Alicja Rapala

Ethnic Differences in Carotid Intima-Media Thickness Between UK Children of Black African-Caribbean and White European Origin

Background and Purpose— UK black African-Caribbean adults have higher risks of stroke than white Europeans and have been shown to have increased carotid intima-media thickness (cIMT). We examined whether corresponding ethnic differences in cIMT were apparent in childhood and, if so, whether these could be explained by ethnic differences in cardiovascular risk markers. Methods— We conducted a 2-stage survey of 939 children (208 white European, 240 black African-Caribbean, 258 South Asian, 63 other Asian, 170 other ethnicity), who had a cardiovascular risk assessment and measurements of cIMT at mean ages of 9.8 and 10.8 years, respectively. Results— Black African-Caribbean children had a higher cIMT than white Europeans (mean difference, 0.014 mm; 95% CI, 0.008–0.021 mm; P<0.0001). cIMT levels in South Asian and other Asian children were however similar to those of white Europeans. Among all children, cIMT was positively associated with age, systolic and diastolic blood pressure and inversely with combined skinfold thickness and serum triglyceride. Mean triglyceride was lower among black African-Caribbeans than white Europeans; blood pressure and skinfold thickness did not differ appreciably. However, adjustment for these risk factors had little effect on the cIMT difference between black African-Caribbeans and white Europeans. Conclusions— UK black African-Caribbean children have higher cIMT levels in childhood; the difference is not explained by conventional cardiovascular risk markers. There may be important opportunities for early cardiovascular prevention, particularly in black African-Caribbean children.

Assessing the causal role of body mass index on cardiovascular health in young adults: Mendelian randomization and recall-by-genotype analyses

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 on detailed measures of cardiovascular health in a population of young healthy adults. Methods and Findings Data from the Avon Longitudinal Study of Parents and Children were used. For MR analyses, a genetic risk score (GRS) comprising 97 independent single nucleotide polymorphisms (SNPs) and constructed using external weighting was used as an instrument to test the causal effect of each unit increase in BMI (kg/m2) on selected cardiovascular phenotypes measured at age 17 (N=7909). An independent enriched sample from the same cohort participated in a RbG study at age 21, which enabled more detailed cardiovascular phenotyping (N=418; 191/227 from the lower/upper ∼30% of a genome-wide GRS distribution predicting variation in BMI). The causal effect of BMI on the additional cardiovascular phenotypes was assessed by comparing the two recalled groups. Difference in mean BMI between RbG groups was 3.85kg/m2 (95% CI: 2.53, 4.63; P=6.09×1011). In both MR and RbG analyses, results indicated that higher BMI causes higher blood pressure (BP) and left ventricular mass (indexed to height2.7, LVMI) in young adults (e.g. difference in LVMI per kg/m2 using MR: 1.07g/m2.7; 95% CI: 0.62, 1.52; P=3.87×10−06 and per 3.58kg/m2 using RbG: 1.65g/m2.7 95% CI: 0.83, 2.47; P=0.0001). Additionally, RbG results indicated a causal role of higher BMI on higher stroke volume (SV; difference per 3.58kg/m2: 1.49ml/m2.04; 95% CI: 0.62, 2.35; P=0.001) and cardiac output (CO; difference per 3.58kg/m2: 0.11l /min/m1.83; 95% CI: 0.03, 0.19; P=0.01). Neither analysis supported a causal role of higher BMI on heart rate. Conclusions Complementary MR and RbG causal methodologies, together with a range of appropriate sensitivity analyses, showed that higher BMI is likely to cause worse cardiovascular health, specifically higher BP and LVMI, even in youth. These consistent results support efforts to prevent or reverse obesity in the young.

Know Your Heart: Rationale, design and conduct of a cross-sectional study of cardiovascular structure, function and risk factors in 4500 men and women aged 35-69 years from two Russian cities, 2015-18

Russia has one of the highest rates of cardiovascular disease in the world. The International Project on Cardiovascular Disease in Russia (IPCDR) was set up to understand the reasons for this. A substantial component of this study was the Know Your Heart Study devoted to characterising the nature and causes of cardiovascular disease in Russia by conducting large cross-sectional surveys in two Russian cities Novosibirsk and Arkhangelsk. The study population was 4542 men and women aged 35-69 years recruited from the general population. Fieldwork took place between 2015-18. There were two study components: 1) a baseline interview to collect information on socio-demographic characteristics and cardiovascular risk factors, usually conducted at home, and 2) a comprehensive health check at a primary care clinic which included detailed examination of the cardiovascular system. In this paper we describe in detail the rationale for, design and conduct of these studies.

Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease

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 (MT) from intimal thickness (IT) in CKD patients, identify their determinants and monitor their progression. Methods Fifty-four children and adolescents with CKD and 12 healthy controls underwent UHFUS measurements using 55-70MHz transducers in common carotid and dorsal pedal arteries. Annual follow-up imaging was performed in 31 patients. Results CKD patients had higher carotid MT and dorsal pedal IT and MT compared to controls. The carotid MT in CKD correlated with serum phosphate (p<0.001, r = 0.42), PTH (p = 0.03, r = 0.36) and mean arterial pressure (p = 0.03, r = 0.34). Following multivariable analysis, being on dialysis, serum phosphate levels and mean arterial pressure remained the only independent predictors of carotid MT (R2 64%). Transplanted children had lower carotid and dorsal pedal MT compared to CKD and dialysis patients (p = 0.02 and p = 0.01 respectively). At 1-year follow-up, transplanted children had a decrease in carotid MT (p = 0.01), but an increase in dorsal pedal IT (p = 0.04) that independently correlated with annualized change in BMI. Conclusions Using UHFUS, we have shown that CKD is associated with exclusively medial arterial changes that attenuate when the uremic milieu is ameliorated after transplantation. In contrast, after transplantation intimal disease develops as hypertension and obesity become prevalent, representing rapid vascular remodeling in response to a changing cardiovascular risk factor profile.

Submaximal exercise blood pressure and cardiovascular structure in adolescence

Purpose Dynamic exercise results in increased systolic blood pressure (BP). Irrespective of resting BP, some individuals may experience exaggerated rise in systolic BP with exercise, which in adulthood is associated with risk of hypertension, and cardiovascular (CV) disease. It is unknown if exercise BP is associated with markers of CV structure during adolescence. We examined this question in a large adolescent cohort taking account of the possible confounding effect of body composition and BP status. Methods 4036 adolescents (mean age 17.8 ± 0.4 years, 45% male), part of a UK population-based birth cohort study completed a sub-maximal step-test with BP immediately post-exercise. Sub-samples underwent comprehensive echocardiography for assessment of cardiac structure; arterial structure including aortic pulse wave velocity (PWV) and carotid intima-media thickness; and assessment of body composition by dual-energy X-ray absorptiometry (DXA). Results Each 5 mm Hg higher post-exercise systolic BP was associated with CV structure, including 0.38 g/m2.7 (95% CI: 0.29, 0.47) greater left-ventricular mass index (LVMI), and 0.04 m/s (95% CI: 0.03, 0.04) greater aortic PWV. Adjustment for age, total body fat, lean mass and BP status attenuated, but did not abolish associations with LVMI (0.14 g/m2.7 per 5 mm Hg of post-exercise systolic BP; 95% CI 0.21, 0.39) or aortic PWV (0.03 m/s per 5 mm Hg of post-exercise systolic BP; 95% CI: 0.02, 0.04). Conclusion Submaximal exercise systolic BP is associated with markers of CV structure in adolescents. Given the clinical relevance of exercise BP in adulthood, such associations may have implications for CV disease screening in young people and risk in later life.

DETERMINANTS OF DEVELOPMENT OF STRUCTURAL ARTERIAL DISEASE IN YOUNG ADULTHOOD: THE ALSPAC STUDY

background: Endothelial dysfunction is an early event in the development of cardiovascular disease and has been associated with adverse cardiovascular outcome in adulthood. In the largest longitudinal study of Parents and Children (ALSPAC) we investigated whether endothelial function and change in cardiovascular risk factors from childhood to adulthood can explain the development of structural arterial disease in young adulthood.

INCREASED SMOKING AND ALCOHOL EXPOSURE IN ADOLESCENCE HAS AN ADVERSE EFFECT ON ARTERIAL STIFFNESS IN YOUNG ADULTHOOD: THE ALSPAC STUDY

Increased alcohol consumption and cigarette smoking have been associated with an adverse cardiovascular profile in adults. However their influence on the development of early arterial disease remains unknown. We set out to investigate the influence of alcohol and smoking exposure in adolescence on

HIGHER ADIPOSITY EXPOSURE SINCE CHILDHOOD IS ASSOCIATED WITH INCREASED ARTERIAL STIFFNESS IN YOUNG FEMALES: THE ALSPAC STUDY

Increased adiposity has been associated with worse cardiovascular (CV) outcome. We examined whether exposure to adiposity in childhood and adolescence has a cumulative adverse effect on CV risk factor profile and arterial stiffness in young adulthood. The study population consisted of 4364 subjects

THE ASSOCIATION OF WAIST CIRCUMFERENCE AND PHYSICAL ACTIVITY IN ADOLESCENCE ON ARTERIAL STIFFNESS IN YOUNG ADULTHOOD

Greater physical activity (PA) has been consistently shown to improve cardiovascular (CV) health and a number of studies suggested that it can modify the adverse effect of adiposity on arterial disease in adults. However its role in adolescence remains largely unexplored. In the largest longitudinal