The renin-angiotensin aldosterone system and osteoporosis: findings from the Women's Health Initiative.

New users of RAAS inhibitors, including ACE inhibitors and ARBs, have a small increased risk for fracture in the first 3 years of use, with a reduced risk of fracture with longer duration of use. INTRODUCTION: Pharmacological inhibitors of the renin-angiotensin aldosterone system (RAAS) are used to treat hypertension. However, the relationship of these medications to osteoporosis is inconsistent, and no study has included simultaneous measurements of both incident fractures and bone mineral density (BMD). METHODS: The association of RAAS inhibitor use (n = 131,793) with incident fractures in new users of these medications in women in the Women's Health Initiative over a minimum median follow-up of 6.5 years was assessed by Cox proportional hazard models. The association of incident fractures by a cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated. Subgroup analysis of fracture risk by RAAS inhibitor use confined to women with hypertension was also performed (n = 33,820). The association of RAAS inhibitor use with changes in BMD of the hip was estimated by linear regression in 8940 women with dual energy X-ray absorptiometry measurements. RESULTS: There was no significant association between RAAS inhibitor use and all fractures in the final adjusted multivariable models including hip BMD (HR 0.86 (0.59, 1.24)). However, among users of RAAS inhibitors, including ACE inhibitors and angiotensin receptor blockers (ARBs), hazard ratios for all incident fracture sites in final multivariable models including hip BMD showed dramatic differences by duration of use, with short duration of use (3 years or less) associated with a marked increased risk for fracture (HR 3.28 (1.66, 6.48)) to (HR 6.23 (3.11, 12.46)) and use for more than 3 years associated with a reduced fracture risk (HR 0.40 (0.24, 0.68) to (HR 0.44 (0.20, 0.97)) . Findings were similar in the subgroup of women with a history of hypertension. There was no significant change in BMD of the hip by RAAS inhibitor use. CONCLUSIONS: In postmenopausal women, use of RAAS inhibitors, including ACE inhibitors and ARBs, is associated with an increased risk for fracture among new users of these medications in the first 3 years of use. However, long-term use (> 3 years) is associated with a reduced risk. Consideration for fracture risk may be part of the decision-making process for initiation of these medications for other disease states.

Body mass index trajectories in childhood is predictive of cardiovascular risk: results from the 23-year longitudinal Georgia Stress and Heart study.

The childhood high body mass index (BMI) is associated with cardiovascular risk, but the association between childhood BMI trajectory patterns and cardiovascular risk remains unclear. The purposes of this study are to identify subgroups of individuals with similar trajectories in BMI during childhood, and to determine the relationship of childhood BMI trajectories with subclinical cardiovascular disease in young adulthood, indexed by intima-media thickness (IMT) and left ventricular mass index (LVMI). The participants were from the Georgia Stress and Heart (GSH) study. A total of 626 participants with BMI measured 3-12 times during childhood (5-18 years old) were included. By using latent class models, three trajectory groups in BMI were identified, including high increasing (HI), moderate increasing (MI) and normal group. We found that childhood trajectory of BMI was significantly associated with IMT and LVMI in young adulthood even after adjustment for BMI in young adulthood. Our results suggested that different BMI trajectory patterns exist during childhood. We for the first time reported the association between childhood BMI trajectory patterns and subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BMI from childhood may help to identify a high cardiovascular risk population in early life.

Race/ethnicity determines the relationships between oxidative stress markers and blood pressure in individuals with high cardiovascular disease risk.

Oxidative stress (OS) and cardiovascular (CV) reactivity are related to CV morbidity and mortality. However, little is known about the relationships between these CV risk factors and their confounders. We hypothesize that higher OS is linked to higher blood pressure (BP) reactivity to acute laboratory stressors and in the natural setting. We studied 137 subjects with a family history of hypertension and early myocardial infarction. There were 63 European Americans (EAs) (38 males) and 74 African Americans (AAs) (35 males), aged 19-36 (27.6±3.1). The protocol included a competitive video game, cold stressor and ambulatory BP recording. Blood samples were drawn six times for OS markers (8-hydroxydeoxyguanosine (8-OHdG) and 8-Isoprostane) assay. Repeated measures analyses of covariance were used to test for mean differences and Pearson correlations were used to test OS and BP associations. There were no significant race/ethnicity differences in BP reactivity to either stressor (both P's>0.48). 8-OHdG levels were significantly lower across all time points for AAs than for EAs (P<0.05), while levels of 8-isoprostane did not differ significantly (P>0.10). Averaged 8-OHdG levels significantly correlated with systolic blood pressure (SBP) reactivity (r=0.45, <0.01) and 24-h, daytime and nighttime SBP (r range=0.37-0.42, all P's<0.02) for EAs but not for AAs, whereas 8-isoprostane levels were significantly correlated with reactive SBP and nighttime diastolic blood pressure (DBP) (both r's=0.38, P<0.01) for AAs but not for EAs. These findings suggest a link between OS and BP changes in subjects at high risk for CV disease (CVD). Further, race/ethnicity determines which OS marker will impact BP variation implying race/ethnicity differences in OS-related mechanisms of CVD.

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.

Volatile organic compound measurements in the California/Mexico border region during SCOS97.

Measurements of volatile organic compounds (VOC) were carried out in the California/Mexico border region during the Southern California Ozone Study in the summer of 1997 (SCOS97). Integrated 3-h samples were collected in Rosarito (south of Tijuana, Mexico) and in Mexicali during intensive operational periods (IOP), twice per IOP day. VOC were collected using stainless-steel 6-1 canisters; carbonyl compounds were collected using 2,4-dinitrophenyl-hydrazine (DNPH) impregnated C18 SepPak cartridges. The canister samples were analyzed for speciated volatile hydrocarbons (C2-C12), CO, CO2, CH4, methyl t-butyl ether (MTBE), and halogenated hydrocarbons. DNPH-impregnated cartridges were analyzed for 14 C1-C7 carbonyl compounds. The concentrations of all species were higher at Mexicali than in Rosarito. A good correlation between total non-methane hydrocarbons (TNMHC), CO, and other pollutants associated with motor vehicle emissions observed for Mexicali indicates that the main source of TNMHC at this site is vehicular traffic.

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.

Arizona hazardous air pollutants monitoring program

In order to evaluate the existing risk to public health in Arizona related to hazardous air pollution, ambient air monitoring for selected hazardous air pollutants (HAPs) was carried out in 1994-1996 in several representative urban and rural areas of Arizona. A wide range of organic HAPs was monitored, requiring a variety of sampling and analysis methods. Stainless steel SUMMA canisters were used for collection of volatile hydrocarbons and halocarbons, which were analyzed by capillary gas chromatography with flame ionization and electron capture detection (GC-FID/ECD). Carbonyl compounds were collected using 2,4-dinitrophenylhydrazine-impregnated cartridges and analyzed by high performance liquid chromatography with ultraviolet detection. Semi-volatile and non-volatile polycyclic aromatic compounds were collected using a sampling train consisting of a filter followed by a PUF/XAD-4/PUF sandwich cartridge. Following extraction, samples were analyzed by capillary GC with mass spectrometric detection (GC-MS). Database software was developed for data processing and reporting functions. This paper describes the sampling strategy and the sampling and analysis methods employed in the monitoring program and presents a summary of all the results obtained during the duration of the sampling program.

Plasma renin activity is associated with bone mineral density in premenopausal women.

Bone mineral density (BMD), plasma renin activity (PRA) and dietary calcium and sodium were evaluated in 47 Caucasian premenopausal women. All subjects were free of any disorder or medications known to affect calcium or bone metabolism. Those subjects with low PRA (< 1.3 ng/ml) had 4.3% lower BMD at the distal radius (p = 0.03). Other skeletal sites appeared to have lower BMD in subjects with low PRA but these differences were not statistically significant. There was a tendency for the low PRA group to have a lower dietary intake of calcium (p = 0.06) as compared with the normal PRA group (> or = 1.3 and < 4.0 ng/ml). Positive correlations were found between calcium intake and PRA (r = 0.26, p = 0.09); and between calcium/sodium intake and distal radial BMD (r = 0.31, p = 0.04), mid-radial BMD (r = 0.30, p = 0.04), total hip BMD (r = 0.23, p = 0.12) and total body BMD (r = 0.27, p = 0.07). This study provides preliminary evidence that a sodium intake > 3400 mg/day, as evidenced by the suppression of PRA, may affect bone mass and the effect may be modified by the level of calcium intake. Additional research is needed to replicate our findings with a larger sample size.

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.