Bong Hee Sung

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.

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.

Vasodilatory Effects of Troglitazone Improve Blood Pressure at Rest and During Mental Stress in Type 2 Diabetes Mellitus

The present study examined the hemodynamic mechanisms of blood pressure (BP) lowering by troglitazone in patients with type 2 diabetes mellitus (DM) at rest and during a mental arithmetic test (MAT). Twenty-two patients with DM with normal to high-normal BP and 12 controls matched for age, gender, glucose tolerance, and BP were studied. DM subjects showed significantly higher systolic BP response during MAT than controls (157 versus 139 mm Hg; P<0.01). All 22 DM patients and 5 of 12 controls had systolic BP >140 mm Hg during MAT. Heart rate and diastolic BP were not significantly different between the 2 groups. The DM group was then randomized to receive troglitazone (n=10; 400 mg/d) or glyburide (n=12; 20 mg/d). MAT was repeated after 6 months of treatment. Both treatments reduced glucose equally (-1.7 mmol/L for troglitazone and -1.5 mmol/L for glyburide), but only troglitazone reduced insulin (-15 microU/mL; P<0.001) and C-peptide (-0.9 ng/mL; P<0.02) levels. Troglitazone significantly reduced BP at baseline (P<0.05) and systolic BP response to MAT (P<0.01), whereas glyburide did not affect BP at baseline or during MAT. Stroke volume and cardiac output did not change with either drug, but troglitazone decreased peripheral vascular resistance (-112 dyne. s. cm(-5); P<0.05). Improved insulin resistance rather than an improved glycemic control is associated with lower resting and stress BP values in patients with DM. A reduction in vascular resistance may be a primary hemodynamic mechanism of the manner in which troglitazone lowers BP. Insulin sensitizers may offer potential therapeutic advantage in subjects with DM with elevated BP.

Blood Pressure Response to Caffeine Shows Incomplete Tolerance After Short-Term Regular Consumption

Abstract—Caffeine acutely raises blood pressure (BP). The clinical significance of this effect depends on whether BP responses persist in persons who consume caffeine on a daily basis. Accordingly, the ability of caffeine to raise BP after 5 days of regular daily intake was tested in a randomized controlled trial. Individual differences in tolerance formation were then examined. Men (n=49) and women (n=48) completed a double-blind, crossover trial conducted over 4 weeks. During each week, subjects abstained for 5 days from dietary caffeine and instead used capsules totaling 0 mg, 300 mg, and 600 mg of caffeine per day in 3 divided doses. On day 6, in the laboratory, they used capsules with either 0 mg or 250 mg of caffeine at 9:00 am and 1:00 pm. Systolic/diastolic BP increases as a result of 250 mg of caffeine remained significant (P <0.006/0.001) at all levels of previous daily consumption. Individual difference comparisons found that although half the subjects had complete loss of systolic and diastolic BP responses to the challenge doses, the other half showed no loss in BP response, even after using 600 mg of caffeine per day for the previous 5 days (F >7.90, P <0.001). The sexes did not differ in degree of tolerance formation. Daily caffeine consumption failed to eliminate the BP response to repeated challenge doses of caffeine in half of the healthy adults who were tested. Caffeine may therefore cause persistent BP effects in persons who are regular consumers, even when daily intake is at moderately high levels.

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

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.

Insulin Attenuates Norepinephrine- Induced Venoconstriction: An Ultrasonographic Study

To directly assess insulin-related venomotor changes objectively and quantitatively, we used a modified ultrasonographic technique to measure venous diameter. Ten healthy men and women were studied by use of an Acuson 128 XP ultrasonograph with a linear 7.5-MHz ultrasonographic transducer (sensitivity, +/- 0.1 mm). Venous diameter was measured with the arm kept at 30 degrees elevation and with a pneumatic cuff above the elbow inflated at 40 mm Hg for the last 2 minutes of each 5-minute observation period. Norepinephrine was infused at incremental concentrations of 12.5, 25, 50, and 100 ng/min (75, 150, 300, and 600 pmol/min, respectively) for 5 minutes each. Maximal venoconstriction was achieved by the dose of 100 ng/min norepinephrine, which was then combined with insulin doses of 8, 16, 24, and 32 microU/min (60, 120, 180, and 230 fmol/min, respectively) for 5 minutes each. In six different subjects, methylene blue, an inhibitor of guanylate cyclase, was infused simultaneously with 32 microU/min insulin and 100 ng/min norepinephrine. Mean resting diameter of the vein (1.8 +/- 0.6 mm [mean +/- SD]) increased (to 3.0 +/- 1.0 mm) after cuff inflation. Incremental doses of norepinephrine caused highly reproducible dose-dependent decrease in venous diameter (to 1.8 +/- 0.6 mm, P < .001). Incremental doses of insulin, when combined with the maximum dose of norepinephrine, caused highly reproducible dose-dependent increases in mean venous diameter (P < .001) compared with norepinephrine alone. Methylene blue, which had no independent effect on venous diameter, inhibited the venodilator effect of insulin (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels

Objective: Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake. Methods: Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM. Results: After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period. Conclusion: Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis. ANOVA = analysis of variance; C = caffeine; HPAC = hypothalamic-pituitary-adrenocortical axis; P = placebo; ACTH = adrenocorticotropin.

Effects of Cholesterol Reduction on BP Response to Mental Stress in Patients With High Cholesterol

Impaired endothelium-dependent vascular relaxation has been reported in patients with high cholesterol (HC), but the systemic effects of elevated cholesterol on blood pressure (BP) and BP reactivity to stress have not been studied. We examined the BP response to a standard mental arithmetic test (MAT) in 37 healthy, normotensive HC subjects and 33 normal cholesterol controls (NC). Both groups had similar age, body mass index, and gender distribution. HC had slightly higher systolic BP at baseline (122 v 118 mm Hg, P < .05) than NC and systolic BP response during MAT was significantly higher in HC compared to NC (18 +/- 8 v 10 +/- 5 mm Hg, P < .05). Maximal changes in systolic BP were significantly correlated with cholesterol (R = 0.41, P < .001), whereas heart rate and diastolic BP changes were unrelated to serum cholesterol. To confirm that BP reactivity was dependent on cholesterol, MAT was repeated after treatment with 20 mg/day of lovastatin, a hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, for 6 weeks using a cross-over design in 26 HC subjects. Lovastatin significantly altered lipid profiles (-26% total cholesterol, +8% HDL, -34% LDL). A small decrease in systolic BP at baseline (-3 mm Hg, P = NS) and significantly lower systolic BP (-8 mm Hg, P < .05) during MAT was observed after the treatment with lovastatin. In conclusion, patients with high cholesterol had an exaggerated systolic BP response to MAT. Decreased BP reactivity during HMG-CoA reductase inhibitor therapy suggests that lowering cholesterol may have a role in the overall control of BP.

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

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.

The effect of caffeine on blood cortisol levels and blood pressures was examined during rest and in response to a challenging psychomotor task in men with a low versus high risk of essential hypertension. Thirty-four healthy men ages 21–35 years were selected such that 17 were at high risk for hypertension (positive parental history and screening blood pressures of 135/85–155/95 mm Hg) and 17 were at low risk (negative parental history and no pressures above 132/84 mm Hg). Testing consisted of quiet rest (20 minutes); oral placebo (grapefruit juice) or caffeine administration (3.3 mg/kg in grapefruit juice); rest during a postdrug absorption period (40 minutes); work on an unsignalled simple reaction time task (15 minutes); and quiet rest (20 minutes). Blood pressures were recorded at 2-minute intervals, and blood samples were withdrawn via an indwelling catheter at the end of the baseline, drug absorption, task, and recovery periods. The combination of task plus caffeine produced the highest blood pressures in men at risk for hypertension. Cortisol levels were found to be sustained during rest in members of the high risk group after they had consumed caffeine, whereas members of the low risk group showed a modest decline. The high risk subjects also showed a significant rise in cortisol during (+3.7 μg/dl) and after (+4.0 μg/dl) work on the reaction time task after caffeine consumption. In the low risk group, cortisol responses to caffeine were smaller (+2.2 μg/dl or less) when compared with responses to the task after caffeine consumption. The results suggest that these men at high risk for hypertension were sensitive to caffeine and that caffeine combined with a demanding psychomotor challenge produced neuroendocrine signs of stress. These findings point toward the need for studies of the role of caffeine in modifying stress responses of targeted groups such as those at risk for hypertension.