Prediction of Future Overt Pulmonary Hypertension by 6-Min Walk Stress Echocardiography in Patients With Connective Tissue Disease.

BACKGROUND: Early detection of pulmonary hypertension (PH) in connective tissue disease (CTD) is crucial to ensuring that patients receive timely treatment for this progressive disease. Exercise stress tests have been used to screen patients in an attempt to identify early-stage PH. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (Q) responses as having the potential to assess the disease state. OBJECTIVES: This study hypothesized that pulmonary circulation pressure-flow relationships obtained by 6-min walk (6MW) stress echocardiography would better delineate differential progression of PH and predict development of PH during follow-up. METHODS: We prospectively performed 6MW stress echocardiographic studies in 78 CTD patients (age 58 ± 12 years; 9% male) at baseline and follow-up. All patients underwent yearly echocardiographic follow-up studies for up to 5 years. RESULTS: During a median period of 32 months (range: 15 to 62 months), 16 patients reached the clinical endpoint of development of PH and none died during follow-up. PH was confirmed by right heart catheterization in all 16 patients (mPAP ≥25 mm Hg and pulmonary capillary wedge pressure ≤15 mm Hg). In a Cox proportional-hazards survival model, 6MW distance (hazard ratio [HR]: 0.99; p = 0.010), early diastolic tricuspid annulus motion velocity (HR: 0.79; p = 0.025), and ΔmPAP/ΔQ by 6MW stress (HR: 1.10; p = 0.005) were associated with development of PH. In sequential Cox models, a model on the basis of 6MW distance (chi-square, 6.6) was improved by ΔmPAP/ΔQ (chi-square: 14.4; p = 0.019). Using a receiver-operating characteristic curve, we found that the best cutoff value of ΔmPAP/ΔQ for predicting development of pulmonary hypertension was >3.3 mm Hg/l/min. CONCLUSIONS: The 6MW stress echocardiography noninvasively provides an incremental prognostic value of PH development in CTD. This is a single-center prospective cohort study. Larger multicenter studies are warranted to confirm this result.

Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension.

BACKGROUND: Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease. METHODS: We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB. RESULTS: The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate. CONCLUSION: The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.

Effects of docosahexaenoic Acid on the endothelial function in patients with coronary artery disease.

AIM: The consumption of n-3 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid DHA), reduces the incidence of cardiovascular events, and reduced serum levels of n-3 PUFA may be associated with an increased risk of cardiovascular events. However, controversy remains regarding which components of PUFA are associated with the endothelial function in patients with coronary artery disease (CAD). We therefore examined the associations between the n-3 and n-6 PUFA levels and CAD. METHODS: We retrospectively reviewed 160 consecutive Japanese patients with CAD whose endothelial function was measured according to the percent change in flow-mediated dilation (FMD) and the serum levels of n-3 PUFA, including eicosapentaenoic acid (EPA) and DHA, and n-6 PUFA, including arachidonic acid (AA) and dihomo-gamma-linolenic acid (DHLA). RESULTS: A single regression analysis showed no relationships between the FMD and the serum levels of PUFA, including EPA, DHA, AA and DHLA. In contrast, a multiple regression analysis showed that the DHA level was a positive (＜ 0.01) and age was a negative (P ＜ 0.001) contributor to an increased FMD; however, sex, body mass index, systolic and diastolic blood pressure, current/past smoking and the levels of HbA1c, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, EPA, AA and DHLA did not significantly affect the outcome. CONCLUSIONS: The serum level of DHA is associated with the endothelial function evaluated according to the FMD in patients with CAD, thus suggesting that a low serum level of DHA may be a predictive biomarker for endothelial dysfunction.

Tricuspid annular motion velocity as a differentiation index of hypertrophic cardiomyopathy from hypertensive heart disease.

BACKGROUND: Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are the most frequently encountered entities presenting left ventricular hypertrophy in routine echocardiographic examination, and their differentiation is sometimes difficult. Abnormalities in right ventricular (RV) myocardium have been reported frequently in patients with HCM more than in those with HHD. We therefore hypothesized that tricuspid annular motion (TAM) velocity determined by pulsed tissue Doppler echocardiography can be used to detect RV dysfunction in HCM and discriminate these etiologies. METHODS: TAM velocities were compared among clinically stable patients with 60 HCM and 60 HHD patients as well as 60 age-matched healthy controls. Peak systolic, early diastolic (TAM-e'), and atrial systolic velocities were measured. RV myocardial performance index was measured by tissue Doppler method. To more accurately differentiate HCM from HHD, electrocardiographic findings and brain natriuretic peptide levels, which can both be examined simply and noninvasively, were investigated in addition to echocardiography. RESULTS: RV wall thickness of the HCM group was greater than the HHD group (p=0.092), while there was no significant difference in RV myocardial performance index between the HCM and HHD groups (p=0.606). TAM-e' was significantly lower in the HCM group than in HHD and control groups (p=0.001). To differentiate HCM from HHD, TAM-e' was a powerful predictor as per multivariate logistic regression analysis (hazard ratio, 0.665; p<0.001) of parameters other than those of left ventricular parameters, and the area under the receiver operating characteristic curve (AUC) was 0.686 and the best cut-off value was ≤8.0cm/s (62% sensitivity, 65% specificity). Multivariate logistic analysis revealed that electrocardiographic ST-T changes were the next most effective marker for differentiating HCM after TAM-e'. When TAM-e' and ST-T changes were combined, the AUC increased to 0.748. CONCLUSIONS: TAM-e' is a potentially useful index to differentiate HCM from HHD.

Plasma microRNA-100 is associated with coronary plaque vulnerability.

BACKGROUND: Although numerous studies have reported altered plasma levels of various microRNAs (miRNAs) in patients with cardiovascular disease, there are no data on the relationship between plasma miRNAs and vulnerable coronary plaque. In this study, we investigated whether plasma miRNAs might be a sensitive marker of coronary plaque vulnerability. METHODS AND RESULTS: Integrated backscatter intravascular ultrasound (IB-IVUS) was performed in 32 consecutive patients with angina pectoris who underwent percutaneous coronary intervention. Three-dimensional analysis of IB-IVUS was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Circulating miRNAs were measured in EDTA-plasma simultaneously obtained from the aorta and the coronary sinus (CS). Muscle-enriched (miR-133a, miR-208a, miR-499), vascular-enriched (miR-92a, miR-100, miR-126, miR-127, miR-145), and myeloid cell-enriched miRNAs (miR-155, miR-223) were measured. Plasma miR-100 was higher in the CS than in the aorta, but there were no significant differences in the levels of other miRNAs between the aorta and CS. Plasma miR-100 in the aorta was positively correlated with %LV (r=0.48, P<0.01) and negatively correlated with %FV (r=-0.41, P<0.05). Importantly, transcoronary concentration gradient of circulating miR-100 was more strongly correlated with %LV (r=0.53, P<0.01) and %FV (r=-0.56, P<0.01). CONCLUSIONS: miR-100 might be released into the coronary circulation from vulnerable coronary plaques. This study provides insights into the role of miRNAs in coronary atherosclerotic disease.

Age- and gender-specific changes of tricuspid annular motion velocities in normal hearts.

BACKGROUND: Mitral annular motion (MAM) and tricuspid annular motion (TAM) velocities obtained by pulsed tissue Doppler echocardiography have been used to evaluate left ventricular (LV) and right ventricular (RV) functions. Although TAM velocity has been clinically applied for evaluating various cardiac diseases, the effects of age and gender remain unclear. Therefore, we aimed to determine the effects of age and gender on TAM velocity in normal hearts. METHODS: We randomly selected 265 subjects (mean age, 59 years; range, 20-89 years) without abnormal clinical, electrocardiographic, and echocardiographic findings from a pool of subjects who had undergone transthoracic echocardiography. They were classified into four age groups: 20-39, 40-59, 60-79, and >80 years. Pulsed wave Doppler was applied to obtain MAM velocity of the lateral side and TAM velocity of the RV free wall side. The peak systolic (s'), early diastolic (e'), and atrial systolic (a') velocities of MAM and TAM were measured in all subjects. RESULTS: While MAM-s' (r=-0.267, p<0.001) correlated with age, TAM-s' did not (p=0.755). TAM-s' in any age groups had no significant gender differences. TAM-e' (r=-0.447, p<0.001) and MAM-e' (r=-0.724, p<0.001) correlated with age, respectively. In those aged 40-59 years, both TAM-e' (p=0.002) and MAM-e' (p=0.048) in females were significantly higher than those in males. The gender differences diminished in the ≥60 years age groups. CONCLUSIONS: There was no age-associated decline in TAM-s', while TAM-e' varied with age and gender as did MAM-e'. Although the same criteria for the TAM-s' can be used for identifying abnormal RV systolic function regardless of age and gender, age and gender differences must be considered when one utilizes the TAM-e' for the diagnosis or management of cardiovascular disease.

Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease.

BACKGROUND: Recent studies have shown that intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced risk of cognitive impairment and coronary artery disease (CAD); however, it is currently unknown whether reduced serum n-3 PUFA is associated with cognitive impairment in patients with CAD. METHODS: We retrospectively evaluated cognitive function with the mini-mental state examination (MMSE), serum levels of PUFAs (including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], dihomogammalinolenic acid [DGLA], and arachidonic acid [AA]), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking), and parameters of cardiac function (left ventricular ejection fraction and brain natriuretic peptide levels) in 146 Japanese CAD patients. The associations between the MMSE scores and the other parameters were evaluated. RESULTS: Pearson correlation analysis showed that EPA (R = 0.25, P <0.01), EPA/AA ratio (R = 0.22, P = 0.01), and left ventricular ejection fraction (R = 0.15, P = 0.04) were positively associated with MMSE score, and that age (R = -0.20, P <0.01) and brain natriuretic peptide levels (R = -0.28, P <0.01) were inversely associated with MMSE score. Multiple regression analysis showed that age (P <0.05) was negatively associated with MMSE score, while EPA (P <0.01) and EPA/AA ratio (P <0.05) were positively associated with MMSE score; however, sex; body mass index; left ventricular ejection fraction; levels of DHA, AA, and DGLA; DHA/AA ratio; brain natriuretic peptide; and presence of hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking were statistically excluded. CONCLUSIONS: Serum EPA concentration is associated with cognitive function in patients with CAD, suggesting that a low serum EPA level is a risk factor for cognitive impairment independent of cardiac function, including left ventricular ejection fraction. This correlation potentially lends further support to a role of dietary n-3 PUFAs in preventing the cognitive decline in CAD patients.

Left main coronary artery compression syndrome with an incomplete atrioventricular septal defect presenting as angina induced by hyperthyroidism.

We herein report the case of a 29-year-old woman who was diagnosed with incomplete atrioventricular septal defect and extrinsic compression of the left main coronary artery (LMCA) with chest pain due to postpartum thyroiditis. She exhibited chest pain with ST elevation, and coronary computed tomography showed that the LMCA was compressed between the dilated pulmonary artery and aorta. After her hyperthyroidism was treated, her chest pain resolved. Surgical repair of endocardiosis and coronary bypass grafting were performed. On the one-year follow-up visit, the dilation of the pulmonary artery and right heart was decreased. It is important to consider the possibility of compression of the LMCA in patients presenting with pulmonary hypertension and chest pain.

Pre-load stress echocardiography for predicting the prognosis in mild heart failure.

OBJECTIVES: This study sought to introduce and confirm the efficacy of pre-load stress echocardiography with leg-positive pressure (LPP) for improving risk stratification of patients with mild stable heart failure. BACKGROUND: Heart failure patients with mild symptoms and a poor prognosis should be identified and treated aggressively to improve clinical outcome. METHODS: We performed transthoracic echocardiography with LPP in 202 patients with chronic cardiac disease. Twenty-two of these patients also underwent cardiac catheterization, and left ventricular pressure was measured during LPP along with simultaneous Doppler recordings. Patients were classified into 3 groups on the basis of their left ventricular (LV) diastolic dysfunction as assessed by transmitral flow velocity: restrictive or pseudonormal (PN) at rest, impaired relaxation (IR) at rest and during LPP (stable IR), and IR at rest and PN during LPP (unstable IR). Clinical outcome was compared among these groups. RESULTS: The LPP increased LV end-diastolic pressure from 15.8 ± 4.7 mm Hg to 20.5 ± 5.0 mm Hg in the unstable IR group and from 10.5 ± 2.6 mm Hg to 14.7 ± 3.8 mm Hg in the stable IR group (both p < 0.001). During an average follow-up of 548 ± 407 days, 5 patients had cardiac death, 37 had acute heart failure, 4 had an acute myocardial infarction, and 7 had a stroke. The all-cause cardiac event rate in unstable IR was higher than in stable IR (p < 0.001), and was similar in the PN group (p = 0.81). Event-free survival was significantly lower in unstable IR than in stable IR (p = 0.003). In a Cox proportional hazards model, unstable IR was an independent predictor of all-cause cardiac events (hazard ratio: 8.0; p < 0.001). CONCLUSIONS: The left LV end-diastolic pressure-volume relationship can be estimated by changes in transmitral flow velocity during LPP. Thus, pre-load stress echocardiography using LPP provides additional prognostic information in mild heart failure beyond that provided by conventional Doppler echocardiography at rest.

High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.

Excess parathyroid hormone (PTH), known as primary hyperparathyroidism (pHPT), results in hypercalcemia and bone loss. Recent studies have shown that PTH is associated with the occurrence of hypertension in Western countries; however, controversy remains regarding high serum levels of PTH and calcium as risk factors for hypertension in Japanese patients. We retrospectively enrolled 114 consecutive Japanese patients who visited our hospital for examination and treatment of hypercalcemia and/or hypertension with serum calcium levels ≥ 9.8 mg/dL. To estimate the prevalence of hypertension, the patients were categorized according to calcium levels into hypercalcemic (10.2-13.4 mg/dL) and normocalcemic (9.8-10.1 mg/dL) groups, which were further categorized into high PTH (50-440 pg/mL) and low PTH (8-49 pg/mL) groups. The prevalence of hypertension was higher in patients with hypercalcemia than in patients with normocalcemia in both the high and low PTH groups. The prevalence of hypertension was higher in patients with high serum PTH levels than in patients with low serum PTH levels in both the hypercalcemic and normocalcemic groups. Logistic multiple regression analysis determined that serum calcium (P < 0.05) and PTH (P < 0.01) levels were positive contributors to hypertension. In conclusion, high serum levels of PTH and calcium are risk factors for hypertension in Japanese patients.

Augmentation index does not reflect risk of coronary artery disease in elderly patients.

BACKGROUND: Augmentation index (AI) has been used as a clinical index of arterial stiffness and has been reported to be an independent predictor of cardiovascular events, but some investigators have reported that AI is not a useful marker to identify coronary artery disease (CAD) in elderly patients. The majority of CAD patients are elderly people, therefore the aim of this study was to examine whether AI is a useful marker to identify the risk of CAD. METHODS AND RESULTS: A total of 120 patients (69±10 years of age; 83 male) who underwent cardiac catheterization for suspected CAD were enrolled. Invasive central blood pressure (BP) was measured using a fluid-filled catheter. Non-invasive AI was calculated by the SphygmoCor (AtCor Medical) system at the end of catheterization. Subjects consisted of 99 patients with CAD and 21 patients without CAD. There was no significant difference in AI between the CAD and the non-CAD groups (24±10 vs. 24±14%). Non-invasive systolic central BP was lower than the invasive systolic central BP (115±18 vs. 130±23 mmHg, P<0.001) in all patients. Non-invasive diastolic central BP was greater than the invasive diastolic central BP (67±10 vs. 63±10 mmHg, P<0.001). CONCLUSIONS: In elderly patients, AI may not be a useful marker to identify CAD.

Pentraxin 3 is a local inflammatory marker in atrial fibrillation.

Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3 production in the left atrium might reflect the local inflammation of AF.

Multimodality imaging of biatrial myxomas in an asymptomatic patient.

Myxomas are located in the left atrium in 75-80% of cases and almost always present with signs and symptoms of a thromboembolic event. Biatrial myxomas are rare, and their incidence is generally less than 2.5% of all myxomas. We herein present a case of biatrial myxomas as an incidental finding by echocardiography where the patient underwent surgery. Echocardiography continues to be the initial imaging modality for intracardiac masses. Cardiac magnetic resonance provides superior tissue characterization, particularly important in differentiating a myxoma from a thrombus. Appropriate use of these non-invasive imaging modalities may lead to a correct diagnosis and good outcome. .

Massive tricuspid regurgitation due to pacemaker-lead puncture of the tricuspid valve: successful diagnosis by 3-dimensional echocardiography.

An 83-year-old woman presented to our echocardiographic center with symptoms of right heart failure. A dual-chamber DDDR pacemaker had been implanted 9 years earlier. Two-dimensional echocardiography revealed right atrial and ventricular enlargement and massive tricuspid regurgitation with immobilization of the anterior leaflet of the tricuspid valve. Three-dimensional transesophageal echocardiography showed that the pacemaker lead had punctured the leaflet. These echocardiographic findings were confirmed during surgery. The pacemaker lead was transected and removed, and pericardial patch closure of the leaflet hole and tricuspid annuloplasty were performed. The mechanism of regurgitation was elucidated by real-time three-dimensional echocardiography, and surgical repair was straightforward.

Patent foramen ovale diagnosed by real-time three-dimensional contrast transesophageal echocardiography: A case report.

A 67-year-old man was admitted due to insensitiveness of right upper limb and dysarthria, and treated for suspected lacunar infarction or branch atherosclerotic disease. Carotid ultrasonography showed no abnormalities, and agitated contrast transesophageal echocardiography was performed to detect patent foramen ovale (PFO). Intravenously administered microbubbles did not appear in left atrium by 2-dimensional echocardiography, while contrasts were observed in left atrium using 3-dimensional echocardiography. Real-time 3-dimensional contrast transesophageal echocardiography may be the most useful method for the diagnosis of small PFO. .

Plaque-stabilizing effect of angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker in a rabbit plaque model.

AIM: Previous studies have revealed that blockade of the renin angiotensin system attenuates plaque vulnerability and reduces cardiovascular events; however, few studies have compared the effects of an angiotensin-converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) and evaluated combination therapy. The objective of this study was to compare the efficacy and mechanisms of plaque stabilization by ACEI or ARB and to determine the effects of combination therapy. METHODS: Twenty-eight male Japanese white rabbits were fed a high-cholesterol diet after balloon injury of the carotid arteries, then separated into ACEI (n= 7; imidapril 0.5 mg/kg/day), ARB (n= 7; TA606 4.5 mg/kg/day), combination (n= 7; imidapril 0.5 mg/kg/day+TA606 4.5 mg/kg/day), and vehicle (n= 7) groups. RESULTS: No difference in plaque volume was identified among the 4 groups. ACEI or ARB increased the thickness of the fibrous cap, collagen content and the number of smooth muscle cells in the intima (% smooth muscle cell in intima: ACEI, 36.3%; ARB, 36.4%; vehicle, 14.9%), and reduced the accumulation of macrophages (% macrophages in intima: ACEI, 20.1%; ARB, 24.0%; vehicle, 37.9%), suggesting the plaque-stabilizing effects of each drug. ACEI reduced matrix metalloproteinase (MMP)-9 expression and gelatinolytic activity in the intima. While ARB did not change gelatinolytic activity, accumulation ot T cell in the intima was suppressed. Combination therapy did not show additive effects. CONCLUSION: These results suggest that ACEIs and ARBs have similar, but not additive, plaque-stabilizing effects. Each agent showed specific effects, with ACEIs decreasing gelatinolytic activity and ARBs suppressing T cell accumulation.

Angiotensin II promotes aortic valve thickening independent of elevated blood pressure in apolipoprotein-E deficient mice.

BACKGROUND: Valvular aortic stenosis (AS) is not an infrequent condition in the aged population. Activation of renin-angiotensin system (RAS) is presumed to be involved in the development of AS; however, direct evidence seems to be limited. We herein examined the effect of the administration of angiotensin II (Ang II) on the development of aortic valve thickening in apolipoprotein-E (ApoE)-deficient mice. METHODS AND RESULTS: Male ApoE-deficient mice were divided into three groups: control (saline, n = 8), mice that were administered low-dose Ang II (500 ng/kg/min, n = 11), and those with high-dose Ang II (1000 ng/kg/min, n = 11) administration for 4 weeks. Administration of high-dose, but not low-dose, Ang II significantly induced aortic valve thickening. It was found that in the aortic valve leaflets of high-dose Ang II group, integrity of endothelial cells was impaired and the number of myofibroblasts was increased. These phenomena induced by high-dose Ang II were suppressed by Ang II type 1 receptor blocker olmesartan (n = 15), but not by the dilatator, hydralazine (n = 13). Olmesartan also suppressed dilatation of aortic diameter, although it did not significantly affect the plaque area, in the abdominal aorta in ApoE-deficient mice. CONCLUSION: Administration of Ang II to genetically hyperlipidemic mice induced aortic valve thickening by a pressor-independent mechanism. Role of RAS activation in the development of AS in dyslipidemic patients should further be investigated.