The impact of blood pressure variability on subclinical ventricular, renal and vascular dysfunction, in patients with hypertension and diabetes.
ABSTRACT: Blood pressure variability (BPV) was proved as a cardiovascular risk factor. One of its mechanisms is related to arterial stiffness and ventriculo-arterial coupling; however its impact on subclinical cardiovascular dysfunction has not been evaluated yet.To assess the relationship between BPV on 24 hours, and subclinical left ventricle (LV), renal, and vascular dysfunction in diabetic and hypertensive patients.We studied 56 patients (57±9 years, 29 men) with mild-to-moderate hypertension and type 2 diabetes, no cardiovascular disease, normal ejection fraction and normal renal function. 24 hours ambulatory blood pressure monitoring (ABPM) was used to assess BPV, daytime (d) and night time (n), by: 1. mean (M); 2. standard deviation of mean (SD); 3. variance (Vr); 4. coefficient of variation (CV); 5. day/night variation: reverse dippers, non-dippers, dippers and extreme dippers; conventional and 2D speckle tracking echo to assess LV function; myocardial deformation was measured as global longitudinal strain (GLS). Endothelial (flow mediated dilation, FMD) and arterial function (intima media-thickness, IMT; pulse wave velocity, PWV), microalbuminuria were tested.Daytime BPV correlates inversely with subclinical myocardial function evaluated through GLS. Daytime systolic BPV correlates positively with IMT (all rho > 0.30, all p < 0.05). Also, there is a significantly inverse correlation between mean BP and GLS. We found a direct correlation between mean BP, but not BPV, and microalbuminuria (all rho > - 0.30 and all p < 0.05). We found no correlation between BPV and FMD, PWV. There were no differences for GLS, microalbuminuria and FMD between dipper groups.In diabetic patients with mild-to-moderate hypertension, increased daytime blood pressure variability correlates with subclinical left ventricular dysfunction and arterial function (IMT), while microalbuminuria correlates with elevated blood pressure, but not with blood pressure variability.
Project description:The aim of this study was to examine the association of night-time systolic blood pressure (BP) with subclinical cardiac dysfunction measured by global longitudinal strain (GLS) and subclinical vascular damage measured by carotid intima-media thickness (CIMT) and carotid plaques.GLS was measured by speckle-tracking analysis of echocardiogram images. CIMT was measured at the distal 1?cm of the common carotid artery. The presence of carotid plaques was recorded. Philips QLAB cardiac and vascular ultrasound quantification software was used for analysis. The association of night-time systolic BP with GLS, CIMT and carotid plaques was assessed using linear and logistic regression.Fifty (response rate 63%) individuals took part in this study. In univariable models, night-time systolic BP was significantly associated with GLS [? coefficient 0.85 for every 10?mmHg increase, 95% confidence interval (CI): 0.3-1.4] and carotid plaques (odds ratio 1.9 for every 10?mmHg increase, 95% CI: 1.1-3.2). Univariable analysis of daytime systolic BP did not show any statistically significant associations. In age-adjusted and sex-adjusted models, the association for night-time systolic BP and GLS remained significant (? coefficient 0.68 for every 10?mmHg increase, 95% CI: 0.1-1.3). The association for carotid plaques was no longer statistically significant. In multivariable models, findings were diminished.Our results suggest a trend towards an association between night-time systolic BP and subclinical cardiac and vascular disease. When assessing ambulatory blood pressure monitoring results, the absolute night-time systolic BP seems to be a better prognostic parameter than daytime systolic BP, but ultimately a large randomised controlled trial involving chronotherapy is necessary to fully address this.
Project description:Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ? 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.
Project description:BACKGROUND:Subclinical hypothyroidism (SHT) may increase the risk of cardiovascular disease. We compared endothelial function between SHT patients and euthyroid individuals, and evaluated the effects of levothyroxine therapy on endothelial function in the patients. MATERIALS AND METHODS:In a quasi-experimental study, flow-mediated dilatation (FMD) and intima-media thickness (IMT) were assessed in SHT patients and healthy controls (n = 25 in each group). Patients then received levothyroxine (50 ?g/day) for 2 months, and the FMD and IMT assessments were repeated. RESULTS:Patients and controls were similar in IMT (0.56 ± 0.09 vs. 0.58 ± 0.08 mm, P = 0.481), but FMD was lower in patients than in controls (4.95 ± 2.02 vs. 6.50 ± 2.57%, P = 0.011). A significant increase was observed in FMD (4.11 ± 2.37%, P = 0.001), but not in IMT (-0.004 ± 0.020 mm, P = 0.327), after levothyroxine therapy among the patients. CONCLUSIONS:Patients with SHT have endothelial dysfunction which responds to levothyroxine therapy. Randomized placebo-controlled trials are needed to confirm these findings.
Project description:The pooled cohort Atherosclerotic Cardiovascular Disease (ASCVD) risk calculator is designed to improve cardiovascular risk estimation compared with the Framingham Risk Score, particularly in blacks. Although the ASCVD risk score better predicts mortality and incident cardiovascular disease in blacks, less is known about its performance for subclinical vascular disease measures, including arterial stiffness and carotid intima-media thickness. We sought to determine if the ASCVD risk score better identifies subclinical vascular disease in blacks compared with the Framingham risk score. We calculated both the Framingham and ASCVD cohort risk scores in 1,231 subjects (mean age 53 years, 59% female, 37% black) without known cardiovascular disease and measured the extent of arterial stiffness, as determined by pulse wave velocity (PWV), central pulse pressure (CPP), and central augmentation index (CAIx), and subclinical atherosclerosis, as determined by carotid-IMT (C-IMT). Compared with whites, blacks had higher CAIx (23.9?±?10.2 vs 22.1?±?9.6%, p?=?0.004), CPP (36.4?±?10.5 vs 34.9?±?9.8?mmHg, p?=?0.014), PWV (7.6?±?1.5 vs 7.3?±?1.3?m/s, p?=?0.004), and C-IMT (0.67?±?0.10 vs 0.65?±?0.10?mm, p?=?0.005). In a multivariable analysis including race and Framingham risk score, race remained an independent predictor of all measures of subclinical vascular disease; however, models with race and the ASCVD risk score showed that race was not an independent predictor of subclinical vascular disease. In conclusion, greater subclinical vascular disease in blacks was not estimated by the Framingham risk score. The new ASCVD risk score provided a better estimate of racial differences in vascular function and structure.
Project description:OBJECTIVES:To investigate the effect of smoking on vascular response to transradial coronary angiography (TCA). BACKGROUND:Cigarette smoking is the most important modifiable cardiovascular risk factor associated with endothelial dysfunction. METHODS:Radial artery flow-mediated vasodilation (RA-FMD), local stiffness (fractional diameter change), intima-media thickness (IMT), luminal and external arterial diameter were measured in 40 current smokers (CS) and former smokers (FS) at 6-14 months at the site of previous TCA and contralateral control artery. Vascular regenerative capacity was studied as chemotactic cell migration in vitro and ex vivo (n=10) and the time course of endothelial functional recovery following RA-FMD up to 72 h after TCA (n=10). RESULTS:At 10 ± 3 months after TCA, subjects exhibited significant local stiffening and increased IMT as compared to the control arm. These late structural changes were significantly more pronounced in CS as compared to FS. IMT thickening correlated with packyears, number of daily cigarettes, and inversely with RA-FMD. Nitric oxide synthase (NOS)-dependent chemotaxis of CS' circulating angiogenic cells was impaired. Ex vivo incubation of endothelial cells with CS' plasma inhibited NOS-dependent endothelial wound closure and chemotaxis. In vivo, TCA acutely decreased RA-FMD. At 24 h, RA-FMD had recovered in FS but remained impaired at 24 h and only recovered at 48 h in CS. CONCLUSION:In active smokers, transradial coronary angiography is associated with delayed early recovery from transient endothelial dysfunction, decreased NOS-dependent vascular regeneration, and late arterial remodeling pointing towards potential harmful effects of transradial coronary angiography on vascular function in distinct subsets of patients.
Project description:Whether arterial stiffness correlates with mild-to-moderate CKD and albuminuria in the community is unclear. We studied the association between arterial stiffness and mild-to-moderate CKD and albuminuria in the Framingham Heart Study. CKD was present in 6.7% (181 of 2682) of participants and microalbuminuria was present in 8.2% (479 of 5818). The measures of arterial stiffness were the carotid femoral pulse wave velocity, forward pressure wave amplitude, central pulse pressure, augmentation pressure, augmentation index, and mean arterial pressure. In cross-sectional analyses, arterial stiffness did not associate with CKD (defined by estimated GFR <60 ml/min/1.73 m(2)) in either age- and gender-adjusted or multivariable-adjusted linear regression models. Carotid femoral pulse wave velocity associated with both urinary albumin-to-creatinine ratio and microalbuminuria (P < 0.0001 after multivariable adjustment). In longitudinal analyses, we used logistic regression models to examine the associations between baseline arterial stiffness measures (exposure variables) and incident CKD or microalbuminuria (n = 1675 for CKD analyses and n = 1252 for microalbuminuria analyses). Baseline arterial measures did not associate with incident CKD or incident microalbuminuria. In summary, arterial stiffness correlates with albuminuria but not with mild-to-moderate CKD.
Project description:Our aim was to analyze the relationship between abdominal obesity and general obesity, with subclinical atherosclerosis, arterial stiffness and wave reflection in healthy, diabetics and hypertensive subjects.A cross-sectional descriptive study was made of 305 individuals (diabetics 32.8%, hypertensive subjects 37.0% and healthy individuals 30.2%).Body mass index (BMI), waist circumference (WC), body fat percentage (BFP) and waist/height ratio (WHtR). Arterial stiffness was assessed according to pulse wave velocity (PWV), intima-media thickness of the common carotid artery (C-IMT), augmentation index (central and peripheral), ankle-brachial index (ABI), and central and peripheral pulse pressure.WC and WHtR showed a positive correlation to PWV and C-IMT in the studied groups. After adjusting for age, gender, high sensitivity c-reactive protein, serum glucose and the presence of diabetes, hypertension, smoking, dyslipidemia, antidiabetic drugs, lipid-lowering drugs, and atherosclerotic plaques, it was seen that for every 0.1 point increase in WHtR, and for every cm increase in WC, the PWV increased 0.041 and 0.029 m/sec, and C-IMT increased 0.001 mm and 0.001 mm, respectively.The measures of abdominal obesity (WHtR and WC) correlates better than BMI and BFP with arterial stiffness evaluated by PWV, and with subclinical atherosclerosis evaluated by C-IMT, independently of the presence of diabetes or hypertension.Clinical Trials.gov Identifier: NCT01325064.
Project description:Lipoprotein(a) [Lp(a)] is an established risk factor for coronary disease and stroke, but mechanisms underlying this association are unknown. We examined the association of Lp(a) with early atherosclerosis by using conventional epidemiologic analysis and a Mendelian randomization analysis. The latter utilized genetic variants that are associated with Lp(a) to estimate causal effect.A prospective population-based cohort study of 939 men and 1141 women was conducted. Lp(a) was measured repeatedly at mean ages 17 and 38 years. Measurements of carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) at mean ages 32 and 38 years were used to determine the level and 6-year progression of subclinical atherosclerosis. Lp(a)-related genetic variant, rs783147, was identified by a genome wide association analysis (P = 3.1 × 10???), and a genetic score was constructed based on 10 Lp(a)-related variants. Mendelian randomization test was performed using a two-stage instrumental variables analysis.rs783147 and the genetic score were strong instruments for nonconfounded Lp(a) levels (F-statistics 269.6 and 446.0 in the first-stage instrumental variable analysis). However, Lp(a) levels were not associated with the levels of or change in IMT or FMD in any of the conventional and instrumental variables tests. The null finding was observed both with rs783147 and the genetic score as instruments and remained unchanged after adjustment for clinical characteristics, such as age, sex, HDL and LDL cholesterol, ApoB, systolic and diastolic blood pressure, diabetes and smoking.Data from conventional and Mendelian randomization analyses provide no support for early atherogenic effects of increased Lp(a) levels.
Project description:<h4>Background</h4>Asthma is associated with an increased cardiovascular disease (CVD) risk in adults, but the impact of asthma and atopic conditions on CVD risk in children is less well established. We hypothesized that children in the Childhood Origins of Asthma (COAST) Cohort with asthma and atopic conditions would have early carotid arterial injury.<h4>Methods</h4>The COAST study is a longitudinal birth cohort of children at increased risk of developing asthma. Children underwent ultrasonography measuring far wall right carotid bifurcation (RCB) and common carotid artery (RCCA) intima-media thickness (IMT; a measure of arterial injury). Multivariable linear regression models adjusted for age, gender, race, blood pressure, and body-mass index were used to assess associations of asthma and markers of arterial injury.<h4>Results</h4>The 89 participants were a mean (standard deviation) 15.3 (0.6) years old and 42% were female; 28 asthmatics had atopic disease, 34 asthmatics were without other atopic disease, and 15 non-asthmatics had atopic disease. This study population was compared to 12 controls (participants free of asthma or atopic disease). Compared to controls (589 ?m), those with atopic disease (653 ?m, p = 0.07), asthma (649 ?m, p = 0.05), or both (677 ?m, p = 0.005) had progressively higher RCB IMT values (ptrend = 0.011). In adjusted models, asthmatic and/or atopic participants had significantly higher RCB IMT than those without asthma or atopic disease (all p?0.03). Similar relationships were found for RCCA IMT.<h4>Conclusion</h4>Adolescents with asthma and other atopic diseases have an increased risk of subclinical arterial injury compared to children without asthma or other atopic disease.
Project description:BACKGROUND:Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. METHODS:We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-UtwMVO), at peak (%dpTw-UtwPEF) and end of early LV diastolic filling (%dpTw-UtwEDF) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP. RESULTS:After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-UtwMVO (31 ± 10 vs. 40 ± 14), %dpTw-UtwPEF (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = - 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations) after 6-month treatment. CONCLUSIONS:Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683.