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KEY POINTS: The vasodilatory response to reactive hyperaemia is impaired with advancing age, but it is unclear whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response. Using new technology that allows detailed WSR measurement, we assessed the WSR-FMD response in healthy older people. Our data show that older people have a markedly altered and diminished WSR response to reactive hyperaemia compared to young people, but reduced WSR alone does not fully explain reduced FMD. In young people, WSR appears to be coupled to FMD but, by age â¼65 years, the arterial vasodilatory response has begun to uncouple from the WSR stimulus. These findings point to the importance and utility of comprehensively characterizing the WSR-FMD response when using reactive hyperaemia to assess vascular function, as well as giving new insight into the age-related alteration in vascular function. ABSTRACT: The vasodilatory response to reactive hyperaemia is impaired with age, but it is unknown whether this is because of an altered wall shear rate (WSR) stimulus or an altered flow-mediated dilatation (FMD) response to the WSR stimulus. Inherent difficulties in measuring blood flow velocity close to the arterial wall have prevented detailed assessment of the WSR-FMD response. Using an enhanced multigate spectral Doppler ultrasound system (ultrasound advanced open platform), we aimed to produce new data on the WSR-FMD relationship in healthy older adults. Sixty healthy people, comprising 28 young (27.5 ± 5.5 years) and 32 older (64.9 ± 3.7 years) individuals, underwent FMD assessment. Raw data were post-processed using custom-designed software to obtain WSR and diameter parameters. The data revealed that older people have a much altered and diminished WSR response to reactive hyperaemia compared to younger people [e.g. WSR peak: 622 (571-673) vs. 443 (396-491) 1/s in young and older respectively; P < 0.05]. However, reduced WSR alone does not appear to fully explain the reduced FMD response in older people because associations between WSR and FMD were few and weak. This was in contrast to young adults, where associations were strong. We conclude that WSR during FMD is much altered and diminished in older people, and there appears to be an 'uncoupling' of WSR from FMD in older people that may reflect a loss of precision in the reactive hyperaemia stimulus-response relationship. These findings also point to the importance and utility of comprehensively characterizing the WSR-FMD response when using reactive hyperaemia to assess vascular function.
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Envelhecimento/fisiologia , Artéria Braquial/fisiologia , Hiperemia , Resistência ao Cisalhamento , Vasodilatação/fisiologia , Adulto , Idoso , Endotélio Vascular/fisiologia , Exercício Físico/fisiologia , Humanos , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Estresse Mecânico , Adulto JovemRESUMO
BACKGROUND: The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL, increased ILs and MMPs trigger structural and functional changes in different parts of cardiovascular (CV) system. To understand better the role of lipids and inflammation in CV organ damage, the present study investigated the inter-relationships between lipids, ILs and MMPs, as well as the associations of lipids, ILs and MMPs with various CV measures, both in diabetic and non-diabetic population (nonT2DM). METHODS: In T2DM patients (N = 191) and nonT2DM subjects (N = 94) were assessed carotid intima-media thickness (cIMT) and inter-adventitial diameter (IADiam), carotid wave speed (ccaWS), carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, LV systolic (s') and early diastolic (e') longitudinal velocities of mitral annulus, together with glycemic control, lipid profile, IL-6, IL-18 and MMP-12. RESULTS: T2DM patients, as compared to nonT2DM subjects, had significantly higher plasma levels of IL-6, IL-18, MMP-12 and lower HDL (P < 0.05-0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e' velocity (P < 0.005-0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = - 0.29 and - 0.42; P < 0.0001). In both populations, MMP-12 was directly associated with IADiam, ccaWS, cfPWV and LV mass (r = 0.42, 0.32, 0.26 and 0.29; P < 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P < 0.01-0.0001 in nonT2DM subjects). In multivariate analysis, MMP-12 remained independently related to IADiam, ccaWS, cfPWV and LV mass in T2DM patients, and to IADiam only in nonT2DM subjects. CONCLUSIONS: This cross-sectional study demonstrated a direct association between ILs and MMP-12, as well as an inverse association between MMP-12 and HDL, both in T2DM patients and in nonT2DM subjects. In T2DM patients, who had higher levels of ILs and MMP-12, the latter was independently related to several structural and functional markers of preclinical CV organ damage.
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Doenças das Artérias Carótidas/etiologia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/etiologia , Dislipidemias/complicações , Mediadores da Inflamação/sangue , Inflamação/complicações , Lipídeos/sangue , Idoso , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/fisiopatologia , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Interleucinas/sangue , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Fatores de Risco , Remodelação Vascular , Remodelação VentricularRESUMO
BACKGROUND: Poor glycemic control is associated with impaired left ventricular (LV) diastolic function in patients with type 2 diabetes mellitus (T2DM). Inappropriate LV mass increase and accelerated aortic stiffening were suggested to participate on deterioration of diastolic function. The present study investigated the inter-relationships between glycemic control, early diastolic and systolic longitudinal velocity of mitral annulus, LV mass and aortic stiffness in T2DM patients free of cardiovascular disease and with preserved LV ejection fraction, and compared them with those observed in healthy volunteers of similar age and sex distribution. METHODS: 125 T2DM patients and 101 healthy volunteers underwent noninvasive measurement of systolic (s') and early diastolic (e') velocities of mitral annulus, LV mass, carotid-femoral pulse wave velocity (cfPWV) and local carotid blood pressure (BP). RESULTS: Forty-four (35.2%) T2DM patients had e' velocity lower than that expected for age (against 7.9% in healthy volunteers; P < 0.0001), 34 (27.2%) had cfPWV higher than that expected for age and mean BP (against 5.9% in healthy volunteers; P < 0.0001), and 71 (56.8%) had LV mass higher than that expected for body size and stroke work (against 17.6% in healthy volunteers; P < 0.0001). Carotid systolic BP was higher in T2DM patients (124 ± 14 vs 111 ± 11 mmHg; P < 0.0001). In multivariate analysis, e' velocity was independently related to age, carotid BP and s' velocity in healthy volunteers, and to male sex, age, carotid BP, heart rate and LV mass in T2DM. Glycosylated hemoglobin (HbA1c) was independently related to cfPWV and LV mass in T2DM patients. T2DM patients with HbA1c ≥6.5% (N = 85) had higher cfPWV (P < 0.05), central BP (P = 0.01), prevalence of LV hypertrophy (P = 0.01) and lower e' and s' velocity (P = 0.001 and <0.05, respectively) as compared to those with HbA1c <6.5%. CONCLUSIONS: One-third of T2DM patients with preserved LV ejection fraction has sign of subclinical LV diastolic dysfunction. HbA1c levels are positively associated with LV mass and aortic stiffness, both of which show a negative independent impact on early diastolic velocity e', the latter through an increase in afterload. T2DM patients with suboptimal glycemic control (HbA1c ≥ 6.5%) have lower diastolic and systolic LV longitudinal performance, together with increased aortic stiffness and a higher prevalence of LV hypertrophy.
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Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/etiologia , Hipertrofia Ventricular Esquerda/etiologia , Hipoglicemiantes/uso terapêutico , Rigidez Vascular , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/fisiopatologia , Diástole , Ecocardiografia Doppler em Cores , Ecocardiografia Doppler de Pulso , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Análise Multivariada , Análise de Onda de Pulso , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the characteristics and the determinants of ED, as measured by PAT. METHODS: We measured basal and post-ischemic digital pulse amplitude (EndoPAT(®)) in a mixed outpatient population of 206 diabetic and 101 non-diabetic subjects, of whom 50% with clinically manifest CVD, undergoing to an extensive clinical, biochemical, and vascular phenotype characterization. RESULTS: The major characteristics of ED (tertile 1 vs 3), in addition to lower post-ischemic vasodilatory reserve (34 vs 203%), were a 3-fold higher baseline pulse amplitude and a delayed (60 second) peak response. The main determinant of this response was the baseline pulse amplitude (Stß = -0.59), which in turn was influenced by age (Stß = 0.13), central obesity (Stß = 0.27) and inversely by HDL cholesterol (Stß = -0.17), and systolic blood pressure (Stß = -0.19). No association was observed with cardiovascular risk factors, previous cardiovascular event or extent of atherosclerosis (ABI and IMT, PWV). Most of the variability in baseline pulse amplitude remained unexplained (r(2) = 0.14). CONCLUSIONS: ED, as detected by PAT in a population enriched with subjects at risk for CVD neither reflects the burden of classical risk factors (under treatment) nor the severity of atherosclerosis. Aside from central obesity and HDL cholesterol, most of the factors responsible for this ED remain unknown.
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Aterosclerose/fisiopatologia , Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Manometria , Obesidade/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Lower extremity arterial disease (LEAD) and increased aortic stiffness are associated with higher mortality in patients with chronic coronary syndrome, while their prognostic significance after an acute coronary syndrome (ACS) is less known. METHODS: We analyzed prevalence, clinical phenotypes and association of LEAD - assessed by the ankle-brachial index (ABI) - and increased aortic stiffness - assessed by the aortic pulse wave velocity (PWV) - with all-cause mortality and major adverse cardiovascular events (MACE) in patients admitted with an ACS. RESULTS: Among 270 patients admitted for ACS (mean age 67âyears, 80% males), 41 (15%) had an ABI ≤0.9, with 14 of them (34%) presenting with intermittent claudication (symptomatic LEAD). Patients with symptomatic LEAD, compared with those with asymptomatic LEAD or without LEAD, had higher prevalence of cardiovascular risk factors, lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein. Patients with LEAD, either symptomatic or asymptomatic, more frequently presented with non-ST-elevation myocardial infarction and more frequently had multivessel coronary artery disease. Both symptomatic and asymptomatic LEAD were significantly associated with all-cause mortality after adjustment for confounders, including multivessel disease or carotid artery disease (hazard ratio 4.03, 95% confidence interval 1.61-10.08, Pâ<â0.01), whereas PWV was not associated with the outcome in the univariable model. LEAD and PWV were not associated with a higher risk of MACE (myocardial infarction or unstable angina, stroke, or transient ischemic attack). CONCLUSIONS: LEAD, either clinical or subclinical, but not increased aortic stiffness, is an independent predictor of all-cause mortality in patients admitted for ACS.
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Physical activity (PA) may modify cardiovascular structure and function as well as insulin sensitivity and level of plasma adipokines in relation to its extent, duration, and intensity. To evaluate the associations of average daily PA and bouts of moderate-to-vigorous-intensity PA with cardiovascular and metabolic measures, 45 healthy volunteers (mean age = 42 ± 9 years) not involved in regular intensive exercise training and competitive sport activity underwent the following examinations: (1) accelerometer monitoring of ambulatory movements (average monitoring time = 6.1 ± 1.3 days); (2) complete carotid and cardiac ultrasound; (3) measurement of carotid-femoral pulse-wave velocity; (4) anthropometric measurements; (5) euglycemic hyperinsulinemic clamp; and (6) assessment of plasma levels of leptin, adiponectin, and high-sensitivity C-reactive protein (hsCRP). Average PA measured by accelerometer correlated with carotid beta-stiffness index (inversely) and with longitudinal systolic myocardial velocity (directly), independently of age, anthropometric, hemodynamic, and metabolic parameters. Subjects with periods of moderate-to-vigorous-intensity PA lasting at least 10 min (n = 28) had higher left ventricular (LV) mass index and lower plasma adiponectin, leptin, and hsCRP (P < 0.05 for all) compared with those who spent the monitoring time only in sedentary and light-intensity PA (n = 17). Minutes per day spent in moderate-to-vigorous PA correlated with LV mass index (directly) and with plasma adiponectin (inversely). Plasma adiponectin was an independent determinant of LV mass, together with body surface area, stroke volume, and systolic blood pressure (cumulative r (2) = 0.80). We conclude that in healthy subjects, average daily PA is independently related to longitudinal systolic myocardial function and to local carotid stiffness. Bouts of moderate-to-vigorous PA seem to induce LV mass increase, which may be partially related to a decrease in plasma adiponectin level.
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Adiponectina/sangue , Pressão Sanguínea/fisiologia , Fenômenos Fisiológicos Cardiovasculares , Atividade Motora/fisiologia , Adulto , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48-0.92, p = 0.01), CAC score > 100 (1.59; 1.08-2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19-3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population.
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The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction.
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[This corrects the article DOI: 10.3389/fphys.2022.866045.].
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Background: The arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted 'wave transmission model', the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the 'Windkessel function' of the elastic arteries. Recently, a 'reservoir-excess pressure' model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related 'reservoir' pressure and a wave-related 'excess' pressure. Methods: In this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis. Results: Compared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP. Conclusion: This is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness.
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BACKGROUND: Carotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography. OBJECTIVES: The Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques. STUDY DESIGN: We will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727).
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Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas , Imagem Multimodal , Placa Aterosclerótica/diagnóstico por imagem , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/patologia , Demência Vascular/complicações , Demência Vascular/patologia , Humanos , AVC Isquêmico , Imagem Multimodal/métodos , Placa Aterosclerótica/patologia , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated. METHODS: Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured. RESULTS: After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 µm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP. CONCLUSIONS: Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.
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Artérias Carótidas/fisiologia , Diabetes Mellitus Tipo 1/sangue , Células Endoteliais/metabolismo , Células-Tronco/metabolismo , Rigidez Vascular/fisiologia , Adolescente , Fatores Etários , Artérias Carótidas/patologia , Estudos de Coortes , Diabetes Mellitus Tipo 1/patologia , Células Endoteliais/patologia , Feminino , Humanos , Masculino , Células-Tronco/patologia , Adulto JovemRESUMO
AIMS: This study investigated whether sedentary behaviour and different activity levels have an independent association with carotid intima-media thickness (IMT) and with the 3-year IMT progression in different carotid segments. METHODS AND RESULTS: The study population included 614 healthy men and women (mean age = 44 +/- 8 years) without carotid atherosclerosis and without increased coronary heart disease risk, who underwent B-mode carotid ultrasound and objective physical activity assessment by accelerometer (mean monitoring time = 5.7 +/- 1.5 days). Time spent in sedentary (57.6 +/- 9.1%), light (41.0 +/- 9.2%), moderate and vigorous activities was determined. Sedentary behaviour was expressed as the ratio of time spent in sedentary and light activity (sedentary/light ratio) as these two activities occupied the majority of waking time. In 495 subjects, the carotid ultrasound was repeated 3 years after the baseline examination. After adjustment for age and the established risk factors that were independent determinants of carotid wall thickness in our population, sedentary/light ratio was independently associated only with the common carotid artery (CCA) IMT. The 3-year increase in CCA IMT was significantly lower in subjects with periods of vigorous activity (7 +/- 40 microm) when compared with those with light activity only or with periods of moderate activity (22 +/- 51 and 19 +/- 46 microm, respectively, P < 0.05). CONCLUSION: The healthy, young-to-middle age population of this study spent more than half of their waking time in sedentary activities. The proportion of time spent in sedentary activities was directly associated with baseline CCA IMT, independently of age and established atherosclerotic risk factors. In the longitudinal analysis, period of vigorous activity influenced the 3-year IMT progression in CCA.
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Artéria Carótida Primitiva/anatomia & histologia , Exercício Físico/fisiologia , Comportamento Sedentário , Adulto , Composição Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Túnica Íntima/anatomia & histologia , Túnica Média/anatomia & histologiaRESUMO
Pulse wave velocity (PWV) is a powerful predictor of cardiovascular events. However, its intrinsic blood pressure (BP)-dependency complicates distinguishing between acute and chronic effects of increased BP on arterial stiffness. Based on the assumption that arteries exhibit a nearly exponential pressure-area (P-A) relationship, this study proposes a method to assess intersubject differences in local PWV independently from BP. The method was then used to analyze differences in local carotid PWV (cPWV) between hypertensive and healthy normotensive people before and after BP-normalization. Pressure (P) and diameter (D) waveforms were simultaneously acquired via tonometer at the left and ultrasound scanning at right common carotid artery (CCA), respectively, in 22 patients with Grade 1 or 2 hypertension and 22 age- and sex-matched controls. cPWV was determined using the D 2 P-loop method. Then, the exponential modeling of the P-area (A = πD 2/4) relationships allowed defining a mathematical formulation to compute subject-specific changes in cPWV associated with BP changes, thus enabling the normalization of cPWV against intersubject differences in BP at the time of measurement. Carotid systolic BP (SBP) and diastolic BP (DBP) were, on average, 17.7 (p < 0.001) and 8.9 mmHg (p < 0.01) higher in hypertensives than controls, respectively. cPWV was 5.56 ± 0.86 m/s in controls and 6.24 ± 1.22 m/s in hypertensives. BP alone accounted for 68% of the cPWV difference between the two groups: 5.80 ± 0.84 vs. 6.03 ± 1.07 m/s after BP-normalization (p = 0.47). The mechanistic normalization of cPWV was in agreement with that estimated by analysis of covariance (ANCOVA). In conclusion, the proposed method, which could be easily implemented in the clinical setting, allows to assess the intersubject differences in PWV independently of BP. Our results suggested that mild hypertension in middle-aged subjects without target organ damage does not significantly alter the stiffness of the CCA wall independently of acute differences in BP. The results warrant further clinical investigations to establish the potential clinical utility of the method.
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Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and <0.05). In the view of previous evidence linking plasma GGT concentration to the level of systemic oxidative stress, our findings suggest a role of oxidative stress in subclinical arterial damage and in prehypertension, even in healthy subjects free of cardiometabolic risk. Arterial organ damage may represent the link between GGT and hypertension.
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Hipertensão , Pré-Hipertensão , Pressão Sanguínea , Espessura Intima-Media Carotídea , Humanos , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/epidemiologia , Fatores de Risco , gama-GlutamiltransferaseRESUMO
The estimation of central aortic blood pressure is a cardinal measurement, carrying effective physiological, and prognostic data beyond routine peripheral blood pressure. Transfer function-based devices effectively estimate aortic systolic and diastolic blood pressure from peripheral pressure waveforms, but the reconstructed pressure waveform seems to preserve features of the peripheral waveform. We sought to develop a new method for converting the local diameter distension waveform into a pressure waveform, through an exponential function whose parameters depend on the local wave speed. The proposed method was then tested at the common carotid artery. Diameter and blood velocity waveforms were acquired via ultrasound at the right common carotid artery while simultaneously recording pressure at the left common carotid artery via tonometer in 203 people (122 men, 50 ± 18 years). The wave speed was noninvasively estimated via the lnDU-loop method and then used to define the exponential function to convert the diameter into pressure. Noninvasive systolic and mean pressures estimated by the new technique were 3.8 ± 21.8 (p = 0.015) and 2.3 ± 9.6 mmHg (p = 0.011) higher than those obtained using tonometery. However, differences were much reduced and not significant in people >35 years (0.6 ± 18.7 and 0.8 ± 8.3 mmHg, respectively). This proof of concept study demonstrated that local wave speed, estimated from noninvasive local measurement of diameter and flow velocity, can be used to determine an exponential function that describes the relationship between local pressure and diameter. This pressure-diameter function can then be used for the noninvasive estimation of local arterial pressure.
Assuntos
Pressão Arterial , Determinação da Pressão Arterial/métodos , Modelos Cardiovasculares , Adolescente , Adulto , Idoso , Determinação da Pressão Arterial/normas , Artérias Carótidas/fisiologia , Circulação Cerebrovascular , Feminino , Humanos , MasculinoRESUMO
OBJECTIVES: Arterial stiffness as pulse wave velocity (PWV) predicts cardiovascular events independently of blood pressure (BP). PWV does not distinguish between stiffness in systole and diastole. This cross-sectional study aimed to test the hypothesis that viscous and elastic carotid wall properties differ between systole and diastole, distinguishing effects of ageing, hypertension and T2 diabetes (T2DM). METHODS: We examined carotid visco-elasticity in 307 people (180 men), with hypertension alone (nâ=â69), combined hypertension/T2DM (H-T2DM, nâ=â99), normotensive (N-T2DM, nâ=â25) and healthy controls (nâ=â114). Diameter (D)/pressure (P) waveforms were measured at right /left common carotid arteries, respectively. Local carotid PWV and distensibility in systole and diastole were evaluated by the D2P-loop method, and wall viscosity from hysteresis, the area (HA) within the P--D loop, as a dynamic measure of systolic loading and diastolic unloading. RESULTS: Controls' hysteresis fell quadratically with age (R2â=â0.23, Pâ<â0.001). Yet mean HA in hypertensive patients (0.95, 95% CI 0.65-1.23) was six-fold higher than in age-matched controls (0.14, -0.20 to 0.49, Pâ<â0.001) with a 2.5× difference between diastolic (dDs) to systolic (sDs) distensibility (Pâ<â0.05) in hypertensive patients. HA was higher in hypertensive patients and H-T2DMs (0.80, 0.58-1.04) than N-T2DMs (0.20, -0.17 to 0.54, Pâ<â0.05), but similar between controls and N-T2DMs. BP-adjusted carotid diameters in all T2DM were significantly greater compared with controls and hypertensive patients. CONCLUSION: Higher BP increased wall viscosity, hysteresis and relative difference between systolic and diastolic distensibility across groups. Carotid diameters were increased in all T2DMs, more in H-T2DM, probably altering BP-flow dynamics in T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Envelhecimento , Pressão Sanguínea , Artérias Carótidas/diagnóstico por imagem , Estudos Transversais , Elasticidade , Humanos , Masculino , Análise de Onda de PulsoRESUMO
PURPOSE: It is unclear whether plasma homocysteine (Hcy) has a direct noxious impact on the cardiovascular (CV) system or whether its association with cardiovascular events (CVEs) is mediated by established risk factors. To explore the role of Hcy in CV impairment, the study evaluated cross-sectional relationships between plasma Hcy and indices of CV organ damage together with the associations of these indices with the history of CVEs. METHODS: In 269 patients with a high prevalence of diabetes, dyslipidemia, and hypertension, the carotid intima-media thickness, ankle-brachial index (ABI), reactive hyperemic index, carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, and cardiac index were measured. RESULTS: 132 patients had carotid plaque, 31 ABIâ <â 0.90, 126 endothelial dysfunction, 66 increased cfPWV, 125 LV hypertrophy (LVH), 153 decreased cardiac index, and 115 a history of CVEs. Plasma Hcy levels were related to LV mass and ABI, after adjustment for covariates and creatinine. Significantly higher Hcy levels were found in patients with LVH (8.5 [4.4] vs 7.6 [2.8] µmol/L; adjusted Pâ =â .001) and ABIâ <â 0.9 (10.4 [3.8] vs 7.9 [3.4] µmol/L; adjusted Pâ =â .001) than in those with LV mass and ABI within limits. Hcy levels were comparable between patients with and without carotid plaques, increased arterial stiffness, impaired endothelial, and LV pump function. Within markers of CV organ damage, only LVH was associated with a history of CVEs. CONCLUSION: This study demonstrated an independent association between Hcy and LV mass as well as between LVH and a history of CVEs and suggests that LVH may represent 1 of the pathophysiologic links between Hcy and CV risk.
Assuntos
Homocisteína/sangue , Hipertrofia Ventricular Esquerda/epidemiologia , Placa Aterosclerótica/epidemiologia , Adulto , Idoso , Índice Tornozelo-Braço , Biomarcadores/sangue , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Dislipidemias/sangue , Dislipidemias/epidemiologia , Ecocardiografia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Prevalência , Análise de Onda de Pulso , Fatores de Risco , Rigidez VascularRESUMO
INTRODUCTION: The effect of metabolic syndrome (MS) on carotid stiffness (CS) in the context of gender is under research. OBJECTIVE: We examined the relationship between the MS and CS in men (M) and women (W) and investigated if the impact of cardiovascular risk factors on CS is modulated by gender. PATIENTS AND METHODS: The study included 419 subjects (mean age 54.3 years): 215 (51%) with MS (109 W and 106 M) and 204 (49%) without MS (98 W and 106 M). Carotid intima-media thickness (IMT) and CS parameters (beta stiffness index (beta), Peterson's elastic modulus (Ep), arterial compliance (AC) and one-point pulse wave velocity (PWV-beta)) were measured with the echo-tracking (eT) system. RESULTS: ANCOVA demonstrated that MS was associated with elevated CS indices (p = 0.003 for beta and 0.025 for PWV-beta), although further sex-specific analysis revealed that this relationship was significant only in W (p = 0.021 for beta). Age was associated with CS in both M and W, pulse pressure (PP) and body mass index turned out to be determinants of CS solely in W, while the effect of mean arterial pressure (MAP) and heart rate was more pronounced in M. MANOVA performed in subjects with MS revealed that age and diabetes mellitus type 2 were determinants of CS in both sexes, diastolic blood pressure and MAP - solely in M and systolic blood pressure, PP and waist circumference - solely in W (the relationship between the waist circumference and AC was paradoxical). CONCLUSION: The relationship between MS and CS is stronger in W than in M. In subjects with MS, various components of arterial pressure exert different sex-specific effects on CS - with the impact of the pulsative component of arterial pressure (PP) observed in W and the impact of the steady component (MAP) observed in M.
RESUMO
PURPOSE: Obesity clearly increases cardiovascular risk, often inducing high blood pressure (BP), impaired left ventricular (LV) function, and increased arterial stiffness. Intensive weight loss and bariatric surgery induce improvement in hypertension and diabetes for morbid obesity. Carotid artery haemodynamics is a powerful prognostic indicator for stroke and cognitive decline independent of BP. The aim of this study was to evaluate the impact of a 3-stage bariatric strategy of diet, bariatric surgery, and consequent weight loss on carotid haemodynamics and cardiac diastolic function. MATERIAL AND METHODS: This prospective study included 26 patients (45 ± 10 years, 4 men) with severe obesity undergoing bariatric surgery without comorbidities (hypertension, diabetes, etc.). Anthropometry, BP, Doppler echocardiography, and common carotid haemodynamics by ultrasound were measured at three times: (1) baseline, (2) after 1-month diet (post-diet), and (3) 8 months after surgery (post-surgery). The lnDU-loop method was used to estimate local carotid pulse wave velocity (ncPWV). RESULTS: Baseline BMI was 47.9 ± 7.1 kg/m2 and reduced by 5% and 30% post-diet and post-surgery, respectively. BP decreased only post-diet, without pulse pressure change. However, ncPWV, 6.27 ± 1.35 m/s at baseline, was significantly reduced by 10% and 23% post-diet and post-surgery, respectively, also adjusted for BP changes. The E/A ratio rose from 0.95 ± 0.20 to 1.27 ± 0.31 (p < 0.005), without change in LV geometry or mass, while heart rate and cardiac output fell substantially. CONCLUSION: Weight loss following diet and bariatric surgery is associated with reduced carotid arterial stiffness and improved LV diastolic function. Diet and bariatric surgery are effective treatments for morbid obesity with its concomitant adverse cardiovascular effects.