High sodium intake is associated with short leukocyte telomere length in overweight and obese adolescents.

BACKGROUND/OBJECTIVES: Telomere shortening has an important role in cellular aging. However, the impact of high sodium intake, an important risk factor of age-related diseases, on telomere shortening remains unknown. Therefore, we examined the relationship between high dietary sodium intake and leukocyte telomere length (LTL), particularly in the context of obesity, as obesity increases salt sensitivity. SUBJECTS/METHODS: LTL was determined by a quantitative polymerase chain reaction method in 766 adolescents aged 14-18 years (50% females, 49% African Americans). Dietary sodium intake was assessed by seven independent 24-h dietary recalls. We divided the sample into low sodium (mean 2388±522 mg per day) or high sodium groups (mean 4142±882 mg per day) based on the median value (3280.9 mg per day). RESULTS: In the entire cohort, there was no significant association between sodium intake and LTL (r=-0.05, P=0.24). However, there was a significant interaction between sodium intake and obesity status (P=0.049). Further multiple linear regression analyses revealed that higher dietary sodium intake was associated with shorter LTL in the overweight/obese group (body mass index ⩾85th percentile, ß=-0.37, P=0.04), but not in the normal-weight group (ß=0.01, P=0.93) after adjusting for multiple confounding factors. In the overweight/obese group, LTL was significantly shorter in the high sodium intake subjects vs low sodium intake subjects (1.24±0.22 vs. 1.32±0.20, P=0.02), but not the normal-weight group (1.29±0.24 vs 1.30±0.24, P=0.69). CONCLUSIONS: Higher dietary sodium intake is associated with shorter telomere length in overweight and obese adolescents.

Gender differences in diastolic function among youth.

BACKGROUND: Youth were studied to determine the influence of gender on diastolic function, which has been shown to express abnormalities early in the course of congestive heart failure. METHODS: The study participants were 121 normotensive individuals (53 girls, 68 boys) ages 14 to 18 years. Demographics, hemodynamics, and Doppler-derived indices of diastolic function were collected. Dependent measures of diastolic function were the ratio of early (E) to late (A) peak filling velocities and the isovolumetric relaxation time (IVRT). RESULTS: The girls had a higher relative wall thickness (RWT) (36.58% +/- 4.59% vs 34.60% +/- 4.01%; p < 0.02), higher A (48.40 +/- 8.47 cm/s vs 42.36 +/- 10.43 cm/s; p < 0.001), a lower E/A ratio (1.96 +/- 0.40 vs 2.38 +/- 0.68; p < 0.01), and a shorter IVRT (51.80 +/- 11.14 ms vs 59.00 +/- 14.36 ms; p < 0.01) than the boys. The differences in deceleration time were not significant (181.30 +/- 81.33 ms vs 170.30 +/- 31.06 ms). Hierarchical stepwise regression analysis predicting E/A ratio found gender (male > female) to be the best predictor (R (2 )= 0.09) followed by heart rate (R (2) increase = 0.07; total R (2 )= 0.15; p < 0.01) and by RWT (R (2) increase = 0.05; total R (2 )= 0.21; p < 0.015). For IVRT prediction, gender (male > female) was the best predictor (R (2 )= 0.11), followed by total peripheral resistance (R (2) increase = 0.06; total R (2 )= 0.17; p < 0.017). CONCLUSION: The study data indicate that gender differences in diastolic function exist already in youth. Girls show a higher RWT, a lower E/A ratio, and a shorter IVRT. The implications of these differences for cardiovascular morbidity and mortality of the two genders require attention.

Urinary excretion of vasoactive factors are correlated to sodium excretion.

BACKGROUND: The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in humans. PROCEDURE: Excretion rates of sodium, nitrates/nitrites (NOx), cGMP, and endothelin-1 (ET-1) were measured before and after ingestion of a mixed electrolyte solution (8 oz Gatorade) while undergoing a routine cardiovascular evaluation in a sample of 51 normotensive young adults. RESULTS: Significant correlations were detected for changes in excretion between all four variables, r ranged from 0.50 to 0.86 (P < .001). Correlations were higher in African Americans than white Americans. CONCLUSIONS: The association of renal ET-1 and NO activity with sodium excretion supports the hypothesis that these factors play a role in the physiologic response to acute changes in sodium intake, particularly in African Americans.

Racial differences in the influence of body size on ambulatory blood pressure in youths.

BACKGROUND: African Americans have higher night-time blood pressures than Caucasians do despite their having similar daytime blood pressures. It is well established that body size is related to casual blood pressure. OBJECTIVE: To examine the influence of body size on racial differences in patterns of ambulatory blood pressure. METHODS: Ambulatory blood pressure recordings were performed on 292 healthy children and adolescents (148 African Americans and 144 Caucasian) aged 10-18 years (mean 13+/-2 years). These blood pressures were related to height, weight, body surface area, and body mass index in separate regression models that also included race, sex, and age as factors. RESULTS: The race-by-height interaction was significant for night-time systolic blood pressure (P<0.02), with a significant relationship for African Americans (P<0. 0001), but not for Caucasians. The race-by-weight interaction was significant for night-time systolic blood pressure (P<0.04), also with a greater relationship for African Americans (P<0.0001) than for Caucasians (P<0.03). In addition, the race-by-weight interaction was significant for night-time diastolic blood pressure (P<0.04), with a significant relationship for African Americans (P<0.01), but not for Caucasians. Finally, the race-by-body-surface-area interaction was significant for night-time diastolic blood pressure (P<0.05), again with a significant relationship for African Americans (P<0.02) but not for Caucasians. CONCLUSION: Differences in the relationship between body size and blood pressure contribute to the racial differences in patterns of ambulatory blood pressure and should be considered when evaluating patterns of blood pressure in African American youths.

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 ambulatory blood pressure monitoring-derived 24 h patterns of blood pressure in adolescents.

BACKGROUND: Many pathologic conditions are characterized by a blunted nocturnal decline in blood pressure. OBJECTIVE: To review the evidence that African Americans display a similar pattern and examine factors associated with the pattern. METHOD: We reviewed published racial comparisons of patterns of ambulatory blood pressure in adults and youths. RESULTS: Authors of 15 studies reported finding blunted nocturnal declines in African Americans and authors of two studies did not. Authors of studies of Africans in Africa and of blacks from other countries reported normal nocturnal declines. Both intake of sodium and indexes of body size have been related to nocturnal blood pressure in African-American youths. This pattern is related to greater than normal target-organ changes. CONCLUSION: ; We conclude that the race of a patient should be considered when evaluating a 24h pattern of blood pressure in an adolescent; and the blunted nocturnal decline displayed by many African-American adolescents is the result of a gene-environment interaction and therefore is susceptible to modification through changes in diet, level of activity, and other environmental factors.

Temporal stability of ambulatory blood pressure and heart rate in youths.

BACKGROUND: The use of ambulatory blood pressure monitoring for pediatric populations is increasing. OBJECTIVE: ; To determine the 2-year stability of ambulatory blood pressure in youths. METHODS: We evaluated 2-year stabilities of resting and ambulatory blood pressures in 197 youths (aged 13.9+/-2.3 years at initial evaluation). Readings were taken every 20 min during the daytime (0800-2200 h) and every 30 min at night (0000-0600 h). RESULTS: Daytime and night-time systolic blood pressure increased (P < 0.01 for both) as did resting systolic blood pressure (P < 0.05). Measures of diastolic blood pressure did not change. Changes in systolic blood pressure were related to changes in body size. Estimates of stability for resting and ambulatory measurements were similar, ranging from 0.65 to 0.75. In addition, correlation coefficients for relationships between first and second readings for resting and ambulatory measurements were similar ranging from 0.43 and for resting heart rate to 0.72 for 24h systolic blood pressure (P < 0. 001 for each). The only significant correlation between change scores for resting and ambulatory values was that between resting and night-time diastolic blood pressures (r = 0.33, P < 0.001). CONCLUSION: Measures of blood pressure derived from ambulatory blood pressure monitoring reflect changes in blood pressure in youths at least as well as do changes in resting blood pressure despite the high degree of variability in levels of physical activity and affective states of the children during the ambulatory recordings.

Predictors of future ambulatory blood pressure in youth.

OBJECTIVE: The objective of this study was to determine the predictors of future ambulatory blood pressure in normotensive youths with family histories of essential hypertension. STUDY DESIGN: Eighty-eight healthy youths (mean age 10.9 +/- 2.5 years; 52 blacks, 36 whites; 45 boys) were studied. During an initial visit anthropometric variables and hemodynamics were measured at rest and before, during, and after three laboratory stressors: postural change, forehead cold, and video game challenge. The subjects' ambulatory blood pressure was monitored for 24 hours as part of a follow-up evaluation an average of 2.5 years later. RESULTS: Anthropometric and demographic variables and measures of reactivity to laboratory stressors were related to future daytime and nighttime ambulatory blood pressure. CONCLUSION: These findings provide important information on the predictors of ambulatory blood pressure and underscore the importance of resting blood pressure and adiposity. These results support the guidelines of the Second Task Force, which recommend the measurement of blood pressure and adiposity in the context of ongoing health care.

Stress hypertension: the "wrong" genes in the "wrong" environment.

Jim Henry demonstrated an animal's society can induce an increase in blood pressure and its cardiovascular sequale. He recognized that the stress required to elevate blood pressure was a function of the genetically determined behavioral traits of the mice used. He termed some strains aggressive, others peaceable. Being highly inbred (indeed isogenic strains) it was intriguing to find that the behavior of these genetically identical individuals could differ markedly once placed in a society that decreased territory. A dominant or "king" mouse emerged. Other non-dominant males were aggressive and striving to be king. Adrenal medullary systems were activated and renins high. Others huddled in one cage and appeared to have given up. Jim called them depressed. Their adrenal cortex was hyperplastic suggesting pituitary adrenal axis activation as in depression, their renin was low and corticosterone high. In rats, careful selection of a strain genetically aggressive had to be combined with titration of societal stress to reliably induce hypertension. Its likely that humans retain some, if not all, of these variations, i.e. some respond to stress with an increase in blood pressure and others do not, some respond via the sympathetic pathway and others by adrenal cortical activation. The suggestion that African American's high blood pressures is due to stress is relevant to the Henry paradigm and the known genetic influences on sodium retention in blacks. The integration of this paradigm with the genetically increased sensitivity to the blood pressure raising effects of dietary sodium in blacks is proposed and discussed.

Genetic influences on ambulatory blood pressure patterns. The Medical College of Virginia Twin Study.

The genetic influence of ambulatory blood pressure and heart rate was examined in 38 pairs of monozygotic twins, 17 pairs of same-sex dizygotic twins, and 11 pairs of opposite-sex dizygotic twins, all aged 15 or 17 years. The data were analyzed taking into consideration that the response was multivariate (24-h values) instead of the usual univariate response. The results demonstrated the heritability of ambulatory blood pressure and heart rate. This was true regardless of whether the estimate of heritability involved monozygotic twin pairs compared to same-sex dizygotic twin pairs only, or all dizygotic twin pairs. The time-related intraclass correlation coefficient within each twin classification indicated that the patterns of response within twin pairs correlated more for monozygotic twin pairs than within twin pairs for either set of dizygotic twin pairs. In addition, although the opposite-sex dizygotic twin pairs may have different mean levels of response, they exhibit a similarity of patterns of response akin to that seen within same-sex dizygotic twin pairs.

Racial differences in the age-related increase in left ventricular mass in youths.

We determined the factors related to left ventricular mass adjusted for body size in 60 black (mean age, 13 +/- 2 years) and 40 white (mean age, 14 +/- 2 years) normotensive youths. The factors examined included age, sex, systolic blood pressure, diastolic blood pressure, plasma renin activity, plasma aldosterone concentration, and sodium and potassium intake as determined by 24-hour excretion. Sex (beta = 13.3, P < .003), age (beta = 2.88, P < .001), and systolic blood pressure (beta = 0.41, P < .02) were independent predictors in the sample as a whole, accounting for 37% of the variance of left ventricular mass adjusted for height. Separate analyses were performed for black and white subjects. In the black subjects, age (beta = 4.4, P < .004) followed by sex (beta = 11.85, P < .02) were independent factors, accounting for 43% of the variance of left ventricular mass adjusted for height. In contrast, in white subjects systolic blood pressure (beta = 0.4, P < .003) followed by sodium excretion (beta = 0.13, P < .05) were independent factors, with gender (beta = 8.89, P < .07) tending to account for 36% of the variance. Similar results were observed for left ventricular mass adjusted for body surface area. In conclusion, the age-related increase in adjusted left ventricular mass in black but not white youths may in part account for the early development of cardiovascular disease among the black population.

Ambulatory blood pressure recordings in children and adolescents.

OBJECTIVE: To provide reference data for ambulatory blood pressure monitoring (ABPM) and to determine the influence of age, sex, and race on these values. METHODS: ABPM was performed on 300 healthy, normotensive boys and girls between the ages of 10 and 18 years, including 160 boys and 140 girls, of whom 149 were white and 151 were black. Mean systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) while awake and during sleep were calculated for black and white boys and girls aged 10 to 12 years, 13 to 15 years, and 16 to 18 years. RESULTS: Boys compared with girls 10 to 12 years of age had higher mean (+/- SD) SBP (115 +/- 9 vs 112 +/- 9 mm Hg; P < .01) and DBP (67 +/- 7 vs 65 +/- 5 mm Hg; P < .01) while awake. Boys compared to girls 13 to 15 years of age had higher SBP while awake (116 +/- 11 vs 112 +/- 8 mm Hg; P < .01). Boys compared with girls 16 to 18 years of age had higher SBP while awake (125 +/- 12 vs 111 +/- 9 mm Hg); P < .01) and during sleep (116 +/- 11 vs 106 +/- 9 mm Hg). Comparisons within sex showed similar changes with age for boys and girls. Blacks compared with whites 13 to 15 years of age had higher SBP during sleep (109 +/- 11 vs 105 +/- 10 mm Hg; P < .01), and blacks compared with whites 16 to 18 years of age had higher DBP during sleep (66 +/- 7 vs 58 +/- 6 mm Hg; P < .01). Comparisons across age groups within race showed that blacks 16 to 18 years of age had higher SBP during sleep than blacks 10 to 12 years of age (109 +/- 11 vs 104 +/- 10 mm Hg), and higher DBP during sleep (66 +/- 7 mm Hg; P < .01) than blacks 10 to 12 years of age (61 +/- 7 mm Hg; P < .01) and 13 to 15 years of age (61 +/- 8; P < .01 mm Hg). The changes with age were not significant for white subjects. CONCLUSION: These results provide age-specific reference data for ABPM in youths. These values differ by sex (boys more than girls) and race (Blacks more than Whites).

A Fourier series approach for comparing groups of subjects on ambulatory blood pressure patterns.

We develop an approach to the statistical analysis of 24-hour ambulatory blood pressure monitoring where we represent each subject's profile by a different mathematical model. We first smooth the data and then use a Fourier series approach to determine the best model for each subject. We then estimate summary variables based on each subject's model to compare distinct groups of subjects. In comparing 15 adult black male hypertensives to eight adult black male normotensives we found that the two groups differ on the shift away from the mesor for both the systolic and the diastolic blood pressure profile.

Ambulatory blood pressure and renal function in healthy children and adolescents.

Our previous studies using noninvasive ambulatory blood pressure (ABP) monitoring demonstrated racial differences in the diurnal pattern of blood pressure (BP), with higher nighttime BP for African-Americans than for Anglo-Americans despite similar daytime BP. We have hypothesized that the increased BP load in African-Americans contributes to the increased prevalence of hypertension and BP-induced target organ damage in adults. The purpose of this study was to examine the relationship between ABP patterns and renal function in healthy, normotensive black and white youths. The subjects were 22 African-American and 28 Anglo-American children and adolescents aged 10 to 18 years. Renal function was estimated by creatinine clearance (CCr). The African-American and Anglo-American subjects were similar in age, gender composition, casual BP, and CCr. The relationship between CCr and BP was not significant for casual BP or daytime BP for either group, or with nighttime BP in the Anglo-American subjects. In contrast, CCr was related negatively to both nighttime systolic BP (r = -0.47, beta = -1.21; P < .02) and nighttime diastolic BP in the African-American subjects (r = -0.45, beta = -2.13; P < .03). These results are consistent with our hypothesis.

Ambulatory blood pressure patterns in youth.

We examined the influence of sex, race, and age on ambulatory blood pressure (BP) patterns in youths. The subjects were 300 normotensive, healthy adolescents between the ages of 10 and 18 years, including 160 boys and 140 girls, of whom 149 were white and 151 were black. The data were divided into periods of activity (Period I: 8 AM to 10 PM) and inactivity (Period II: 10 PM to 8 AM). Boys had higher systolic BP during both Period I (117 +/- 11 nu 112 +/- 8 mm Hg; P < .05) and Period II (109 +/- 11 nu 106 +/- 10 mm Hg; P < .03). Blacks had higher systolic (108 +/- 10 nu 106 +/- 10 mm Hg; P < .01) and diastolic BP (63 +/- 8 nu 60 +/- 7 mm Hg; P < .003) during Period II. Interactions between race and age were found for both systolic (P < .005) and diastolic (P < .005) BP during Period II. Further analyses indicated associations between age and both systolic (beta = 1.16; P < .001) and diastolic (beta = 1.04; P < .0001) BP in black but not white subjects. An interaction was observed between sex and age for systolic BP during Period II (P < .005), with a relationship for boys (beta = 1.47; P < .001) but not for girls. These results suggest that the black adolescents showed a progressive increase in nocturnal BP with age, a pattern not observed in the white youths. This increased BP load may contribute to the early development of hypertension and BP-induced target organ damage in blacks.

Renin-angiotensin-aldosterone system in healthy subjects aged ten to eighteen years.

We obtained normative data for plasma renin activity (PRA) and plasma aldosterone concentration from a biracial sample of 195 healthy, normotensive children and adolescents aged 10 to 18 years. The sample included 119 boys and 76 girls, of whom 103 were black and 92 were white. The mean PRA value (+/- SD) was 2.52 +/- 1.95 ng/ml per hour, with minimal and maximal values of 0.1 and 13.50 ng/ml per hour. The mean plasma aldosterone concentration was 12.56 +/- 8.59 ng/ml, with minimal and maximal values of 1.6 and 50.1 ng/ml. We also examined the effects of subject characteristics and electrolyte intake. The slope relating sodium excretion to PRA was negative and highly significant (slope = -0.01; p < 0.003). The slope relating PRA to plasma aldosterone concentration was positive and highly significant (slope = 1.59; p < 0.0001). We did not observe differences in either variable as a function of age, sex, race, or family history of hypertension. These results suggest that differences based on race and family history of hypertension observed in adults are not present in youth.

Sodium excretion and racial differences in ambulatory blood pressure patterns.

The influence of Na+ excretion and race on casual blood pressure and ambulatory blood pressure patterns was examined in a biracial sample of healthy, normotensive children and adolescents (10-18 years; n = 140). The slopes relating 24-hour urinary Na+ excretion to systolic blood pressure were different for both black and white subjects for casual blood pressure (p less than 0.001) and blood pressure during sleep (p less than 0.03). For casual blood pressure, the slope was significant for black subjects (beta = 0.17; p less than 0.001) but not for white subjects. For blood pressure during sleep, the slope was again significant for black subjects (beta = 0.08; p less than 0.01) but not for white subjects. Na+ excretion was also related to awake levels of systolic blood pressure for black subjects (beta = 0.08, r = 0.36; p less than 0.01), although the slopes for both black and white subjects were not significantly different. Further analyses indicated the results were not due to racial differences in 24-hour urinary K+ excretion. However, plasma renin activity was marginally related to Na+ excretion in white subjects (r = 0.22; p less than 0.06) but not black subjects, a finding that is consistent with previous studies. Na+ excretion was not associated with diastolic blood pressure or heart rate in either group under any condition. The results of this study support research that has demonstrated a stronger relation between Na+ handling and casual blood pressure in black subjects and extend these findings to blood pressure while the subject is both awake and asleep.

Patterns of sodium excretion during sympathetic nervous system arousal.

The purpose of this study was to examine Na+ handling and regulation during 1 hour of behaviorally induced sympathetic nervous system (SNS) arousal followed by 2 hours of recovery. Two patterns of response were observed among experimental subjects, despite similar changes in blood pressure and heart rate. In one group (n = 19), Na+ excretion increased significantly during SNS arousal, which then decreased significantly during recovery (12.3 versus 16.0 versus 13.1 meq/hr, baseline, SNS arousal, recovery, respectively). Changes in Na+ excretion were correlated with changes in creatinine clearance from baseline to SNS arousal (r = 0.54) and SNS arousal to recovery (r = 0.58), and were accompanied by significant increases in plasma renin activity (1.5 versus 2.0 ng/ml/hr) and aldosterone (8.5 versus 10.3 ng/ml/hr) from baseline to SNS arousal. Na+ excretion decreased during SNS arousal in the other group of subjects (n = 17) and remained below baseline levels during recovery (16.2 versus 12.7 versus 11.9 meq/hr). These changes were associated with significant decreases in creatinine clearance from baseline to recovery (138 versus 121 ml/min/1.73 m2) and significant increases in plasma renin activity from baseline to SNS arousal (1.3 versus 2.2 ng/ml/hr) but not in aldosterone. Control subjects (n = 24) maintained baseline levels of each variable throughout the procedure. These results suggest that individuals differ in Na+ handling and regulation during behavioral arousal. Decreases in Na+ have been reported previously in humans and animals at risk for the development of hypertension.