Jerome H. Markovitz

Cardiovascular reactivity to video game predicts subsequent blood pressure increases in young men: The CARDIA study:

Objective This study was undertaken to determine the relationship between heightened reactivity of blood pressure (BP) during stress and 5-year changes in blood pressure and hypertensive status, using the CARDIA study. Method A total of 3364 participants (910 white men, 909 white women, 678 black men, and 867 black women), initially 20 to 32 years old and normotensive, were included. Cardiovascular reactivity to psychological stressors (video game and star-tracing tasks for 3 minutes, cold pressor test for 1 minute) was measured in 1987-1988. We then examined reactivity as a predictor of significant BP change (>or=to8 mm Hg, thought to represent a clinically significant increase) over the next 5 years. Logistic regression models were used to control for potential covariates. Significant BP change and the development of hypertension (BP greater than 140/90 or taking medication for hypertension) over the 5-year follow-up were examined in separate analyses. Results Increased systolic blood pressure (SBP) reactivity to the video game was associated with a significant 5-year SBP increase among the entire cohort, independent of resting SBP (p < .0001). Subsequent analyses showed that this relationship held for men but not for women. Reactivity to the star-tracing task or the cold pressor test did not predict significant BP change. Among black men only, new hypertensives (N = 36) had greater diastolic blood pressure (DBP) reactivity to the video game (p = .01). Conclusions: Although BP reactivity to all physical and mental stressors used in this study did not consistently predict 5-year change in BP in this young cohort, the results indicate that reactivity to a video game stressor predicts 5-year change in BP and early hypertension among young adult men. These findings are consistent with other studies showing the usefulness of stressors producing a primarily beta-adrenergic response in predicting BP change and hypertension. The results may be limited by the shortened initial rest and recovery periods used in the CARDIA protocol.

Psychological, biological and health behavior predictors of blood pressure changes in middle-aged women.

A long-standing hypothesis is that feelings of anger and anxiety increase the risk for essential hypertension. Most studies examining this hypothesis have been cross-sectional in design or undertaken with men only. We tested this hypothesis along with determination of the other behavioral and biological predictors of increases in systolic (SBP) and diastolic (DBP) blood pressure from baseline to a follow-up examination 3 years later in a prospective study of 468 middle-aged women whose blood pressure at the baseline examination was less than 140/90 mmHg. Analyses showed that increases in the Spielberger Trait Anger Scale between the baseline and 3-year follow-up examination, as well as Framingham Tension scores (a measure of anxiety) at baseline, independently predicted an increase in SBP (P less than 0.01). Other factors that independently predicted an increase in SBP were baseline fasting insulin, parental history of hypertension and increases in body mass index and in alcohol intake across the 3 years of follow-up. Increases in the Spielberger Trait Anger Scores independently predicted increases in DBP (P less than 0.02), as did black race, increases in body mass index and hematocrit and decreases in potassium intake. Although menopausal status and hormone replacement therapy were unrelated to changes in blood pressure, postmenopausal women on hormone replacement therapy did show significant increases in DBP in the univariate analysis. Anxiety at baseline, along with parental history of hypertension, baseline fasting insulin and baseline body mass index, predicted a later onset of hypertension, i.e. on pharmacologic treatment for hypertension, in the univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hostility on platelet reactivity to psychological stress in coronary heart disease patients and in healthy controls.

Previous studies have demonstrated a potential relationship between psychological stress and platelet activation, which may serve as a link between stress and myocardial infarction (MI).However, the possibility that personality traits associated with coronary heart disease may affect platelet activation has not been adequately investigated. The effect of a laboratory stressor (Type A Structured Interview (SI) and speech task) on platelet activation was assessed in 14 stable post-MI patients and 15 age-matched healthy men, using a standardized method of measuring plasma beta-thromboglobulin (BTG) levels. BTG levels were increased after the stressor (average change = 2.0 ng/ml, p =.005). Increases in BTG with stress were related to higher SI ratings of Potential for Hostility (r =.53, p =.004) and Type A behavior (r =.43, p =.02) but not to Cook-Medley-rated hostility scores. Increases in norepinephrine levels and in diastolic blood pressure were nonsignificantly related to increases in BTG levels (ps <.10), whereas increases in epinephrine levels were unrelated. Despite ceasing aspirin and other platelet inhibitors for 10 days before testing, individuals taking platelet inhibitors before the study had less change in BTG with stress (p =.05). However, after statistical adjustment for this factor, SI ratings of Potential for Hostility were still strongly related to increases in BTG with stress (adjusted r =.56, p =.002). Contrary to expectations, healthy men tended to have greater change in BTG with stress than post-MI patients (p =.06). These results indicate that acute stress increases BTG levels and that hostility is related to greater platelet reactivity, independent of any long term effects of platelet inhibition.

Increased Prevalence of Smaller and Denser LDL Particles in Asian Indians

There is increasing evidence to believe that Asian Indians are at an increased risk of coronary heart disease (CHD), which cannot be attributed to the common risk factors. Individuals with small, dense LDL phenotype are also known to be at increased risk of CHD. Our objective was to examine whether the prevalence of smaller and denser LDL particles is increased in Asian Indians. Thirty-nine Asian Indians (22 men and 17 women), aged 25 to 45 years, were matched with 39 whites for age and gender. Cholesterol profiles of lipoprotein classes and LDL subclasses were measured using the Vertical Auto Profile-II (VAP-II) and LDL-VAP-II methods, respectively. Six LDL subclasses (LDL1 to LDL6) have been identified using the LDL-VAP-II, with LDL1 and LDL6, respectively, being the most and least buoyant subclasses. The prevalence of small, dense LDL type (subjects with major LDL subclass 5 or 6) was significantly higher in Asian Indians compared with white subjects (44% versus 21%; P<0.05). The relative position of the major LDL density peak (LDL-Rf) on 0 to 1 scale in LDL-VAP-II density gradient was also significantly decreased in Asian Indians (0.462+/-0.076 versus 0. 505+/-0.086; P<0.02), suggesting an increased LDL density. Furthermore, this increased prevalence of small, dense LDL type appears to be due to the increased triglycerides (TG) (r for LDL-Rf versus TG=0.681, P<0.001), with fasting insulin being one of the important determinants of TG (r for TG versus fasting insulin=0.572, P<0.001). In addition, fasting insulin was significantly increased in Asian Indians with small, dense LDL type compared with other Asian Indians, suggesting a significant role of insulin resistance in increasing the prevalence of small, dense LDL type. We conclude that the increased prevalence of small, dense LDL observed in Asian Indians might contribute to their increased CHD risk.

Hostility Is Associated With Increased Platelet Activation in Coronary Heart Disease

Objective To determine whether Potential for Hostility is related to platelet activation (PA) among patients with coronary heart disease (CHD) and healthy controls. Increased PA has been associated with adverse secondary events after myocardial infarction or coronary angioplasty. Methods We tested 32 CHD patients and 23 healthy men and women, aged 45 to 73 years, for PA by using whole blood flow cytometry. PA was measured in blood exiting a bleeding time wound (wound-induced platelet activation) and also in venous blood stimulated in vitro with collagen. Monoclonal antibodies were used to test for fibrinogen receptor activation and fibrinogen receptor binding. All subjects refrained from taking aspirin for at least 14 days before testing; CHD patients stopped nitrates and calcium channel blockers for 24 hours, while continuing to take lipid-lowering medications. Potential for Hostility was assessed, using the Type A Structured Interview. Results Among the CHD patients only, all four of the wound-induced fibrinogen receptor activation indicators (activation and binding) were related to hostility; the relationships were significant for receptor activation at 2 minutes, and for receptor binding at 1 minute (r values = .46, p values = .02). Subjects on lipid-lowering medications had lower PA for most measures. Healthy subjects had higher wound-induced fibrinogen receptor activation at 2 minutes and fibrinogen receptor activation in vitro than the CHD patients (p = .04), but after statistical adjustment for lipid-lowering medications, there were no significant differences between the patients and controls. Conclusions PA was related to hostility among CHD patients, consistent with previous studies indicating a relationship between PA and psychological factors among CHD patients. However, PA was not increased in nonsmoking, nondepressed CHD patients relative to controls.

Reactivity as a Predictor of Subsequent Blood Pressure: Racial Differences in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract—This study investigated the association between cardiovascular reactivity and subsequent ambulatory blood pressure in 316 black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Cardiovascular laboratory reactivity was examined in subjects 20 to 33 years old, and ambulatory blood pressure and heart rate were measured 3 years later. Average ambulatory pressure during a 24-hour period was regressed separately on stress reactivity and standard covariate risk factors in each race/gender subgroup. Blacks had higher blood pressure and heart rates than whites, men had higher blood pressure than women, and women had higher heart rates than men. After controlling for age, baseline systolic pressure, familial history of hypertension, smoking, alcohol consumption, body mass index, and exercise, systolic blood pressure reactivity to star tracing and cold pressor stress were significantly associated with systolic ambulatory pressure in black men and women 3 years later (partial r =0.24 to 0.37). Heart rate reactivity to video challenge and star tracing were also significantly predictive of subsequent ambulatory heart rate in blacks. Diastolic star tracing reactivity was significantly associated with subsequent ambulatory blood pressure in black women (r =0.23), and diastolic reactivity to video and star tracing were significantly predictive of ambulatory diastolic pressure in white men (r =0.39). We conclude that hyperresponsivity to stress may be a risk factor for subsequent blood pressure elevation in blacks and may be one pathway leading to the higher prevalence of hypertension in blacks than in whites.

Lack of Independent Relationships Between Left Ventricular Mass and Cardiovascular Reactivity to Physical and Psychological Stress in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

The objective of this study was to determine whether exaggerated blood pressure (BP) reactivity to stress and psychosocial characteristics are related to left ventricular mass (LVM) in a large cohort of young adults. Analyses were conducted with 3,742 participants of the CARDIA study (945 white men, 1,024 white women, 781 black men, and 992 black women), evaluated in 1990 to 1091 with echocardiographic measurement of LVM. Analyses were stratified by gender and race. The relationships of LVM/height2.7 and cardiovascular reactivity to physical and psychological stressors (treadmill exercise, cold pressor, video game, and star-tracing tasks), were examined in both univariate and multivariate analyses adjusting for baseline BP, weight, and other relevant biobehavioral variables. The relationships between LVM and several psychosocial characteristics (hostility, anger suppression, anxiety, depressive symptoms, and education) were also assessed. Systolic blood pressure (SBP) reactivity to exercise was significantly related to LVM in black and white men; LVM was 10% greater among white men with exaggerated (upper quintile) peak exercise SBP than among other white men. SBP reactivity to the cold pressor test was related to LVM in all race/gender groups, although the relationship remained significant only among white men and women in the multivariate analysis. Diastolic blood pressure (DBP) reactivity to the video game was related to LVM only among black men in adjusted analyses. After adjusting for resting BP, weight, and other covariates in linear multiple regression models, SBP reactivity to exercise explained only 3% of the variance in LVM among white men. Otherwise, reactivity to other stressors or psychosocial variables accounted for no more than 1% of the variance in LVM. It was concluded that among a cohort of young adults, blood pressure reactivity to physical and mental stressors did not add substantially to the prediction of LVM when resting BP, weight, and other covariates were taken into account.

Blood pressure responses to acute stress and left ventricular mass (The Hypertension Genetic Epidemiology Network Study)

Left ventricular (LV) hypertrophy is a major risk factor for cardiovascular morbidity. This study examined the extent to which exaggerated blood pressure (BP) reactivity is associated with LV mass and relative wall thickness (RWT) in a large sample of middle-aged hypertensive men and women. Participants included 1,012 African-Americans and 655 Caucasians recruited for the Hypertension Genetics Epidemiology Network (HyperGEN) study. A laboratory stress protocol was implemented, consisting of BP measurement during rest, handgrip, and a mental arithmetic stressor. This was followed by a 2-dimensional guided M-mode echocardiographic evaluation to measure LV mass. LV mass was greater among African-Americans relative to Caucasians (p <0.01). Systolic BP at rest was positively associated with LV mass and RWT in African-Americans (p <0.001) and in Caucasian women (p <0.0001). LV mass and RWT were compared in participants and participants were classified as high or low reactors based on their systolic BP responses to the 2 laboratory stressors. RWT demonstrated positive associations with systolic BP responses to both tasks. Associations with LV mass were mostly nonsignificant with the exception of a negative association in African-Americans between systolic BP responses to the arithmetic task and LV mass. We conclude that in this cohort of hypertensive middle-aged men and women, BP reactivity did not predict LV mass. Positive associations of systolic BP responses with RWT suggest that exaggerated reactivity may particularly be related to LV changes influenced by vascular tonus.

Increased Serotonin Receptor Density and Platelet GPIIb/IIIa Activation Among Smokers

This study sought to determine whether depressive symptoms and/or platelet serotonin receptor (5HT2A) density are associated with increased platelet activation (PA) found among smokers. Flow cytometric detection of PA was used to study 36 smokers and 16 nonsmokers, aged 18 to 48 years. Subjects were tested at baseline and after either smoking 2 cigarettes (smokers) or a similar resting interval (nonsmokers). Assessment of PA included both platelet secretion and fibrinogen receptor (GPIIb/IIIa) binding. Platelet 5HT2A receptor binding and saturation were tested using [3H]LSD, and depressive symptoms were measured using the Beck Depression Inventory. Platelet 5HT2A receptor density was increased among smokers versus nonsmokers (82.7+/-67.7 versus 40.0+/-20.2 fmol/mg protein; P<0.005), and there was a dose-dependent relationship between receptor density and packs/d among smokers. Baseline wound-induced GPIIb/IIIa binding at 1 minute and GPIIb/IIIa binding in response to collagen stimulation in vitro was increased among smokers (P<0.05); there were no changes in PA among smokers after smoking, and platelet secretion was not elevated among smokers. Depressive symptoms were associated with 5HT2A receptor density among nonsmokers (P<0.005), but no such relationship was evident among smokers; PA was unrelated to 5HT2A receptor density in either group. The findings indicate that smoking is associated with increased platelet serotonin receptor density and with increased GPIIb/IIIa receptor binding, although these 2 factors are not related to each other or to depressive symptoms among smokers. Serotonergic dysfunction may be an important factor in the development of cardiovascular disease among smokers.

Inverse relationship of urinary cyclic GMP to blood pressure reactivity in the CARDIA study: vasodilatory regulation of sympathetic vasoconstriction. Coronary Artery Risk Development in Young Adults.

Objective To determine whether urinary cyclic GMP (cGMP), which mediates the actions of the vasodilators nitric oxide and atrial natriuretic factor, is inversely related to blood pressure (BP) reactivity. In previous work, we found that urinary cGMP was inversely related to diastolic BP, but cGMP levels were higher among individuals presumed to have increased adrenergic activity, increased reactivity, and increased risk of hypertension (blacks, individuals with a family history of hypertension). Method We measured 24-hour urinary cGMP levels in a substudy of 529 individuals in the Coronary Artery Risk Development in Young Adults (CARDIA) study; the sample was 23 to 35 years of age and approximately balanced for race (black/white) and gender. BP reactivity to stressors (video game, star-tracing, cold pressor) was tested 3 years earlier. Baseline BP was included as a covariate in all analyses. Results Diastolic BP reactivity to cold pressor was inversely related to cGMP excretion (p < .05); the relationship was strongest among black women with a family history of hypertension (partial r = -.33, p < .01). Systolic BP reactivity to star-tracing was also inversely related to cGMP (p < .01); the relationship for both star-tracing and video game stressors was strongest among black men (partial r values = -.25 and -.24, respectively; p values < .01). Conclusions The results indicate that vasodilatory activity may impact the BP response to stress through modulation of adrenergic activation, particularly among blacks.