Gaston Kapuku

Cardiovascular Reactivity and Development of Preclinical and Clinical Disease States

Objective The objective of this review is to evaluate the evidence for the hypothesis that cardiovascular reactivity can predict the development of preclinical (elevated blood pressure, ventricular remodeling, carotid atherosclerosis) and/or clinical cardiovascular disease states. Methods A review of the literature was conducted examining prospective studies. Results Three large epidemiological studies with long-term follow-up periods (20 years or more) have found blood pressure responses to the cold pressor task to be predictive of subsequent essential hypertension in initially normotensive samples. Studies showing less consistent results have tended to use shorter-term follow-up periods. A larger body of literature demonstrates consistent associations between stress-related cardiovascular reactivity and blood pressure elevations in youth over the course of 1 to 6 years; such relationships have not been consistently shown among adult samples. Moderately consistent evidence points to a positive relationship between reactivity and other measures of subclinical disease (increased left ventricular mass and carotid atherosclerosis) among the few prospective studies that have examined these issues to date. A number of additional factors, however, such as baseline levels of disease risk and exposure to psychosocial stress, seem to moderate these relationships. Health status at baseline also seems to moderate the association between reactivity and clinical coronary heart disease in recent reports: two of three existing studies in initially healthy samples show no evidence of a relationship between reactivity and clinical outcomes, whereas three of four studies in samples with preexisting coronary heart disease or essential hypertension show a positive relationship between reactivity and subsequent disease states. Conclusions There is reasonable evidence to suggest that cardiovascular reactivity can predict the development of some preclinical states (eg, increased left ventricular mass and blood pressure) states and perhaps even new clinical events in some patients with essential hypertension or coronary heart disease. However, much more information is needed concerning moderating and potentially confounding variables before the robustness of the positive relationships can become clinically useful.

Hemodynamic Function at Rest, During Acute Stress, and in the Field Predictors of Cardiac Structure and Function 2 Years Later in Youth

Left ventricular hypertrophy is an independent predictor of cardiovascular morbidity and mortality. However, predictors of cardiac structure and function in youth are not completely understood. On 2 occasions (2.3 years apart), we examined 146 youth aged initially 10 to 19 years (mean age, 14.2+/-1.8 years). On the initial visit, hemodynamic function was assessed at rest, during laboratory stress (ie, orthostasis, car-driving simulation, video game, and forehead cold), and in the field (ie, ambulatory blood pressure). Quantitative M-mode echocardiograms were obtained on both visits. On both visits, black compared with white youth had higher resting laboratory systolic blood pressure (P<0.02), greater relative wall thickness (P<0.003), greater left ventricular mass indexed by either body surface area or height(2.7) (P<0.01 for both), and lower midwall fractional shortening ratio (P<0.05). Hierarchical stepwise regression analysis indicated that significant independent predictors of follow-up left ventricular mass/height(2. 7) were the initial evaluation of left ventricular mass/height(2.7), body mass index, gender (males more than females), and supine resting total peripheral resistance (final model R(2)=0.53). Left ventricular mass/body surface area was predicted by initial left ventricular mass/body surface area, weight, gender, mean supine resting total peripheral resistance, and systolic pressure response to car-driving simulation (final model R(2)=0.48). Midwall fractional shortening was predicted by initial midwall fractional shortening, race (white more than black), and lower mean supine total peripheral resistance (final model R(2)=0.13). The clinical significance of these findings and their implications for improved prevention of cardiovascular diseases are yet to be determined.

Racial Differences in Endothelin-1 at Rest and in Response to Acute Stress in Adolescent Males

Blacks exhibit greater vasoconstriction-mediated blood pressure (BP) increases in response to stress than do whites. Endothelin-1 (ET-1), a potent vasoconstrictive peptide, has been proposed as having a role in racial differences in stress reactivity. We evaluated the hemodynamic and plasma ET-1 levels of 41 (23 whites, 18 blacks, mean age 18.6 years) normotensive adolescent males at rest and in response to a video game challenge and forehead cold stimulation. Measurements were performed at catheter insertion and before and immediately after the 2 stressors, which were separated by 20-minute rest periods. Blacks exhibited higher absolute levels of diastolic blood pressure, total peripheral resistance index, or both in response to catheter insertion and to the video game challenge and during recovery from video game challenge and cold stimulation (P<0. 05 for all). Blacks exhibited higher absolute levels of ET-1 at every evaluation point (P<0.05 for all) and greater increases in ET-1 in response to both stressors (ps<0.05). These findings suggest that altered endothelial function may be involved in racial differences in hemodynamic reactivity to stress and possibly in the development of essential hypertension.

Growth of Left Ventricular Mass in African American and European American Youth

Increased left ventricular mass has been established as a strong risk factor for cardiovascular morbidity and mortality. To evaluate growth of left ventricular mass from childhood into early adulthood and its possible sociodemographic, anthropometric, and hemodynamic moderators, individual growth curves across age of left ventricular mass were created for 687 African American and European American males and females with a maximum of 10 annual assessments (age, 8.2 to 27.5 years). African Americans and males had significantly greater left ventricular mass (P <0.001) than did European Americans and females, respectively. Males also showed a larger rate of change in left ventricle mass than did girls (P <0.001). The ethnicity and gender effects on left ventricular mass only became apparent in early adolescence, and they persisted when controlling for socioeconomic status and anthropometric and hemodynamic variables. Body mass index and height were the strongest anthropometric predictors, and pulse pressure was the strongest hemodynamic predictor of left ventricular mass. Although significant, the contribution of pulse pressure to the prediction of left ventricular mass was small, once body mass index and height were entered into the model. The results of the present study suggest that increased left ventricular mass in boys and African Americans has its origin in late childhood. Apart from these ethnicity and gender effects, individual differences in cardiac growth can mainly be explained by body growth and increases in general adiposity.

Relationships among socioeconomic status, stress induced changes in cortisol, and blood pressure in african american males

The inverse relation between socioeconomic status (SES) and cardiovascular disease (CVD) risk has been posited to be partially due to exaggerated cardiovascular reactivity (CVR) to stress. Stress elicits hypothalamic-pituitary-adrenal axis activation (e.g., increased cortisol secretion), which may contribute to subsequent blood pressure (BP) elevation. Univariate associations among SES, cortisol secretion, and aggregated change scores to stressors (i.e., video game and forehead cold) for systolic BP (SBP) and diastolic BP (DBP) were assessed in a sample of 24 African American males (M age = 18.8, ± 2.7 years). Circadian variability of cortisol level was taken into account by partialling out collection time. Family SES was inversely related to initial cortisol level (partial r = -.46, p < .03). Neighborhood SES was inversely related to DBP reactivity (r = -.41, p < .05). The change in cortisol level during the stressor protocol was related to SBP reactivity (partial r = .44, p < .05). These results suggest that SES may be linked to CVD via BP and cortisol reactivity to stress, but prospective studies are needed to clarify whether such is the case.

Relationship of Visceral Adiposity to Cardiovascular Disease Risk Factors in Black and White Teens

Objective: We tested the hypothesis that visceral adiposity, compared with general adiposity, would explain more of the variance in cardiovascular disease (CVD) risk factors.

Cardiovascular (CV) responsivity and recovery to acute stress and future CV functioning in youth with family histories of CV disease: a 4-year longitudinal study

Blood pressure (BP) and heart rate (HR) data obtained during supine rest, in response to and recovery from four laboratory stressors in a baseline year were used to predict supine resting BP and HR values obtained during each of four consecutive annual follow-up evaluations. Subjects were 385 normotensive youth [95 African American (AA) males, 106 AA females, 92 European American (EA) males, 92 EA females] (mean age 12.7+/-2.6 at baseline year) with a positive family history of cardiovascular disease (CVD). During the baseline evaluation subjects were presented with four laboratory stressors (namely, postural change, video game challenge, social competence interview, and parent--child conflict discussion). The BP and HR values taken during each of the laboratory stressors and during the post stressor recovery periods were converted to z-scores which were averaged to yield aggregate measures for systolic and diastolic BP and HR responsivity and recovery. The data obtained during the baseline evaluation were subsequently used to predict the follow-up values of supine resting BP and HR. The prediction models were fairly consistent across each of the 4 follow-up years. Responsivity or recovery accounted for up to 6% of the total variance after accounting for baseline values. Within the prediction models responsivity or recovery accounted for 4--56% of the variance. The predictive value of the derived models did not decline from one annual evaluation to the next over the length of the study. CV recovery may supplement resting and responsivity in the prediction of future development of CVD

Insulin Resistance Syndrome and Left Ventricular Mass in Healthy Young People

Background: Findings of atherosclerotic plaques in adolescents, in the context of current epidemics of obesity and type 2 diabetes in youth, demand investigation into early cardiovascular risk development. Left ventricular hypertrophy has been linked to hypertension, obesity, and insulin resistance. Methods: Insulin resistance syndrome characteristics (fasting glucose and insulin; systolic blood pressure; waist girth) were measured in 70 normotensive, normoglycemic young people (60% male, 62% black; included 13 twin pairs; age mean±SD, 19±2.6 years). Left ventricular mass indexed by height2.7 (LVMI) was obtained via ultrasound. Twin pairs were clustered to satisfy the assumption for independent observations. Results: LVMI was regressed on insulin after controlling for race, gender, and systolic blood pressure. Insulin was a significant (P=0.02) independent predictor of LVMI (R2change=0.09, P<0.01). Waist girth accounted for an additional 4% variance of LVMI (P=0.05). A one‐factor model comprising waist (factor loading=0.83), insulin (0.59), glucose (0.42), and LVMI (0.46) showed good fit [χ2(2)=0.41, P=0.81; root‐mean‐square error of approximation=0.0]. Conclusions: A subclinical metabolic syndrome is detectable early in life, before abnormal fasting glucose or high blood pressure appear. Evidence of excessive load on the heart is associated with the metabolic syndrome even after accounting for the effects of race, gender, and blood pressure. Cardiac structure seems as closely associated with this syndrome as fasting glucose level. Based on this evidence, we propose that increased left ventricular mass is a part of insulin resistance syndrome and adds to the need for preventive public health measures to improve health behaviors and cardiovascular risk status in US youth.

Patterns of body fat deposition in youth and their relation to left ventricular markers of adverse cardiovascular prognosis

The patterns of body fat deposition in healthy youth and their relation to future development of cardiovascular disease remain incompletely understood. To further evaluate these patterns, we measured indirect indexes of central and general fat deposition in healthy adolescents (mean age 15.4+/-2.3 years) with family histories of hypertension. We examined the relation between these indexes and echocardiographic markers of adverse prognosis as well as the effect of gender and ethnicity. All 225 subjects (64% black and 48% female) had > or =1 biologic parent and 1 grandparent with hypertension. Skinfold thicknesses, waist-to-hip girth ratio, Quetelet index, Ponderal index, conicity, and Z score weight - Z score height were measured. Left ventricular (LV) mass, indexed LV mass, relative wall thickness (RWT), and midwall fractional shortening (MFS) were determined using echocardiography. In both black and white subjects, the adiposity indexes were significantly correlated with posterior wall thickness, total LV mass, and indexed LV mass (p <0.05 for all). Additionally, in black subjects, central adiposity was inversely related to MFS and directly related to RWT and septal thickness. General adiposity independently predicted indexed and nonindexed LV mass, whereas central adiposity predicted MFS and RWT. Compared with subjects with normal LV geometry, those with abnormal geometry were heavier and fatter based on every index of obesity (p <0.03 for all). Thus, indexes of fat deposition are significantly correlated with LV markers of adverse prognosis in healthy youth.

Adverse Childhood Experiences Are Associated With Detrimental Hemodynamics and Elevated Circulating Endothelin-1 in Adolescents and Young Adults

Growing evidence suggests that adverse childhood experiences (ACEs) increase the risks for coronary heart disease and hypertension in mid and late adulthood. We previously reported that early life stress induces a hyperreactive endothelin-dependent cardiovascular phenotype in a rat model. In the present study, we evaluated whether exposure to ACEs is associated with greater peripheral resistance, arterial stiffness, blood pressure, or elevated circulating endothelin-1 levels in humans. In 221 healthy adolescents and young adults (mean age, 21 years; range, 13–29 years), we found a graded association of ACE exposure with plasma endothelin-1 levels, of which on average 18% and 24% were higher in participants with 1 ACE and ≥2 ACEs, respectively, compared with those with no ACEs (P=0.001). Participants with moderate/severe exposure to ACEs (≥2 ACEs) had significantly higher total peripheral resistance index (+12%), diastolic blood pressure (+5%), and pulse wave velocity (+9%) compared with those who were not exposed. These associations were independent of age, race, sex, body mass index, and childhood socioeconomic status. Our results indicate that early life stress promotes cardiovascular disease risk, specifically detrimental vascular and cardiac function, detectable in young adulthood.