevention by Telmisartan in Spontaneously Hypertensive Rats

The effects of angiotensin receptor blocker (AGA), diuretic, a calcium antagonist (CA), and their combination were evaluated on the progression of cardiovascular damage in spontaneously hypertensive rats (SHR) given salt-excess. To this end, 8-week male SHR rats were divided into 7 groups. The control group (C) received regular NaCl (0.6%) diet. All other groups were given 8% NaCl rat chow. In addition, Group 2 (HS) was given placebo, Group 3 (T) the AGA telmisartan (10 mg/kg/day), Group 4 (D) received the chlorothiazide (80 mg/kg/day), Group 5 (T+D) telmisartan plus diuretic, Group 6 (A) was given the CA amlodipine (10 mg/kg/day), and Group 7 (T+A) telmisartan plus amlodipine. All treatments lasted 8 weeks. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve (CFR), minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall (-dP/dT) were all adversely affected by salt-loading (Table). Increased left ventricular weight (LVWI) with marked cardiac fibrosis was also found with salt overload. Telmisartan normalized all indices except MAP, whereas diuretic and amlodipine only partially restored cardiac function and mass. Combination therapy with telmisartan and either diuretic or amlodipine also normalized all indices including arterial pressure (Table). These data show that: (1) cardiovascular and renal damage induced by salt-excess in SHR were not pressure dependent; and (2) compared with the CA and diuretic, AGA was more effective in this model suggesting that local renin in target organs participated in salt-induced hypertension.

Telmisartan Prevents Excess-Salt-Induced Exacerbated (Malignant) Hypertension in Spontaneously Hypertensive Rats

The effects of angiotensin receptor blocker, diuretic, a calcium antagonist, and their combination were evaluated on the progression of cardiovascular and renal damage in spontaneously hypertensive rats (SHRs) given excess salt. To this end, 8-week male SHRs were divided into 7 groups. The control group (C) received normal NaCl (0.6%) diet. All other groups were given 8% NaCl rat chow. In addition, group 2 was given placebo (tap water alone), group 3 the angiotensin receptor antagonist telmisartan (10 mg/kg per d), group 4 received the diuretic chlorothiazide (80 mg/kg per d), group 5 was given telmisartan plus the diuretic, group 6 was given the calcium antagonist amlodipine (10 mg/kg per d), and group 7 was given telmisartan plus amlodipine. All treatments lasted for 8 weeks. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve, minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall were all adversely affected by salt loading. Increased left ventricular mass with marked cardiac fibrosis was also found in the salt-overloaded SHR group. Telmisartan normalized all indices except MAP, whereas diuretic and amlodipine only partially restored cardiac functional and mass indexes. Combination therapy with telmisartan and either diuretic or amlodipine also normalized all indices including arterial pressure. These data suggest that (1) cardiovascular damage induced by excess salt in the SHRs was not pressure dependent; (2) compared with the calcium antagonist and diuretic, blockade of angiotensin receptors was extremely effective in this model.

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

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). 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. 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 ± 3.2%) were significantly associated with changes in C-Rmin (-9.3 ± 4.9%) and LVMI (-6.9 ± 1.7%) (P < 0.01), but not to either 24-h BP, SVRI or CFR. 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.

Carotid artery intima-media thickness, but not coronary artery calcium, predicts coronary vascular resistance in patients evaluated for coronary artery disease

There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR). We evaluated 120 patients (mean age 56 ± 9 years, 58 men) without a documented history of CAD in whom obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress (15)O-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 ± 6, 27 ± 11, and 28 ± 9 mmHg mL(-1)min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 ± 9, 27 ± 8, 32 ± 10, and 32 ± 7 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR. C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.

Leaky vessels: how the brain deals with pregnancy under pressure

Leaky vessels: how the brain deals with pregnancy under pressure