Background: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk ... more Background: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. Methods: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. Results: Subjects were 64±11 years (range 40–89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the...
BackgroundThe arterial pressure waveform reflects the interaction between the heart and the arter... more BackgroundThe 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.MethodsIn this study we applied the reservoir-excess pressure approach...
2018 Computing in Cardiology Conference (CinC), 2018
Background: Stiffened arteries represent a major cardiovascular risk. Aim: We describe a vendor i... more Background: Stiffened arteries represent a major cardiovascular risk. Aim: We describe a vendor independent software for the non-invasive determination of arterial stiffness using ultrasound images. Methods: We have developed an intensity-based semiautomatic software for determining the edges of the luminal arterial walls (M-mode) and blood velocity (PW Doppler) to extract diameter and velocity waveform from ultrasound images. The upstroke of the two waveforms is automatically determined as well as the fit of the initial linear portion of the ln(D)U-loop. Pulse wave velocity (PWV), which is proportional to the slope of ln(D)U-loop during early systole is calculated as a measure of arterial stiffness. The user can over-ride and correct the automatically determined parameters if necessary. Results: A semi-automatic code was developed for tracing the luminal diameter and blood velocity in the human ascending aorta. D and U waveforms were extracted and used in ln(D)U-loops to calculate ...
Background Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide... more Background Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, even among young adults. This condition shares many risk factors with other metabolic disorders, including cardiovascular disease (CVD), but researchers suggest the presence of NAFLD itself may be a risk factor for developing CVD, independently of other established factors. Methods In this prospective, general population-based cohort study of young adults in the UK, transient elastography-defined liver steatosis and fibrosis were assessed at age 24 years, as were cardiovascular structure and function, measured using echocardiography, carotid ultrasonography and pulse wave analysis. We examined associations between liver and cardiovascular health, with and without accounting for age, sex, ethnicity, social class, employment, body mass index, alcohol, smoking, blood pressure, fasting serum lipids, fasting glucose, fasting insulin and C-reactive protein. All participants with harmful alco...
Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (C... more Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disea...
Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired... more Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired organ and tissue perfusion. Relief of aortic stenosis by transcatheter aortic valve replacement (TAVR) is associated with both a short- and long-term hypertensive response. Counterintuitively, patients who are long-term normotensive post-TAVR have a worsened prognosis compared with patients with hypertension, yet the underlying mechanisms are not understood. We investigated immediate changes in invasively measured left ventricular and central aortic pressure post-TAVR in patients with severe aortic stenosis using aortic reservoir pressure, wave intensity analysis, and indices of aortic function. Fifty-four patients (mean age 83.6±6.2 years, 50.0% female) undergoing TAVR were included. We performed reservoir pressure and wave intensity analysis on invasively acquired pressure waveforms from the ascending aorta and left ventricle immediately pre- and post-TAVR. Following TAVR, there were ...
Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular dis... more Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HD...
Accurate measurement of blood pressure (BP) is crucial for hypertension management. Accuracy of b... more Accurate measurement of blood pressure (BP) is crucial for hypertension management. Accuracy of brachial cuff (BCUFF) devices to measure invasive (intra-arterial) BP at the brachial artery (BINV) and aorta (AINV) has never been systematically assessed. This study aimed to determine the: 1) relationship between BINV and AINV; 2) accuracy of BCUFF devices to estimate invasive BP and; 3) accuracy of BCUFF devices to classify BP thresholds. Three individual patient meta-analyses (by search of online databases and systematic review supplemented by measurements in a tertiary hospital cardiac catheterization laboratory) were performed to determine: 1) BINV versus AINV BP; 2) BCUFF versus BINV BP and AINV BP and; 3) BCUFF for BP classification versus invasive BP. Most subjects (90%) were patients undergoing cardiac catheterization (total N = 3004; mean age 58.7 years, 95%CI [54.0, 63.4], 68% male). As shown in the table: 1) BINV systolic BP (SBP) was significantly higher than AINV SBP whils...
It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes M... more It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p=0.008). T2DM was associated with greater arteriolar diameter (p=0.03) and optimality ratio (p=0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p=0.03). The inclusion of retinal measu...
Background: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk ... more Background: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. Methods: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. Results: Subjects were 64±11 years (range 40–89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the...
BackgroundThe arterial pressure waveform reflects the interaction between the heart and the arter... more BackgroundThe 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.MethodsIn this study we applied the reservoir-excess pressure approach...
2018 Computing in Cardiology Conference (CinC), 2018
Background: Stiffened arteries represent a major cardiovascular risk. Aim: We describe a vendor i... more Background: Stiffened arteries represent a major cardiovascular risk. Aim: We describe a vendor independent software for the non-invasive determination of arterial stiffness using ultrasound images. Methods: We have developed an intensity-based semiautomatic software for determining the edges of the luminal arterial walls (M-mode) and blood velocity (PW Doppler) to extract diameter and velocity waveform from ultrasound images. The upstroke of the two waveforms is automatically determined as well as the fit of the initial linear portion of the ln(D)U-loop. Pulse wave velocity (PWV), which is proportional to the slope of ln(D)U-loop during early systole is calculated as a measure of arterial stiffness. The user can over-ride and correct the automatically determined parameters if necessary. Results: A semi-automatic code was developed for tracing the luminal diameter and blood velocity in the human ascending aorta. D and U waveforms were extracted and used in ln(D)U-loops to calculate ...
Background Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide... more Background Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, even among young adults. This condition shares many risk factors with other metabolic disorders, including cardiovascular disease (CVD), but researchers suggest the presence of NAFLD itself may be a risk factor for developing CVD, independently of other established factors. Methods In this prospective, general population-based cohort study of young adults in the UK, transient elastography-defined liver steatosis and fibrosis were assessed at age 24 years, as were cardiovascular structure and function, measured using echocardiography, carotid ultrasonography and pulse wave analysis. We examined associations between liver and cardiovascular health, with and without accounting for age, sex, ethnicity, social class, employment, body mass index, alcohol, smoking, blood pressure, fasting serum lipids, fasting glucose, fasting insulin and C-reactive protein. All participants with harmful alco...
Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (C... more Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disea...
Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired... more Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired organ and tissue perfusion. Relief of aortic stenosis by transcatheter aortic valve replacement (TAVR) is associated with both a short- and long-term hypertensive response. Counterintuitively, patients who are long-term normotensive post-TAVR have a worsened prognosis compared with patients with hypertension, yet the underlying mechanisms are not understood. We investigated immediate changes in invasively measured left ventricular and central aortic pressure post-TAVR in patients with severe aortic stenosis using aortic reservoir pressure, wave intensity analysis, and indices of aortic function. Fifty-four patients (mean age 83.6±6.2 years, 50.0% female) undergoing TAVR were included. We performed reservoir pressure and wave intensity analysis on invasively acquired pressure waveforms from the ascending aorta and left ventricle immediately pre- and post-TAVR. Following TAVR, there were ...
Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular dis... more Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HD...
Accurate measurement of blood pressure (BP) is crucial for hypertension management. Accuracy of b... more Accurate measurement of blood pressure (BP) is crucial for hypertension management. Accuracy of brachial cuff (BCUFF) devices to measure invasive (intra-arterial) BP at the brachial artery (BINV) and aorta (AINV) has never been systematically assessed. This study aimed to determine the: 1) relationship between BINV and AINV; 2) accuracy of BCUFF devices to estimate invasive BP and; 3) accuracy of BCUFF devices to classify BP thresholds. Three individual patient meta-analyses (by search of online databases and systematic review supplemented by measurements in a tertiary hospital cardiac catheterization laboratory) were performed to determine: 1) BINV versus AINV BP; 2) BCUFF versus BINV BP and AINV BP and; 3) BCUFF for BP classification versus invasive BP. Most subjects (90%) were patients undergoing cardiac catheterization (total N = 3004; mean age 58.7 years, 95%CI [54.0, 63.4], 68% male). As shown in the table: 1) BINV systolic BP (SBP) was significantly higher than AINV SBP whils...
It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes M... more It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p=0.008). T2DM was associated with greater arteriolar diameter (p=0.03) and optimality ratio (p=0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p=0.03). The inclusion of retinal measu...
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Papers by Alun Hughes