Scott Chiesa

University College London | UCL · Institute of Cardiovascular Science

Aims: Excessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid- to late-life would be associated with subsequent...

Background Aortic stiffness is closely linked with cardiovascular diseases (CVDs), but recent studies suggest that it is also a risk factor for cognitive decline and dementia. However, the brain changes underlying this risk are unclear. We examined whether aortic stiffening during a 4-year follow-up in mid-to-late life was associated with brain str...

Background Excess bodyweight (BMI >25 kg/m²) in midlife (age 40-65 years) has been linked to future cognitive decline and an increased risk of dementia. Whether chronic exposure to excess bodyweight in the early decades of life (<40 years) is associated with compromised cognitive function by midlife, however, remains unclear. This study therefore a...

Obese adults are often reported to have smaller brain volumes than their non-obese peers. Whether this represents evidence of accelerations in obesity-driven atrophy or is instead a legacy of developmental differences established earlier in the lifespan remains unclear. This study aimed to investigate whether early-life differences in adiposity e...

Background Cumulative exposures to obesity, hypertension, and physical inactivity from midlife (40-65 years) onwards are three known cardiovascular risk factors for dementia and associated cerebral structural damage. Exactly how early in the lifespan sensitive periods for exposure to these risk factors begin is yet to be established, specifically w...

Near-infrared spectroscopy (NIRS) is an optical technique that can be used to non-invasively interrogate haemodynamic changes within skeletal muscle. It can be combined with a short (3-5 minute) arterial cuff-occlusion to quantify post-occlusive reactive hyperaemia (PORH). This technique has utility in tracking changes in vascular health in relatio...

Background Lifestyle risk factors for coronary artery disease (CAD) have been associated with neurodegeneration and dementia. Whether an underlying genetic risk for the development of CAD further increases this risk, however, remains unclear. Purpose To examine whether an increased genetic risk for CAD is associated with an increased risk of demen...

Introduction Obesity in young adulthood is associated with various cardiovascular structural and functional changes, commonly used as markers of early subclinical cardiovascular disease. Whether these changes occur predominantly in relation to increased fat mass (FM) or are instead more closely related to simultaneous increases in underlying fat-fr...

Background: Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) and dementia. This study aimed to examine if an increased genetic risk for CAD is associated with long-term risk of developing all-cause, Alzheimer's, or vascular dementia, and investigate whether the presence of healthy lifestyl...

Introduction & Background Epochs of hyperglycaemia and hypoglycaemia may each increase risk of common chronic diseases and impair both cognitive and physical function even in people without diabetes. Older people may have greater frequency of adverse glycaemic excursions, partly due to disordered autonomic function and sleep quality. Data for older...

Background Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. Methods Retrospective, cr...

Introduction: Childhood-onset type 1 diabetes (T1D) is associated with an increased risk of premature cardiovascular mortality. Objectives: This study aimed to assess the evolution of subclinical vascular damage in young people with T1D as they transitioned through adolescence. Methods: Repeated vascular phenotyping was performed in early adolescen...

Identifying genetic determinants for longitudinal changes in albumin excretion in individuals with type 1 diabetes may help identify those that are predisposed to renal, retinal and cardiovascular complications. Most studies have focussed on genetic predisposition to diabetic kidney disease and used cross-sectional measurements of urinary albumin e...

The factors influencing survival during severe infection are unclear. Extracellular chromatin drives pathology, but the mechanisms enabling its accumulation remain elusive. Here, we showed that in murine sepsis models, splenocyte death interfered with chromatin clearance through the release of the DNase I inhibitor actin. Actin inhibition was compe...

Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic,...

Inflammation plays a crucial role in the onset and development of atherosclerosis. Periodontitis is a common chronic disease linked to other chronic inflammatory diseases such as atherosclerotic cardiovascular disease (ASCVD). The mechanistic pathways underlying this association are yet to be fully understood. This critical review aims at discuss t...

Background and aims Perinatal HIV infection (PHIV) and prolonged use of antiretroviral therapy (ART) may increase the likelihood of developing subclinical vascular dysfunction at an early age. We conducted a systematic review to assess the effect of PHIV and ART on intima-media thickness (IMT), arterial stiffness and endothelial function in individ...

Aims/hypothesis We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control. Methods This was a prospective observational study in 710 normoalbuminuric...

Background Low‐grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high‐sensitivity CRP (C‐re...

Hyperinflammation, coagulopathy and immune dysfunction are prominent in patients with severe infections. Extracellular chromatin clearance by plasma DNases suppresses such pathologies in mice but whether severe infection interferes with these pathways is unclear. Here, we show that patients with severe SARS-CoV-2 infection or microbial sepsis exhib...

Objective Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemia-reperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammat...

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in individuals with type 1 diabetes (T1D). Adolescence appears to be a critical time for the development of early subclinical manifestations of CVD, with these changes likely driven by a transient deterioration in glycemic control during the progression through puberty,...

Background It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart–brain associat...

Objective: in children aged 8-9 years, we examined the associations of linear and abdominal circumference (AC) growth during critical stages of pre- and post-natal development with six vascular measurements commonly used as early markers of atherosclerosis and later CVD risk. 64 Methods: in 724 children from the UK Southampton Women’s Survey mothe...

Objectives: This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years. Background: Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. Methods:...

Background Aortic stiffness, assessed by carotid‐femoral pulse wave velocity (PWV), is closely linked with hypertension, heart disease and stroke. Recent research has suggested that rapid aortic stiffening may also be a risk factor for cognitive decline and dementia. However, the age of onset of this risk and its underlying brain physiology is unkn...

An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period a...

Objective: Low-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 inve...

Objectives To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. Methods Twenty‐five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median[interquartile range] age: 13.9[12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardiorenal...

Background: Aortic stiffness is closely linked with cardiovascular diseases, but recent studies suggest that it is also a risk factor for cognitive decline and dementia. However, the brain changes underlying this risk are unclear. We examined whether aortic stiffening in the transition from mid to late-life affects brain structure and cognition. Me...

Increased carotid intima-media thickness (cIMT) is reported in both adults and children with human immunodeficiency virus (HIV) in high income settings and is associated with an increased risk of cardiovascular disease, but data from sub-Saharan Africa is lacking. We assessed cIMT using ultrasound in perinatally HIV-infected children aged 6 to 16 y...

OBJECTIVE Suboptimal adherence to insulin treatment is a main issue in adolescents with type 1 diabetes. However, to date, there are no available data on adherence to adjunct noninsulin medications in this population. Our aim was to assess adherence to ACE inhibitors and statins and explore potential determinants in adolescents with type 1 diabetes...

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This commentary refers to ‘Early vascular damage from smoking and alcohol in teenage years: the ALSPAC study’, by M. Charakida et al., 345–353.

Genetic, experimental and clinical studies have consistently confirmed that inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) can result in significant LDL-C lowering and two fully human PCSK9 mononclonal antibodies have received regulatory approval for use in high-risk patients. Co- administration of PCSK9 with statins has result...

Background: The link between adiposity, metabolic abnormalities, and arterial disease progression in children and adolescents remains poorly defined. We aimed to assess whether persistent high adiposity levels are associated with increased arterial stiffness in adolescence and any mediation effects by common metabolic risk factors. Methods: We i...

Background: This case-report characterized the respiratory, cardiovascular, and nutritional/gastrointestinal (GI) responses of a trained individual to a novel ultra-endurance exercise challenge. Case Presentation: A male athlete (age 45 years; V ˙ O2max 54.0 mL⋅kg-1⋅min-1) summited 100 mountains on foot in 25 consecutive days (all elevations >60...

High-density lipoprotein cholesterol (HDL-c) has long been referred to as ‘good cholesterol’ due to its apparent inverse relationship with future CVD risk. More recent research has questioned a causal role for HDL-c in this relationship, however, as both genetic studies and numerous large-scale randomised controlled trials have found no evidence of...

Aims: High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not be...

Progressive whole-body hyperthermia with passive heat stress is associated with a host of physiological adjustments. These include large increases in peripheral blood flow and cardiac output and a smaller selective redistribution of blood flow from the cerebral and visceral tissues to the limbs, head, and torso, with perfusion pressure being only s...

Progressive whole-body hyperthermia with passive heat stress is associated with a host of physiological adjustments. These include large increases in peripheral blood flow and cardiac output and a smaller selective redistribution of blood flow from the cerebral and visceral tissues to the limbs, head, and torso, with perfusion pressure being only s...

Rising rates of adiposity in the young pose one of the greatest threats to future population burden of cardiovascular disease. Understanding the contribution of genetic and early-life influences to adiposity profiles in young adulthood - when the first signs of subclinical cardiovascular disease commonly appear - are vital if effective lifetime pre...

Objective—Childhood body mass index (BMI) has been related to vascular structure and function. However, little is known about the differing contributions of fat and lean mass to this relationship. Our objectives were to relate the fat and lean mass (bone excluded) components of BMI (fat mass index and lean mass index; mass [kg]/height [m]2) to vasc...

Aims: To determine the impact of smoking and alcohol exposure during adolescence on arterial stiffness at 17 years. Methods and results: Smoking and alcohol use were assessed by questionnaires at 13, 15, and 17 years in 1266 participants (425 males and 841 females) from the ALSPAC study. Smoking status (smokers and non-smoker) and intensity (‘high’...

BACKGROUND: Body mass index (BMI) has been suggested to be causally related to cardiovascular health in mid-to-late life, but this has not been explored systematically at younger ages—nor with detailed cardiovascular phenotyping. Recall-by-Genotype (RbG) is an approach that enables the collection of precise phenotypic measures in smaller studies, w...

Objective: Baseline data from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) indicated that tertiles of urinary albumin-to-creatinine ratios (ACRs) in the normal range at age 10-16 years are associated with risk markers for diabetic nephropathy (DN) and cardiovascular disease (CVD). We aimed to determine whether the top ACR...

Background Patients with chronic kidney disease (CKD) are exposed to both traditional ‘Framingham’ and uremia related cardiovascular risk factors that drive atherosclerotic and arteriosclerotic disease, but these cannot be differentiated using conventional ultrasound. We used ultra-high-frequency ultrasound (UHFUS) to differentiate medial thickness...

Clinical and biochemical characteristics of the study population at baseline. (PDF)

Intense, large muscle mass exercise increases circulating microvesicles, but our understanding of microvesicle dynamics and mechanisms inducing their release remains limited. However, increased vascular shear stress is generally thought to be involved. Here, we manipulated exercise‐independent and exercise‐dependent shear stress using systemic heat...

Background Among adolescents with type 1 diabetes, rapid increases in albumin excretion during puberty precede the development of microalbuminuria and macroalbuminuria, long-term risk factors for renal and cardiovascular disease. We hypothesized that adolescents with high levels of albumin excretion might benefit from angiotensin-converting–enzyme...

Peripheral arterial disease (PAD) is a common atherosclerotic condition affecting the lower extremities. PAD patients share similar cardiovascular risk factors to coronary artery disease patients and suffer from increased cardiovascular morbidity and mortality. Statins have been widely used in coronary artery disease patients but have been underuse...

Background Mendelian randomization (MR) studies of body mass index (BMI) and cardiovascular health in mid-to-late life suggest causal relationships, but the nature of these has not been explored systematically at younger ages. Using complementary MR and recall-by-genotype (RbG) methodologies, our objective was to estimate the causal effect of BMI o...

Objective: To evaluate the association between a clustering of cardio-metabolic risk factors in parents and the development of microalbuminuria (MA) in their offspring with childhood-onset type 1 diabetes (T1D). Methods: The study population comprised 53 parents (mean age (±SD): 56.7±6.2 years) of 35 T1D young people with MA (MA+) and 86 parents (a...

Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat-stressed humans, however, the contribution of elevations in skin (T sk) versus whole body temperatures on exercise capacity has not been characterized. To ascertain their relationships with exercise capacity, blood temperature (T B), oxygen...

Purpose of review: Continuous wave near infrared spectroscopy (CW NIRS) provides non-invasive technology to measure relative changes in oxy- and deoxy-haemoglobin in a dynamic environment. This allows determination of local skeletal muscle O2 saturation, muscle oxygen consumption ([Formula: see text]) and blood flow. This article provides a brief...

New Findings What is the central question of this study? Skin and muscle blood flow increases with heating and decreases with cooling, but the temperature‐sensitive mechanisms underlying these responses are not fully elucidated. What is the main finding and its importance? We found that local tissue hyperaemia was related to elevations in ATP relea...

Purpose: Increased alcohol consumption and cigarette smoking have been associated with adverse cardiovascular outcomes in adulthood. These habits are often initiated in adolescence, however their role in the development of arterial disease remains unknown. In this study, we investigated the association between smoking and alcohol exposure on arteri...

Background: Increased inflammation and dyslipidemia are commonly reported in patients with type 1 diabetes (T1D) and further enhance cardiovascular risk. Moderate- to well-maintained glycaemic control in T1D is associated with a favourable lipid profile due to increased levels of HDL, but is not associated with a reduction in coronary heart disease...

Purpose: As treatment for cardiovascular disease improves and early prevention emerges as an important factor already in early adulthood, new, sensitive methods to evaluate progress of disease and treatment response are needed. Carotid IMT is used as a marker of arterial disease but cannot distinguish the nature of such disease. We used very high r...

Cardiovascular disease (CVD) is one of the leading global causes of morbidity and mortality. Although certain risk factors associated with CVD progression-such as age, gender, and family history-are nonmodifiable, the majority of factors influencing CVD risk can be attributed to an individual's lifestyle choices and, as such, have the potential to...