Gwendolyn A. Pincomb

Exaggerated pressure response to exercise in men at risk for systemic hypertension

Normotensive persons at high risk of developing systemic hypertension have greater cardiovascular reactivity to mental and physical stressors. This study compared cardiovascular responses to exercise in normotensive men (aged 28 +/- 0.8 years [mean +/- standard error of the mean]) at high risk (positive parental history and high normal resting blood pressure [BP], n = 20) and at low risk (negative history, low normal BP, n = 15) of hypertension. All men had normal body weight and exercise tolerance. During graded supine bicycle exercise, 35% (7 of 20) of high-risk men had exaggerated BP responses (greater than or equal to 230/100 mm Hg) versus 0% of low-risk men, thus forming 3 groups (low risk, high-risk normal BP response, high-risk exaggerated response). Cardiac function was measured by nuclear cardiography. Cardiac index, peripheral resistance index, left ventricular ejection fraction and contractility index were measured at rest and during each exercise work load. High-risk exaggerated responders could not be distinguished from their high-risk normal-responding counterparts using resting BP or other cardiovascular variables. During exercise all 3 groups had equivalent increases in cardiac output. However, the high-risk exaggerated responders had blunting in peripheral resistance decline, resulting in excessive BP increases. This finding suggests an impaired capacity for exercise-induced vasodilation, indicating that the exaggerated response group may be at highest risk for future hypertension in these 3 groups.

Effects of caffeine on vascular resistance, cardiac output and myocardial contractility in young men☆

The mechanisms by which caffeine typically elevates blood pressure (BP) in humans have not been previously examined using a placebo-controlled design. Accordingly, oral caffeine (3.3 mg/kg body weight, equivalent to 2 to 3 cups of coffee) was given on 2 days and a placebo was given on 1 day to 15 healthy young men using a double-blind, crossover procedure. All 3 test sessions were held during a week of caffeine abstinence. Multiple measurements were made on subjects at rest (baseline values) and over a 45-minute interval after ingestion of caffeine for BP, heart rate, systolic time intervals and thoracic impedance measures of ventricular function. Baseline measurements were highly reliable for each subject across all sessions and yielded means for placebo vs caffeine days that were not different. Caffeine increased systolic and diastolic BP (p less than 0.01) and decreased heart rate (p less than 0.05). The pressor effect was due to progressively increased systemic vascular resistance and resulted in greater stroke work (p less than 0.01). There was no indication that caffeine increased cardiac output or contractility. These actions of caffeine were replicable when each caffeine day was tested separately against the placebo day. These results suggest that caffeine use by persons with cardiovascular diseases should be examined to determine whether caffeines enhancement of vascular resistance may contribute to systematic hypertension and/or create excessive demands for cardiac work.

Hypertension Risk Status and Effect of Caffeine on Blood Pressure

We compared the acute effects of caffeine on arterial blood pressure (BP) in 5 hypertension risk groups composed of a total of 182 men. We identified 73 men with optimal BP, 28 with normal BP, 36 with high-normal BP, and 27 with stage 1 hypertension on the basis of resting BP; in addition, we included 18 men with diagnosed hypertension from a hypertension clinic. During caffeine testing, BP was measured after 20 minutes of rest and again at 45 to 60 minutes after the oral administration of caffeine (3.3 mg/kg or a fixed dose of 250 mg for an average dose of 260 mg). Caffeine raised both systolic and diastolic BP (SBP and DBP, respectively; P<0.0001 for both) in all groups. However, an ANCOVA revealed that the strongest response to caffeine was observed among diagnosed men, followed by the stage 1 and high-normal groups and then by the normal and optimal groups (SBP F(4),(175)=5.06, P<0.0001; DBP F(4,175)=3.02, P<0.02). Indeed, diagnosed hypertensive men had a pre-to-postdrug change in BP that was >1.5 times greater than the optimal group. The potential clinical relevance of caffeine-induced BP changes is seen in the BPs that reached the hypertensive range (SBP >/=140 mm Hg or DBP >/=90 mm Hg) after caffeine. During the predrug baseline, 78% of diagnosed hypertensive men and 4% of stage 1 men were hypertensive, whereas no others were hypertensive. After caffeine ingestion, 19% of the high-normal, 15% of the stage 1, and 89% of the diagnosed hypertensive groups fell into the hypertensive range. All subjects from the optimal and normal groups remained normotensive. We conclude that hypertension risk status should take priority in future research regarding pressor effects of dietary intake of caffeine.

Heart rate reactivity as a predictor of neuroendocrine responses to aversive and appetitive challenges.

&NA; The present paper examines the neuroendocrine influences of aversive and reward incentives (noise and shock versus monetary bonuses) presented during reaction time tasks administered to 71 healthy men (ages 21 to 35) classified as being high (N = 30) or low (N = 41) in heart rate reactivity. High heart rate reactivity was defined as a peak heart rate increase or greater than 19 bpm to a cold pressor test administered on a different day. Independent groups of subjects worked on one of two visual reaction time tasks: either to avoid exposure to noise (115‐dBA bursts) and shock (3.5 mV, 2 sec), or to earn monetary bonuses (

Borderline hypertensives produce exaggerated adrenocortical responses to mental stress

0.50). High heart rate reactors showed significant plasma norepinephrine rises from baseline both to aversive incentives and to reward, although they showed significant cortisol responses only during aversive incentives. In contrast, the low heart rate reactors were unresponsive in cortisol and norepinephrine during either type of incentive. These results support psychoendocrine models which view the norepinephrine response as being nonspecifically related to expenditure of effort regardless of the emotional connotations of the challenge, while cortisol is seen as being secreted primarily during periods of distress. The present data further suggest that cardiovascular reactivity is linked to neuroendocrine reactivity, possibly within the central nervous system.

Effects of caffeine on blood pressure response during exercise in normotensive healthy young men

&NA; Serum cortisol concentrations were compared in 18 borderline hypertensive (BH) and 20 normotensive (NT) men before and after mental stress. Two levels of demand, intermittent reaction time with brief rests and reaction time alternating continuously with mental arithmetic, were used in two consecutive protocols on different days in the laboratory. Continuous, but not intermittent, mental stress produced significant elevations in cortisol levels only in the BH subjects (p < .001). The continuous challenge produced slightly more self‐reported distress in both groups than the intermittent condition, and performance on the mental arithmetic task was more strongly correlated with the cortisol response than was performance on the reaction time task, suggesting that the mental arithmetic task was a key contributor to the cortisol response. Therefore, adrenocortical activity appears sensitive to appropriate stressors in BH subjects. These results indicate the importance of including measures of adrenocortical function in studies of reactivity in subjects at high risk for hypertension.

Effect of behavior state on caffeine's ability to alter blood pressure☆

The possible combined effects of caffeine and exercise on blood pressure (BP) regulation were examined in 34 healthy, normotensive (BP less than 135/85 mm Hg) young men (mean age 27 +/- 3 years) in a placebo-controlled, double-blind crossover design. Each subject performed submaximal and symptom-limited maximal supine bicycle exercise 1 hour apart after ingestion of placebo or caffeine (3.3 mg/kg). Heart rate, BP, cardiac output and peripheral vascular resistance were compared for placebo and caffeine days. Postdrug baseline showed that caffeine increased systolic and diastolic BP and peripheral vascular resistance (p less than 0.001 for each) and decreased heart rate (p less than 0.01) but did not change stroke volume or cardiac output. BP and vascular resistance effects of caffeine remained during submaximal exercise resulting in an additive increase in BP while negative chronotropic effects of caffeine disappeared. At maximal exercise substantially more subjects (15 on caffeine vs 7 on placebo, p less than 0.02) had systolic BP greater than or equal to 230 mm Hg and/or greater than or equal to 100 mm Hg for diastolic BP. Plasma norepinephrine levels were not significantly different across days, but epinephrine was higher at maximal exercise and cortisol was increased post-drug and throughout maximal exercise on caffeine days. Data indicate that caffeine increases BP additively during submaximal exercise and may cause excessive BP responses at maximal exercise for some individuals. The pressor effects of caffeine appear to be due to increasing vascular resistance rather than cardiac output.

Acute Blood Pressure Elevations With Caffeine in Men With Borderline Systemic HyPertension

Caffeine use during exposure to mental stress is an extremely common occurrence. Because both have been shown to alter blood pressure (BP) and its underlying hemodynamic mechanisms, the potential exists for additive or even synergistic effects. Changes in heart rate, BP and noninvasive thoracic impedance measures of left ventricular function were examined in young men (ages 20 to 36) at rest and during a demanding behavioral task performed 40 minutes after predosing with caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) or placebo in a double-blind crossover design. All subjects were healthy young men without history of cardiovascular disease, regular use of nicotine, recreational or prescription drugs or caffeine intolerance. Caffeine abstinence was required for 12 hours before each test session. Systolic and diastolic BP were elevated by both caffeine and the behavioral task alone (p less than 0.01 for each); when combined, caffeines pressor effects were additive to those of the behavioral task. However, caffeines pressor effect was produced by different mechanisms depending on the behavioral state. Caffeine increased systemic vascular resistance (p less than 0.01) under resting conditions, but it enhanced cardiac output (p less than 0.01) during behavioral arousal associated with the task. The combined influence of caffeine and the task increased the number of men in whom peak systolic BP reached hypertensive levels, and also synergistically increased cardiac minute work (p less than 0.01) and the rate-pressure product estimate of myocardial oxygen demand (p less than 0.05). Implications of these findings are discussed for long standing theoretical disputes regarding caffeine, its health consequences, and for methodologic issues in behavioral and clinical studies.

Caffeine enhances the physiological response to occupational stress in medical students.

Whether the vasoconstrictive actions of caffeine are enhanced in hypertensive persons has not been demonstrated. Thus, caffeine (3.3 mg/kg) versus placebo was tested in 48 healthy men (aged 20 to 35 years) selected after screening on 2 separate occasions. Borderline hypertensive men (n = 24) were selected with screening systolic blood pressure (BP) of 140 to 160 mm Hg and/or diastolic BP 90 to 99 mm Hg. Low-risk controls (n = 24) reported no parental history of hypertension and had screening BP < 130/85 mm Hg. Participants were then tested on 2 occasions after 12-hour abstinence from caffeine in each of 2 protocols; this required a total of 4 laboratory visits. Caffeine-induced changes in diastolic BP were 2 to 3 times larger in borderline subjects than in controls (+8.4 vs +3.8 mm Hg, p < 0.0001), and were attributable to larger changes in impedance-derived measures of systemic vascular resistance (+135 vs +45 dynes.s.cm-5, p < 0.004). These findings were consistent and reached significance in both protocols. The percentage of borderline subjects in whom diastolic BP changes exceeded the median control response was 96%. Consequently, whereas all participants exhibited normotensive levels during the resting predrug baseline, 33% of borderline subjects achieved hypertensive BP levels after caffeine ingestion. Thus, in borderline hypertensive men, exaggerated responses to caffeine were: selective for diastolic BP, consistent with greater vasoconstriction, replicated in 2 protocols, and representative of nearly all borderline hypertensives. We suspect that the potential for caffeine to stabilize high resistance states in susceptible persons suggests that its use may facilitate their disease progression, as well as hinder accurate diagnosis and treatment.

Caffeine may potentiate adrenocortical stress responses in hypertension-prone men.

Caffeine (3.3 mg/kg) was tested against a placebo in 20 male medical students during periods of low (no exams) versus high (final exams) work stress. On each of 8 test days, heart rate and blood pressure were measured at baseline and over a 40-min postdrug interval; immediately afterward, blood was drawn to test plasma cortisol and serum lipid concentrations. Exams increased heart rate (p less than .005) and systolic blood pressure (p less than .02). Caffeine decreased heart rate (p less than .0001) and increased systolic blood pressure (p less than .005), diastolic blood pressure (p less than .0001), plasma cortisol levels (p less than .01), and serum cholesterol levels (p less than .02). Caffeine effects were additive with those of exams, and together they increased the number of men showing systolic blood pressures in the borderline hypertensive range. Thus, caffeine use during periods of increased occupational stress may enhance the cumulative stress response.