Karen L. Miles

Use of the oral contraceptive pill is associated with increased large artery stiffness in young women: the ENIGMA study.

Background The oral contraceptive pill (OCP) is widely prescribed throughout the world. Although it is associated with a small but significant increase in blood pressure, the influence of the OCP on large artery stiffness and wave reflection is unclear. The aim of this study was to determine the relationship between use of the OCP and aortic stiffness and wave reflections in a young, healthy cohort of women. Methods Participants were drawn from the ENIGMA study, which examines the natural history of blood pressure in young adults. A detailed medical history and lifestyle questionnaire, including OCP details were taken. Blood pressure was measured according to the British Hypertension Society guidelines. Aortic pulse wave velocity (aPWV) was measured together with augmentation index (AIx). Stroke volume (SV) and cardiac output (CO) were also assessed. Results Women taking the OCP (n = 225) had a higher SBP and pulse pressure compared with nonusers (n = 660; 112 ± 12 vs. 110 ± 11 and 43 ± 8 vs. 42 ± 8 mmHg, respectively, P < 0.05 for both). CO and SV were also higher (6.6 ± 1.5 vs. 6.3 ± 1.5 l/min, P < 0.01 and 81 ± 16 vs. 78 ± 19 ml, P < 0.05) as was aPWV (5.5 ± 0.7 vs. 5.4 ± 0.7 m/s, P < 0.05). However, there was no difference in DBP (68 ± 9 vs. 69 ± 9 mmHg), mean arterial pressure (81 ± 10 vs. 81 ± 10 mmHg) or AIx (2 ± 12 vs. 3 ± 13%) between the groups. Conclusion Use of the OCP is associated with elevated pulse pressure and SV and a small increase in aPWV in young women. The longer term implications of these effects require further investigation.

The impact of birth weight on blood pressure and arterial stiffness in later life: the Enigma Study.

Background Accumulating evidence suggests that low birth weight is associated with increased cardiovascular risk. However, the relationship between birth weight, blood pressure, arterial stiffness and wave reflections as putative mechanisms is controversial. Method Data from 882 participants (mean age 21 years) were analysed. Participants underwent a detailed physiological assessment, including anthropometric measurement, blood pressure, aortic pulse wave velocity, augmentation index (AIx) and cardiac output (CO). Analyses were conducted in men and women separately, according to birth weight quartiles and categories referenced to UK birth weight percentiles. Results In men, those in the lowest birth weight quartile had higher brachial SBP (P = 0.04), central pulse pressure (PP; P = 0.03) and AIx (P = 0.02). Further analysis of the low birth weight spectrum revealed that central PP (P = 0.03), AIx (P = 0.03) and peripheral vascular resistance index (P = 0.01) were higher in those in the lowest birth weight percentile, although the association with AIx disappeared after adjustment for adult height. In women, analysis by birth weight quartiles and categories referenced to UK birth weight percentiles revealed a significant positive association between birth weight and CO (P = 0.04, P = 0.02) and stroke volume (P = 0.03, P = 0.002); although these associations disappeared when body size was taken into account. There was no association between birth weight and aortic pulse wave velocity in either men or women. Conclusion These data suggest that although lower birth weight is associated with altered haemodynamics in young adulthood, the associations are predominantly driven by other factors such as adult body size, rather than intrinsic structural changes within the large elastic arteries.

Mechanisms underlying elevated SBP differ with adiposity in young adults: the Enigma study

Objectives: The positive association between adiposity and hypertension is well recognized. However, not all overweight individuals have elevated blood pressure (BP). Moreover, different factors may be associated with high BP in normal-weight versus overweight individuals. The aim of the current study was to examine the influence of adiposity on the relationship between SBP and underlying haemodynamic mechanisms in young adults. Method: Data from 2502 patients were available from the Enigma study. Detailed demographic, biochemical, and haemodynamic data were obtained in all individuals. Data were analysed between lower and upper tertiles of BMI and SBP, separately for each sex. Results: In normal-weight individuals, cardiac output (CO) was elevated in those with higher SBP, independently of body size. Moreover, higher CO was associated with an increased stroke volume in men (P < 0.001), but an increased heart rate in women (P = 0.002). In contrast, in overweight individuals, peripheral vascular resistance (PVR) was elevated in men with higher SBP (P = 0.02) and those with lower SBP had the lowest PVR of all groups. In linear regression analyses, there was a stronger association between SBP and CO in normal-weight individuals, but a stronger association between SBP and PVR in overweight individuals. Conclusion: Different haemodynamic mechanisms are associated with elevated SBP in young adults, depending on body size and sex. These data suggest the need for differential approaches to the identification and management of young adults with elevated BP.

Surrogate markers of cardiovascular risk and chronic obstructive pulmonary disease

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid–femoral (aortic) pulse wave velocity, augmentation index, and carotid intima–media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima–media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease.

Mechanisms underlying elevated systolic blood pressure differ with adiposity in young adults: The Enigma Study

Objectives: The positive association between adiposity and hypertension is well recognized. However, not all overweight individuals have elevated blood pressure (BP). Moreover, different factors may be associated with high BP in normal-weight versus overweight individuals. The aim of the current study was to examine the influence of adiposity on the relationship between SBP and underlying haemodynamic mechanisms in young adults. Method: Data from 2502 patients were available from the Enigma study. Detailed demographic, biochemical, and haemodynamic data were obtained in all individuals. Data were analysed between lower and upper tertiles of BMI and SBP, separately for each sex. Results: In normal-weight individuals, cardiac output (CO) was elevated in those with higher SBP, independently of body size. Moreover, higher CO was associated with an increased stroke volume in men (P < 0.001), but an increased heart rate in women (P = 0.002). In contrast, in overweight individuals, peripheral vascular resistance (PVR) was elevated in men with higher SBP (P = 0.02) and those with lower SBP had the lowest PVR of all groups. In linear regression analyses, there was a stronger association between SBP and CO in normal-weight individuals, but a stronger association between SBP and PVR in overweight individuals. Conclusion: Different haemodynamic mechanisms are associated with elevated SBP in young adults, depending on body size and sex. These data suggest the need for differential approaches to the identification and management of young adults with elevated BP.

Mechanisms underlying elevated SBP differ with adiposity in young adults

Objectives: The positive association between adiposity and hypertension is well recognized. However, not all overweight individuals have elevated blood pressure (BP). Moreover, different factors may be associated with high BP in normal-weight versus overweight individuals. The aim of the current study was to examine the influence of adiposity on the relationship between SBP and underlying haemodynamic mechanisms in young adults. Method: Data from 2502 patients were available from the Enigma study. Detailed demographic, biochemical, and haemodynamic data were obtained in all individuals. Data were analysed between lower and upper tertiles of BMI and SBP, separately for each sex. Results: In normal-weight individuals, cardiac output (CO) was elevated in those with higher SBP, independently of body size. Moreover, higher CO was associated with an increased stroke volume in men (P < 0.001), but an increased heart rate in women (P = 0.002). In contrast, in overweight individuals, peripheral vascular resistance (PVR) was elevated in men with higher SBP (P = 0.02) and those with lower SBP had the lowest PVR of all groups. In linear regression analyses, there was a stronger association between SBP and CO in normal-weight individuals, but a stronger association between SBP and PVR in overweight individuals. Conclusion: Different haemodynamic mechanisms are associated with elevated SBP in young adults, depending on body size and sex. These data suggest the need for differential approaches to the identification and management of young adults with elevated BP.

NORMAL BLOOD PRESSURE IN OBESITY IS ASSOCIATED WITH REDUCED PERIPHERAL VASCULAR RESISTANCE: 8B.05

Objective: The link between obesity and elevated blood pressure is firmly established. However, not all obese individuals are hypertensive, suggesting that adaptive mechanisms are present in at least some obese individuals which allow them to maintain normal levels of blood pressure (BP). The aim of the current study was to examine the mechanisms underlying different levels of BP in obese individuals. Design and Method: Data from 2511 individuals (1262 males) were available from The Enigma Study for the current analyses. All individuals were aged between 18–40 years, and were free of cardiovascular disease and medication. Detailed demographic, biochemical and haemodynamic data, including BP, cardiac output (CO) and peripheral resistance (PVR) were obtained in all individuals. They were then stratified according to BMI (normal weight, overweight and obese) using WHO criteria, and seated brachial BP (optimal, normal, high-normal and hypertensive) using JNC 6 criteria. For the current analyses, comparisons were made between 3 groups: normal-weight normotensives (controls, optimal and normal BP, n = 1360), obese normotensives (optimal and normal BP, n = 61) and obese hypertensives (n = 79). Results: Compared with controls, obese individuals were older, had an increased family history of hypertension and an adverse biochemical profile (P < 0.01 for all). In addition, heart rate, CO and stroke volume were all significantly elevated in obese individuals (P < 0.001 for all). However, the elevation in CO was more marked in obese individuals who were hypertensive (P < 0.05 versus obese normotensives). In contrast, PVR was significantly lower in obese individuals with normal BP (P < 0.05 versus controls and obese hypertensives). Conclusions: These data suggest that a reduction in peripheral resistance is an important mechanism by which some obese individuals maintain normal blood pressure despite having a significantly elevated cardiac output. Although the factors underlying the reduction in PVR in these individuals remain to be elucidated, they are likely to provide an intriguing insight into the pathophysiology of obesity-related hypertension.

HYPERTENSION IN NORMAL-WEIGHT VERSUS OBESE INDIVIDUALS IS ASSOCIATED WITH DIFFERENT HAEMODYNAMIC MECHANISMS: PP.8.311

Objective: The aetiology of essential hypertension is complex, giving rise to a number of forms. Although recent attention has focussed on obesity and hypertension, different factors may be responsible for hypertension in non-obese individuals. Therefore, the aim of this study was to examine the factors underlying hypertension in normal weight versus obese individuals. Design and Method: Data from 2511 individuals (1262 males) were available from The Enigma Study. All individuals were aged between 18–40 years, and free of cardiovascular disease and medication. Detailed demographic, biochemical and haemodynamic data, including BP, cardiac output (CO) and peripheral resistance (PVR) were obtained in all. They were then stratified according to BMI (normal weight, overweight and obese) using WHO criteria, and seated brachial BP (optimal, normal, high-normal and hypertensive) using JNC 6 criteria. Comparisons were then made between 3 groups: normal-weight normotensives (controls, optimal and normal BP, n = 1360), normal weight hypertensives (n = 175) and obese hypertensives (n = 79). Results: Hypertensives were older, had a higher BMI, a greater family history of hypertension and an adverse biochemical profile compared with controls (P < 0.001 for all). In addition, heart rate and CO were significantly elevated in hypertensive individuals, but these differences were significantly greater in obese hypertensives (P < 0.05 versus normal-weight hypertensives and controls for both). Interestingly, when cardiac output was indexed to body size, there was no longer any difference between obese hypertensives and normotensive controls. In contrast, normal-weight hypertensives were characterised by a marked elevation of PVR, compared with obese hypertensives and controls (P < 0.05 for both). Conclusions: Different haemodynamic mechanisms are associated with hypertension in obese versus normal-weight individuals. The primary haemodynamic abnormality associated with obesity-related hypertension is a raised cardiac output, reflecting an increased perfusion in these individuals driven by their larger body size. In contrast, the primary disturbance in normal-weight hypertensives is an elevated PVR. These findings emphasise the need for differential approaches to the understanding, prevention and treatment of hypertension in young individuals.