Background: Whether earlier onset of puberty is associated with higher cardiovascular risk in ear... more Background: Whether earlier onset of puberty is associated with higher cardiovascular risk in early adulthood is not well understood. Our objective was to examine the association between puberty timing and markers of cardiovascular structure and function at age 25 years. Methods: We conducted a prospective birth cohort study using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were born between April 1, 1991, and December 31, 1992. Exposure of interest was age at peak height velocity (aPHV), an objective and validated growth-based measure of puberty onset. Outcome measures included cardiovascular structure and function at age 25 years: carotid intima-media thickness (CIMT), left ventricular mass index (LVMI) and relative wall thickness (RWT), pulse wave velocity (PWV) and systolic blood pressure (SBP). Multiple imputation was used to impute missing data on covariates and outcomes. Linear regression was used to examine the association between aPHV and each measure of cardiac structure and function, adjusting for maternal age, gestational age, household social class, maternal education, mother's partner's education, breastfeeding, parity, birthweight, maternal body mass index, maternal marital status, maternal prenatal smoking status and height and fat mass at age 9. All analyses were stratified by sex. Results: A total of 2752-4571 participants were included in the imputed analyses. A 1-year older aPHV was not strongly associated with markers of cardiac structure and function in males and females at 25 years and most results spanned the null value. In adjusted analyses, a 1-year older aPHV was associated with 0.003 mm (95% confidence interval (CI) 0.00001, 0.006) and 0.0008 mm (95% CI − 0.002, 0.003) higher CIMT; 0.02 m/s (95% CI − 0.05, 0.09) and 0.02 m/s (95% CI − 0.04, 0.09) higher PWV; and 0.003 mmHg (95% CI − 0.60, 0.60) and 0.13 mmHg (95% CI − 0.44, 0.70) higher SBP, among males and females, respectively. A 1-year older aPHV was associated with − 0.55 g/m 2.7 (95% CI − 0.03, − 1.08) and − 0.89 g/m 2.7 (95% CI − 0.45, − 1.34) lower LVMI and − 0.001 (95% CI − 0.006, 0.002) and − 0.002 (95% CI − 0.006, 0.002) lower RWT among males and females. Conclusions: Earlier puberty is unlikely to have a major impact on pre-clinical cardiovascular risk in early adulthood.
Conclusion CRT was associated with improvement in all echocardiographic parameters, including LVE... more Conclusion CRT was associated with improvement in all echocardiographic parameters, including LVEF, reduction in LV volumes, and NYHA class. The findings are limited by the small sample size, short follow-up, and absence of a control group.
men with T2D had increased LV concentricity, systolic, and diastolic dysfunction. MPR was signifi... more men with T2D had increased LV concentricity, systolic, and diastolic dysfunction. MPR was significantly lower in T2D than controls (2.9±0.9 vs 3.5±1.1, p<0.001) and lower in diabetic women than men (2.7±0.9 vs 3.0±0.9, p<0.001). A greater proportion of women with T2D had MPR of <2.5 (45% vs 28%, p<0.001). In a regression model adjusting for clinical risk factors, only age (b=-0.184, p=0.004), female sex (b=-0.210, p<0.001) and systolic blood pressure (SBP) (b=-0.119, p=0.021) were independently associated with MPR in T2D. Sex-stratified analysis showed independent associations with MPR: age (b=-0.221, p=0.022), SBP (b=-0.122, p=0.131), and BMI (b =-0.188, p=0.026) in women, and age (b=-0.150, p=0.085) and SBP (b=-0.155, p=0.027) in men. Imaging measures of LV concentricity, filling pressure, and diffuse fibrosis did not independently predict MPR in T2D. Discussion In adults without cardiovascular disease, women who developed T2D had a greater reduction in MPR compared to men. This is associated with traditional risk factors but not subclinical cardiac remodelling. Early interventions focussed on blood pressure reduction and weight loss, may prevent coronary microvascular dysfunction. Conclusion Age and systolic blood pressure are independent predictors of MPR in people with T2D. BMI is an additional independent risk factor for MPR in women but not men. Acknowledgements Funding was provided by a NIHR research professorship award (RP2017-08-ST2-007), NIHR career development fellowship (CDF 2014-07-045), a BHF Clinical Research Training Fellowship (FS/16/47/32190), the Medical Research Council (MRC) and Novo Nordisk. REFERENCE 1. Ohkuma T, Komorita Y, Peters SAE, et al. Diabetes as a risk factor for heart failure in women and men: a systematic review and metaanalysis of 47 cohorts including 12 million individuals.
Background Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increa... more Background Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins. Methods Nuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR). Results The majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk; often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimer's disease (AD: HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM: VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD: LDL-C, IDL-C). Conclusions The cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention.
Scandinavian Journal of Medicine & Science in Sports, May 8, 2021
Objective. Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factor... more Objective. Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness and the acute BP response to exercise in a large birth cohort of adolescents. Methods. 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8±0.4 years, 38.5% male) completed a submaximal exercise step-test that allowed fitness (VO 2 max) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. Results. Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, Accepted Article This article is protected by copyright. All rights reserved height, smoking and socioeconomic status (standardized β:-1.80, 95%CI:-2.64,-0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD). Conclusion. Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitnessexercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realised with more-favourable body composition.
Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height 2.... more Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height 2.7 (LVMi 2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi 2.7 ; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi 2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment.
A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is ... more A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is unknown whether the health deficit burden is related to the appearance of cardiovascular disease. In order to answer this question, the same multidimensional FI looking at 45-health deficits was serially calculated per participant at 4 time periods (0-16, 19-44, 45-54 and 60-64 years) using data from the 1946 Medical Research Council (MRC) British National Survey of Health and Development (NSHD)the world's longest running longitudinal birth cohort with continuous follow-up. From these the mean and total FI for the life-course, and the step change in deficit accumulation from one time period to another was derived. Echocardiographic data at 60-64 years provided: ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCF i) and E/e′. Generalized linear models assessed the association between FIs and echocardiographic parameters after adjustment for relevant covariates. 1375 participants were included. For each single new deficit accumulated at any one of the 4 time periods, LVmass i increased by 0.91-1.44% (p < 0.013), while MCF i decreased by 0.6-1.02% (p < 0.05). A unit increase in FI at age 45-54 and 60-64, decreased EF by 11-12% (p < 0.013). A single health deficit step change occurring between 60 and 64 years and one of the earlier time periods, translated into higher odds (2.1-78.5, p < 0.020) of elevated LV filling pressure. Thus, the accumulation of health deficits at any time period of the life-course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function. Cardiovascular diseases (CVDs) are the leading cause of death in the developed world and the second cause of mortality (after infectious diseases) in the developing world accounting for more than 30% of all global deaths 1. The current knowledge base for the development of CVDs revolves mostly around traditional risk factors such as hypertension and diabetes. As such, there has been a research call for exploring novel risk factors 2. Given the recent medical advancements, previously deadly diseases became chronic manageable conditions. Thus, as people age, they tend to accumulate an increasing number of health deficits. However, accumulating health deficits predisposes to further deficit accumulation and premature death 3. A frailty index quantifies the accumulated health deficits 4 and can be appraised in either of three ways: (1) the rules-based operational definition relies on a set of phenotypical rules of performance against which the individual is scored 5 ; (2) the clinical frailty score grades persons along a spectrum from very fit to very frail based on clinical judgment; and (3) the frailty index (FI) counts health deficit accumulation as the ratio between the number of deficits present, and the total number of deficits appraised, with sub-unitary scores for partial deficits 6. The FI is most widely used in research because it is easy to score, can accommodate partial deficits, correlates with the clinical frailty score 3 , has been extensively validated and shown to predict mortality 7 and other negative health outcomes 8. The FI of accumulated health deficits should not be confused with a physical frailty phenotypic score that only appraises domains such as shrinking, exhaustion, low physical activity, slow gait speed and weak grip strength.
Background In the UK, previous work suggests ethnic inequalities in hypertension management. We s... more Background In the UK, previous work suggests ethnic inequalities in hypertension management. We studied ethnic differences in hypertension management and their contribution to blood pressure (BP) control. Methods We conducted a cohort study of antihypertensive-naïve individuals of European, South Asian and African/ African Caribbean ethnicity with a new raised BP reading in UK primary care from 2006 to 2019, using the Clinical Practice Research Datalink (CPRD). We studied differences in: BP re-measurement after an initial hypertensive BP, antihypertensive initiation, BP monitoring, antihypertensive intensification, antihypertensive persistence/adherence and BP control one year after antihypertensive initiation. Models adjusted for socio-demographics, BP, comorbidity, healthcare usage and polypharmacy (plus antihypertensive class, BP monitoring, intensification, persistence and adherence for BP control models).
ABSTRACTObjectiveLow-grade inflammation in the young may contribute to the early development of a... more ABSTRACTObjectiveLow-grade inflammation in the young may contribute to the early development of adverse cardiometabolic risk profiles. We assessed whether measures of glycoprotein acetylation (GlycA) were better able to detect the development of these changes compared to the more commonly used biomarker high-sensitivity C-reactive protein (CRP), and investigated whether these relationships differed in an adolescent compared to young adult cohort.Research Design and MethodsA total of 3306 adolescents (Avon Longitudinal Study of Parents and Children - ALSPAC; mean age 15.4±0.3; n=1750) and young adults (Cardiovascular Risk in Young Finns Study - YFS; mean age 32.1±5.0; n=1556) were included. Inflammatory biomarkers (GlycA/CRP), body composition (BMI / waist circumference) and cardiometabolic risk factors (blood pressure, triglycerides, HDL-c, glucose, insulin, and homeostasis model of insulin resistance [HOMA_IR]), were measured at baseline and again in 9-10 year follow-up. Metabolic ...
Background: 3D speckle-tracking echocardiography (3D-STE) is a novel method to quantify left vent... more Background: 3D speckle-tracking echocardiography (3D-STE) is a novel method to quantify left ventricular (LV) mechanical dyssynchrony. 3D-STE is influenced by image quality, but studies on the magnitude of its effect on 3D-STE derived LV systolic dyssynchrony indices (SDIs) and their test-retest reproducibility are limited. Methods: 3D-STE was performed in two groups, each comprising 18 healthy volunteers with good echocardiographic windows. In study 1, optimal and inferior-quality images, by intentionally poor echocardiographic technique, were acquired. In study 2, sub-optimal quality images were acquired by impairing ultrasound propagation using neoprene rubber sheets (thickness 2, 3, and 4 mm) mimicking mildly, moderately, and severely impaired images, respectively. Measures (normalized to cardiac cycle duration) were volume-and strain-based SDIs defined as the standard deviation of time to minimum segmental values, and volume-and strain-derived dispersion indices. For both studies test-retest reproducibility was assessed. Results: Test-retest reproducibility was better for most indices when restricting the analysis to good quality images; nevertheless, only volume-, circumferential strain-, and principal tangential strain-derived LV dyssynchrony indices achieved fair to good reliability. There was no evidence of systematic bias due to sub-optimal quality image. Volume-, circumferential strain-, and principal tangential strain-derived SDIs correlated closely. Radial strain-and longitudinal strain-SDI correlated moderately or weakly with volume-SDI, respectively. Conclusions: Sub-optimal image quality compromised the reliability of 3D-STE derived dyssynchrony indices but did not introduce systematic bias in healthy individuals. Even with optimal quality images, only 3D-STE indices based on volume, circumferential strain and principal tangential strain showed acceptable test-retest reliability.
BACKGROUND AND PURPOSE Hypoxia causes vasodilatation of coronary arteries, but the underlying mec... more BACKGROUND AND PURPOSE Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca 2+ concentration ([Ca 2+ ]i) by opening of K channels and release of H2S. EXPERIMENTAL APPROACH Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca 2+ ]i, and the expression of voltage-gated K channels KV7 channels (encoded by KCNQ genes) and large-conductance calcium-activated K channels (KCa1.1) was examined. Voltage clamp assessed the role of KV7 channels in hypoxia. KEY RESULTS Gradual reduction of oxygen concentration from 95 to 1% dilated the precontracted coronary arteries and this was associated with reduced [Ca 2+ ]i in PGF2α (10 μM)-contracted arteries whereas no fall in [Ca 2+ ]i was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and KCa1.1 inhibited hypoxia-induced dilatation in PGF2α-contracted arteries; this inhibition was more marked in the presence of the Kv7 channel blockers, XE991 and linopirdine, while a KV7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H2S-and adenosine-induced vasodilatation. PCR revealed the expression of KV7.1, KV7.4, KV7.5 and KCa1.1 channels, and KCa1.1, KV7.4 and KV7.5 were also identified by immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more marked in hypoxic conditions. CONCLUSION The KV7.4 and KV7.5 channels, which we identified in the coronary arteries, appear to have a major role in hypoxia-induced vasodilatation. The voltage clamp results further support the involvement of KV7 channels in this vasodilatation. Activation of these KV7 channels may be induced by H2S and adenosine.
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...
Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in ... more Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status. Methods: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. Results: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (−0.012 mm, 95% CI −0.
weight after 1 year, and 24.1 kg more after 2 years, than the 7,124 lifestyle modification patien... more weight after 1 year, and 24.1 kg more after 2 years, than the 7,124 lifestyle modification patients. On average, surgery led to a 3.2 (95% confidence interval 1.4 to 5.0) mmHg lower systolic blood pressure at year 1 and 3.5 (0.8 to 6.1) mmHg lower systolic blood pressure at year 2, in weighted analyses. Each 10 kg weight loss on average lead to a 2.1 (1.8 to 2.3) mmHg lower systolic blood pressure. Losing weight by surgery lead to a 1.1 (0.0 to 2.1) mmHg smaller blood pressure reduction than losing the same amount of weight by lifestyle treatment. Conclusion: Bariatric surgery lead to substantially greater weight loss and blood pressure reduction compared to intensive lifestyle modification, in this study of two large nationwide registries. The weight loss method per se had a small effect on blood pressure.
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 ...
Background: Whether earlier onset of puberty is associated with higher cardiovascular risk in ear... more Background: Whether earlier onset of puberty is associated with higher cardiovascular risk in early adulthood is not well understood. Our objective was to examine the association between puberty timing and markers of cardiovascular structure and function at age 25 years. Methods: We conducted a prospective birth cohort study using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were born between April 1, 1991, and December 31, 1992. Exposure of interest was age at peak height velocity (aPHV), an objective and validated growth-based measure of puberty onset. Outcome measures included cardiovascular structure and function at age 25 years: carotid intima-media thickness (CIMT), left ventricular mass index (LVMI) and relative wall thickness (RWT), pulse wave velocity (PWV) and systolic blood pressure (SBP). Multiple imputation was used to impute missing data on covariates and outcomes. Linear regression was used to examine the association between aPHV and each measure of cardiac structure and function, adjusting for maternal age, gestational age, household social class, maternal education, mother's partner's education, breastfeeding, parity, birthweight, maternal body mass index, maternal marital status, maternal prenatal smoking status and height and fat mass at age 9. All analyses were stratified by sex. Results: A total of 2752-4571 participants were included in the imputed analyses. A 1-year older aPHV was not strongly associated with markers of cardiac structure and function in males and females at 25 years and most results spanned the null value. In adjusted analyses, a 1-year older aPHV was associated with 0.003 mm (95% confidence interval (CI) 0.00001, 0.006) and 0.0008 mm (95% CI − 0.002, 0.003) higher CIMT; 0.02 m/s (95% CI − 0.05, 0.09) and 0.02 m/s (95% CI − 0.04, 0.09) higher PWV; and 0.003 mmHg (95% CI − 0.60, 0.60) and 0.13 mmHg (95% CI − 0.44, 0.70) higher SBP, among males and females, respectively. A 1-year older aPHV was associated with − 0.55 g/m 2.7 (95% CI − 0.03, − 1.08) and − 0.89 g/m 2.7 (95% CI − 0.45, − 1.34) lower LVMI and − 0.001 (95% CI − 0.006, 0.002) and − 0.002 (95% CI − 0.006, 0.002) lower RWT among males and females. Conclusions: Earlier puberty is unlikely to have a major impact on pre-clinical cardiovascular risk in early adulthood.
Conclusion CRT was associated with improvement in all echocardiographic parameters, including LVE... more Conclusion CRT was associated with improvement in all echocardiographic parameters, including LVEF, reduction in LV volumes, and NYHA class. The findings are limited by the small sample size, short follow-up, and absence of a control group.
men with T2D had increased LV concentricity, systolic, and diastolic dysfunction. MPR was signifi... more men with T2D had increased LV concentricity, systolic, and diastolic dysfunction. MPR was significantly lower in T2D than controls (2.9±0.9 vs 3.5±1.1, p<0.001) and lower in diabetic women than men (2.7±0.9 vs 3.0±0.9, p<0.001). A greater proportion of women with T2D had MPR of <2.5 (45% vs 28%, p<0.001). In a regression model adjusting for clinical risk factors, only age (b=-0.184, p=0.004), female sex (b=-0.210, p<0.001) and systolic blood pressure (SBP) (b=-0.119, p=0.021) were independently associated with MPR in T2D. Sex-stratified analysis showed independent associations with MPR: age (b=-0.221, p=0.022), SBP (b=-0.122, p=0.131), and BMI (b =-0.188, p=0.026) in women, and age (b=-0.150, p=0.085) and SBP (b=-0.155, p=0.027) in men. Imaging measures of LV concentricity, filling pressure, and diffuse fibrosis did not independently predict MPR in T2D. Discussion In adults without cardiovascular disease, women who developed T2D had a greater reduction in MPR compared to men. This is associated with traditional risk factors but not subclinical cardiac remodelling. Early interventions focussed on blood pressure reduction and weight loss, may prevent coronary microvascular dysfunction. Conclusion Age and systolic blood pressure are independent predictors of MPR in people with T2D. BMI is an additional independent risk factor for MPR in women but not men. Acknowledgements Funding was provided by a NIHR research professorship award (RP2017-08-ST2-007), NIHR career development fellowship (CDF 2014-07-045), a BHF Clinical Research Training Fellowship (FS/16/47/32190), the Medical Research Council (MRC) and Novo Nordisk. REFERENCE 1. Ohkuma T, Komorita Y, Peters SAE, et al. Diabetes as a risk factor for heart failure in women and men: a systematic review and metaanalysis of 47 cohorts including 12 million individuals.
Background Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increa... more Background Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins. Methods Nuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR). Results The majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk; often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimer's disease (AD: HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM: VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD: LDL-C, IDL-C). Conclusions The cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention.
Scandinavian Journal of Medicine & Science in Sports, May 8, 2021
Objective. Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factor... more Objective. Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness and the acute BP response to exercise in a large birth cohort of adolescents. Methods. 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8±0.4 years, 38.5% male) completed a submaximal exercise step-test that allowed fitness (VO 2 max) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. Results. Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, Accepted Article This article is protected by copyright. All rights reserved height, smoking and socioeconomic status (standardized β:-1.80, 95%CI:-2.64,-0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD). Conclusion. Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitnessexercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realised with more-favourable body composition.
Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height 2.... more Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height 2.7 (LVMi 2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi 2.7 ; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi 2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment.
A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is ... more A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is unknown whether the health deficit burden is related to the appearance of cardiovascular disease. In order to answer this question, the same multidimensional FI looking at 45-health deficits was serially calculated per participant at 4 time periods (0-16, 19-44, 45-54 and 60-64 years) using data from the 1946 Medical Research Council (MRC) British National Survey of Health and Development (NSHD)the world's longest running longitudinal birth cohort with continuous follow-up. From these the mean and total FI for the life-course, and the step change in deficit accumulation from one time period to another was derived. Echocardiographic data at 60-64 years provided: ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCF i) and E/e′. Generalized linear models assessed the association between FIs and echocardiographic parameters after adjustment for relevant covariates. 1375 participants were included. For each single new deficit accumulated at any one of the 4 time periods, LVmass i increased by 0.91-1.44% (p < 0.013), while MCF i decreased by 0.6-1.02% (p < 0.05). A unit increase in FI at age 45-54 and 60-64, decreased EF by 11-12% (p < 0.013). A single health deficit step change occurring between 60 and 64 years and one of the earlier time periods, translated into higher odds (2.1-78.5, p < 0.020) of elevated LV filling pressure. Thus, the accumulation of health deficits at any time period of the life-course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function. Cardiovascular diseases (CVDs) are the leading cause of death in the developed world and the second cause of mortality (after infectious diseases) in the developing world accounting for more than 30% of all global deaths 1. The current knowledge base for the development of CVDs revolves mostly around traditional risk factors such as hypertension and diabetes. As such, there has been a research call for exploring novel risk factors 2. Given the recent medical advancements, previously deadly diseases became chronic manageable conditions. Thus, as people age, they tend to accumulate an increasing number of health deficits. However, accumulating health deficits predisposes to further deficit accumulation and premature death 3. A frailty index quantifies the accumulated health deficits 4 and can be appraised in either of three ways: (1) the rules-based operational definition relies on a set of phenotypical rules of performance against which the individual is scored 5 ; (2) the clinical frailty score grades persons along a spectrum from very fit to very frail based on clinical judgment; and (3) the frailty index (FI) counts health deficit accumulation as the ratio between the number of deficits present, and the total number of deficits appraised, with sub-unitary scores for partial deficits 6. The FI is most widely used in research because it is easy to score, can accommodate partial deficits, correlates with the clinical frailty score 3 , has been extensively validated and shown to predict mortality 7 and other negative health outcomes 8. The FI of accumulated health deficits should not be confused with a physical frailty phenotypic score that only appraises domains such as shrinking, exhaustion, low physical activity, slow gait speed and weak grip strength.
Background In the UK, previous work suggests ethnic inequalities in hypertension management. We s... more Background In the UK, previous work suggests ethnic inequalities in hypertension management. We studied ethnic differences in hypertension management and their contribution to blood pressure (BP) control. Methods We conducted a cohort study of antihypertensive-naïve individuals of European, South Asian and African/ African Caribbean ethnicity with a new raised BP reading in UK primary care from 2006 to 2019, using the Clinical Practice Research Datalink (CPRD). We studied differences in: BP re-measurement after an initial hypertensive BP, antihypertensive initiation, BP monitoring, antihypertensive intensification, antihypertensive persistence/adherence and BP control one year after antihypertensive initiation. Models adjusted for socio-demographics, BP, comorbidity, healthcare usage and polypharmacy (plus antihypertensive class, BP monitoring, intensification, persistence and adherence for BP control models).
ABSTRACTObjectiveLow-grade inflammation in the young may contribute to the early development of a... more ABSTRACTObjectiveLow-grade inflammation in the young may contribute to the early development of adverse cardiometabolic risk profiles. We assessed whether measures of glycoprotein acetylation (GlycA) were better able to detect the development of these changes compared to the more commonly used biomarker high-sensitivity C-reactive protein (CRP), and investigated whether these relationships differed in an adolescent compared to young adult cohort.Research Design and MethodsA total of 3306 adolescents (Avon Longitudinal Study of Parents and Children - ALSPAC; mean age 15.4±0.3; n=1750) and young adults (Cardiovascular Risk in Young Finns Study - YFS; mean age 32.1±5.0; n=1556) were included. Inflammatory biomarkers (GlycA/CRP), body composition (BMI / waist circumference) and cardiometabolic risk factors (blood pressure, triglycerides, HDL-c, glucose, insulin, and homeostasis model of insulin resistance [HOMA_IR]), were measured at baseline and again in 9-10 year follow-up. Metabolic ...
Background: 3D speckle-tracking echocardiography (3D-STE) is a novel method to quantify left vent... more Background: 3D speckle-tracking echocardiography (3D-STE) is a novel method to quantify left ventricular (LV) mechanical dyssynchrony. 3D-STE is influenced by image quality, but studies on the magnitude of its effect on 3D-STE derived LV systolic dyssynchrony indices (SDIs) and their test-retest reproducibility are limited. Methods: 3D-STE was performed in two groups, each comprising 18 healthy volunteers with good echocardiographic windows. In study 1, optimal and inferior-quality images, by intentionally poor echocardiographic technique, were acquired. In study 2, sub-optimal quality images were acquired by impairing ultrasound propagation using neoprene rubber sheets (thickness 2, 3, and 4 mm) mimicking mildly, moderately, and severely impaired images, respectively. Measures (normalized to cardiac cycle duration) were volume-and strain-based SDIs defined as the standard deviation of time to minimum segmental values, and volume-and strain-derived dispersion indices. For both studies test-retest reproducibility was assessed. Results: Test-retest reproducibility was better for most indices when restricting the analysis to good quality images; nevertheless, only volume-, circumferential strain-, and principal tangential strain-derived LV dyssynchrony indices achieved fair to good reliability. There was no evidence of systematic bias due to sub-optimal quality image. Volume-, circumferential strain-, and principal tangential strain-derived SDIs correlated closely. Radial strain-and longitudinal strain-SDI correlated moderately or weakly with volume-SDI, respectively. Conclusions: Sub-optimal image quality compromised the reliability of 3D-STE derived dyssynchrony indices but did not introduce systematic bias in healthy individuals. Even with optimal quality images, only 3D-STE indices based on volume, circumferential strain and principal tangential strain showed acceptable test-retest reliability.
BACKGROUND AND PURPOSE Hypoxia causes vasodilatation of coronary arteries, but the underlying mec... more BACKGROUND AND PURPOSE Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca 2+ concentration ([Ca 2+ ]i) by opening of K channels and release of H2S. EXPERIMENTAL APPROACH Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca 2+ ]i, and the expression of voltage-gated K channels KV7 channels (encoded by KCNQ genes) and large-conductance calcium-activated K channels (KCa1.1) was examined. Voltage clamp assessed the role of KV7 channels in hypoxia. KEY RESULTS Gradual reduction of oxygen concentration from 95 to 1% dilated the precontracted coronary arteries and this was associated with reduced [Ca 2+ ]i in PGF2α (10 μM)-contracted arteries whereas no fall in [Ca 2+ ]i was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and KCa1.1 inhibited hypoxia-induced dilatation in PGF2α-contracted arteries; this inhibition was more marked in the presence of the Kv7 channel blockers, XE991 and linopirdine, while a KV7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H2S-and adenosine-induced vasodilatation. PCR revealed the expression of KV7.1, KV7.4, KV7.5 and KCa1.1 channels, and KCa1.1, KV7.4 and KV7.5 were also identified by immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more marked in hypoxic conditions. CONCLUSION The KV7.4 and KV7.5 channels, which we identified in the coronary arteries, appear to have a major role in hypoxia-induced vasodilatation. The voltage clamp results further support the involvement of KV7 channels in this vasodilatation. Activation of these KV7 channels may be induced by H2S and adenosine.
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...
Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in ... more Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status. Methods: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. Results: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (−0.012 mm, 95% CI −0.
weight after 1 year, and 24.1 kg more after 2 years, than the 7,124 lifestyle modification patien... more weight after 1 year, and 24.1 kg more after 2 years, than the 7,124 lifestyle modification patients. On average, surgery led to a 3.2 (95% confidence interval 1.4 to 5.0) mmHg lower systolic blood pressure at year 1 and 3.5 (0.8 to 6.1) mmHg lower systolic blood pressure at year 2, in weighted analyses. Each 10 kg weight loss on average lead to a 2.1 (1.8 to 2.3) mmHg lower systolic blood pressure. Losing weight by surgery lead to a 1.1 (0.0 to 2.1) mmHg smaller blood pressure reduction than losing the same amount of weight by lifestyle treatment. Conclusion: Bariatric surgery lead to substantially greater weight loss and blood pressure reduction compared to intensive lifestyle modification, in this study of two large nationwide registries. The weight loss method per se had a small effect on blood pressure.
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 ...
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Papers by Alun Hughes