Caffeine elevates blood pressure response to exercise in mild hypertensive men

AJH 1995; 8:1184--1188

Caffeine Elevates Blood Pressure Response to Exercise in Mild Hypertensive Men Bong Hee Sung, William R. Lovallo, Thomas Whitsett, and Michael F. Wilson

The present study examined the effects of caffeine on blood pressure (BP) mwmlatioa in hypertensive men durin 8 exercise. Twenty mmmdicated, mild hypertensives (HT, BP= 140/90 to 160/105 nun H ~ and 12 a~-matched, nommtensives (NT, BP < 130/ 80 m m IIK) performed 30 rain of mdem~,d bicycle exercise following a sinMJe dose of caffeine (3.3 mK/k ~ equivalent to 2 to 3 cups of coffee) and placebo in a double-blind, croas-over design. Hemodynamic measurements were made at predru$, 40rain postdru8 and durimqj exercise. At predru 8 baseline, FIT had silptiflcantly hisher HR (67 v 57 beats/m/n) and BP (141/96 v 118/72 nun H 8) than NT. At postdru 8 baseline, caffeine increased systolic and diastolic BP, and peripheral vascular resistance (P < .01 in all cases), decreased HR (P < .05) and did not sisnificantly c h e ~ e stroke volume and cardiac output for both ~ o u p s . During exercise, HR response was sreater on caffeine day than placebo day in HT (P < 0.05) only. Systolic

C

affeinated beverages are served frequently on various occasions for an ages. It has been estimated that 80% of Americans above the age of 20 drink caffeinated beverages on a regular basis. 1 Although caffeine affects the central nervous system, cardiovascular activity, From the Department of Medicine, State University of New York (BHS, MFW) and Millard Fillmore Hospitals (BHS, MFW), Buffalo, New York; Departments of Psychiatry and Behavioral Sciences (WRL), and Medicine (TW), University of Oklahoma Health Sciences Center and Veterans Administration Medical Center (WRL), Oklahoma City, Oklahoma. This work was supported by the Oklahoma Center for the Advancement of Science and Technology, and by Grant HL-32050 from the National Heart, Lung, and Blood Institute. Address correspondence and reprint requests to Dr. Bong Hee Sung, Millard Fillmore Hospitals, Department of Cardiology, 3 Gates Circle, Buffalo, NY 14209.

© 1995 by the American Journal of Hypertension, Ltd.

BP was consistently elevated on caffeine day compared to placebo day in both groups (P < .001). Diastolic BP was elevated in HT for 30 min of exercise on caffeine day, but this pressor effect disappeared at 15 rain of exercise in NT. As a result, rate-pressure products were significantly higher on caffeine days in HT at postdrug and during exercise. On caffeine day, 7 (39%) HT and I (8%) NT showed an excessive BP response (>230 for systolic or >120 for diastolic) during exercise. In conclusion, caffeine has significant hemodynamic effects on mild hypertensives at rest and during exercise. The increased rate-pressure products following caffeine during exercise place a greater workload on the heart, and abstinence from caffeine, especially before exercise, may be beneficial for persons with hypertension. Am ] Hypertens 1995;8:1184-1188 KEY WORDS: Caffeine, hypertension, exercise, blood pressure.

and neuroendocrine function, it has become one of the most popular and accepted stimulants. The major cardiovascular effect of caffeine is peripheral vasoconstriction, resulting in elevated blood pressure (BP) with no significant change in cardiac OUtput. 2"4 However, the pressor effects of caffeine have been overlooked because of reported tolerance to hemodynamic effect in habitual users, s Acute tolerance to hemodynamic effects of caffeine does occur in habitual coffee drinkers, however, the pressor response is reinstated after brief abstinence. Numerous studies have reported that caffeine increases BP in habitual consumers after an overnight abstinence. 2-4'6-a We have observed that the pressor response to oral caffeine persisted for 3 h following such abstinence, 6 and others reported that a second cup of coffee of the day induces the pressor effect. 7 0895-7061/95/$9.50 0895-7061(95)00331-2

AJH-DECEMBER 1995-VOL. 8, N O . 12, P A R T 1

Ambulatory BP measured on days of caffeine intake in regular consumers was higher compared to BP taken on placebo days in the work environment, a Therefore, habitual caffeine use does not necessarily lead to complete tolerance. The potential association between coffee consumption and increased risk for cardiovascular disease should not be ruled out on the basis of chronic tolerance. Another attribute of caffeine is that it not only raises BP at rest 2-4 but also potentiates the pressor r e s p o n s e seen d u r i n g occupational a n d mental stress. 6"9 We have also reported that caffeine and exercise additively increase BP in normotensive men 3 and causes excessive BP responses at maximal exercise in hypertension-prone individuals a'4. Although pressor effects of caffeine have also been demonstrated in hypertensive individuals 6'1° at rest, possible interaction between stress and caffeine consumption in this population is not well studied. Because of unregulated wide usage of caffeine, health consequences are of great concern for health care providers as well as general public. Therefore, careful experiments to determine the effect of caffeine on cardiovascular health are warranted. Caffeinated beverages are frequently consumed prior to and during recreational and competitive exercise, yet, the influence of caffeine on BP responses during exercise in hypertensive populations is currently unknown. The present study examined the effects of caffeine on heart rate and BP response in hypertensive men at rest and during exercise. This information will be of value in determining whether or not caffeine use may adversely influence BP at such times in hypertensive men and if reduction in its use plays a role in the management of hypertension. METHODS Subjects Thirty-two healthy men from the community (ages 30 to 45), including 12 normotensives and 20 hypertensives, were studied. All had normal cardiovascular function determined by a normal medical history, physical examination and electrocardiogram (ECG). The study groups were defined as normotensive (NT), BP < 130/80 m m Hg with a negative parental history of hypertension, and mild hypertensives (HT) if BP = 140/90 to 160/105 mm Hg by sitting BP readings measured using an automated Critikon/ Dynamap oscillometric monitor. Seven HT were on no medications and 13 HT were on either angiotensin converting e n z y m e inhibitors (seven subjects), 13-blockers (four subjects) and hydrochlorothiazide (HCTZ) (two subjects). All antihypertensive medications were tapered accordingly prior to the BP screening. There were 2 to 4 weeks interval between the BP screening to exercise sessions. The subject characteristics of the study groups are summarized in Table 1.

CAFFEINE AND EXERCISE IN HYPERTENSIVES 1185

TABLE 1. SUBJECT CHARACTERISTICS A N D PREDRUG BASELINE HEMODYNAMIC VALUES BETWEEN NORMOTENSIVE A N D HYPERTENSIVE GROUPS Normotensive

Hypertensive

(n = 12)

(n = 18)

Variable Age (years) Height (cm) Weight (kg) Body surface area (m2) Quetelet index

38 184 83 2.06

--- 5 + 7 4- 14 +- 0.2

39 180 93 2.14

P

--- 5 + 6 +- 13 + 0.2

NS NS .07 NS

2.4 + 0.3

2.9 + 0.4

.01

151 + 82

232 + 220

NS

56 +- 9

67 --- 9

.001

117 -+ 5

138 + 13

.001

71 -+ 7

94 + 12

.001

6.2 + 0.7

6.5 + 0.5

NS

106 - 10

99 +-- 7

NS

1128 - 140

1430 + 299

.05

(g/cm2) Caffeine consumption (mg/day) Heart rate (beats/min) Systolic BP (mm Hg) Diastolic BP (ram Hg) Cardiac output (L/rain) Stroke volume (mL) Peripheral vascular resistance (dynes. sec • cm-

5)

Values are mean + SD.

Inclusion criteria were: weight within 30% of normal, according to Metropolitan Life Insurance Company norms, less than one pack/day cigarette smoking, less than two alcoholic beverages/day, and no medication during the study. Subjects were abstinent from caffeine, ethanol, and nicotine for >- 12 h prior to each session. Usual caffeine consumption by the study participants was equivalent to 1 to 8 cups of coffee per day with no reported caffeine intolerance or side effects. Study D e s i s n Each subject was tested in a doubleblind, crossover design on placebo and caffeine days. Test sessions were scheduled at least 2 days apart at 8:00 AM after 12 h abstinence from caffeine. Each session consisted of the following: instrumentation of the subject with automated BP cuff and electrodes for impedance cardiography, 20 min supine rest, predrug measurements (2 min), caffeine or placebo drink and drug absorption period (40 min), postdrug measurements (2 min), pre-exercise baseline measurements (2 min), extended bicycle exercise (30 min), recovery period 10 min. The full protocol required approximately 2 h.

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SUNG ET AL

Exercise Protocol

Each subject performed supine bicycle exercise at 200 kg-m/min (kpm) (3 min), 400 kpm (3 min), and 600 kpm (3 rain) as a warm-up period, followed by 21 min continuous exercise at 400 kpm. Criteria for early termination of exercise were: symptoms of extreme fatigue or shortness of breath, or BP exceeding 230 m m Hg for systolic or 120 m m Hg for diastolic during exercise. Drug Administration Caffeine (3.3 mg/kg caffeine anhydrous; Amend Drug and Chemical Co, Irvington, NJ) mixed with 6 oz unsweetened grapefruit juice or the grapefruit juice alone as placebo, was administered orally. Heart rate and ECG were recorded for 1-min intervals and BP was measured by an automated BP monitor (Paramed). Rate pressure product (RPP = HR x SBP, an index of myocardial 0 2 demand) was calculated. Stroke volume and cardiac output were measured by impedance cardiogr_a~.~.y.ll Peripheral vascular resistance (dyne-sec.cm-) was computed by dividing the mean BP by the cardiac output and multiplying by a conversion factor of 80. All cardiovascular measurements were made at predrug, postdrug, pre-exercise baseline, during a warm-up period and min 15, 20, 25, and 30 of extended exercise, and at recovery. Two readings were obtained for each period. Saliva samples were collected for determination of caffeine concentrations at predrug, postdrug baseline, and the end of exercise. Measurements

Bioassay Saliva caffeine concentrations were measured by high-pressure liquid chromatography. 12 Statistical Analysis Hemodynamic changes were analyzed using a two groups (HT v NT) x two drugs (caffeine v placebo) × six periods (baseline, warm-up, 15, 20, 25, and 30 rain) analysis of variance with repeated measures using Systat (Systat Inc, Evanston, IL). Statistical significance was set at the level of P < .05. RESULTS

Two hypertensive patients were discharged from the study because their casual resting BP were greater than 160/105 m m Hg during the study. (They had previously been on [~blockers.) The "final study group consisted of 12 NT and 18 liT. There were no differences in age, height, body surface area, or daily caffeine consumption. The HT group was heavier (93 v 83 kg, P < .07) and had a significantly higher Quete* let index than the NT group (P < .01). Saliva caffeine levels were measm'ed to verify caffeine and placebo administration and compliance with the required abstinence from dietary caffeine prior to study. Values for all placebo samples and at predrug on caffeine days ranged from 0.0 to 0.1 p,g/

mL, confirming compliance and adherence to the dosing schedule. Mean ( - SD) saliva caffeine concentrations of both groups were 4.95 -+ 1.2 t~g/mL at 40-min postdrug and 4.1 --. 0.9 ~g/mL at the end of exercise, and there was no significant difference between groups. Preliminary analyses revealed no difference in predrug hemodynamic values on either days. Therefore these data were averaged to represent the predrug period. As expected the HT group had significantly higher BP (141/96 v 118/72 m m Hg) than NT at predrag baseline. The HT group also had significantly higher baseline HR (67 v 57 beats/min), rate-pressure product (94 x 102 v 67 x 102) and peripheral vascular resistanoe (1430 v 1128 dyne.s.cm-S). The NT and HT groups had similar baseline stroke volumes (106 v 99 mL) and cardiac outputs (6.2 v 6.5 L/min). Comparison of 40 min postdrug with predrug baseline readings showed that, for both groups, caffeine increased systolic and diastolic BP, and peripheral vascular resistance (P < .01 in all cases) and decreased heart rate (P < .05). Caffeine did not significantly change resting stroke volume or cardiac output. There were no significant group differences in resting hemodynamic effects of caffeine. Submaximal extended exercise was selected for the study to prevent excessive BP responses to vigorous exercise in subjects with hypertension and because it represents a common pattern of exercise among the general population. Eleven of 12 NT subjects completed 30 min exercise and none showed a hypertensive BP response on the placebo day. On the caffeine day, exercise was terminated at 25 min for one NT subject (8%) because his BP was 238/82 m m Hg. Another hiT subject could not complete the 30-min exercise on either day due to leg pain. Four HT subjects (4/18, 22%) showed BP response >230 m m Hg for systolic or > 120 m m Hg for diastolic BP during exercise on placebo day, and 7 HT subjects (7/18, 39%) had ~ v e BP response on the caffeine day. HR response to exercise was similar on both days for the NT group but the HR response was significantly greater on the caffeine day for the HT group (P < .05). Systolic BP was significantly higher on the caffeine day for both groups (P < .001). Increased diastolic BP to caffeine was maintained for the entire 30 min in the HT group, compared to 15 min in the NT group. Systolic BP was consistently elevated on caffeine day, compared to placebo day in both groups (P < .001). Although increment of BP by caffeine was greater in HT than NT (11 m m Hg v 6 m m Hg) during exercise, it was not statistically significant. Diastolic BP was elevated in HT for 30 min of exercise on caffeine day, but this pressor effect disappeared at 15 min of exercise in NT. There was significant drug by group interaction (P < .05).

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To examine possible carryover effects from the withdrawal of antihypertensive medication on hemodynamic response to caffeine and exercise, we divided the HT group into three groups (seven on no medication, seven on ACE inhibitors, four on either 13-blockers or diuretics). There was no significant difference on HR and BP responses to caffeine and exercise between the groups. Given the increase in HR and BP, rate-pressure product by caffeine during exercise was significantly greater on caffeine day compared to placebo day and there was a significant group by drug interaction (F = 6.54, P < .01) due to both increase in heart rate and systolic BP in HT group. Rate-pressure product indicates myocardial oxygen demand, 13 and this increased rate-pressure product placed greater workload on the cardiovascular system of HT group. Ratepressure product response to extended bicycle exercise was compared between NT v HT on caffeine and placebo days (Figure 1). DISCUSSION The present study demonstrates that caffeine raises BP and alters hemodynamics in NT and HT men at rest and during exercise. In agreement with earlier work, 3'4 systolic BP was higher in both groups at rest and throughout the period of exercise on caffeine day. Diastolic BP was elevated in HT for 30 min of exercise on caffeine day, but this pressor effect disappeared at 15 min of exercise in the NT group, suggesting that the NT group was able to override the pressor effect of caffeine during extended exercise. In contrast to NT, the HT appears to have a reduced ability override the vascular effects of caffeine during Rate-Pressure

exercise. The two groups also differed regarding the effect of caffeine on HR during exercise, with hypertensives showing a higher mean HR following caffeine. Their greater HR response after caffeine along with their elevated blood pressures resulted in a significantly higher rate-pressure product. Ratepressure product is an index of oxygen demand by the heart, 13 and the higher rate-pressure product among hypertensives suggests that caffeine use prior to exercise may unnecessarily raise the workload of the heart in this group. The cardiac complications of hypertension include left ventricular hypertrophy and greater risk of coronary heart disease. Both conditions are aggravated by elevated cardiac workloads. Therefore both the BP and rate-pressure product responses to exercise after caffeine intake indicate undesirable effects among patients with hypertension. In this study, all hypertensive patients were off of their medication for 2 to 4 weeks. It is unknown whether the pressor effect of caffeine during exercise would be modified by antihypertensive therapy and particularly whether different types of medication have a differential response. Freestone and Ramsey examined patients with mild hypertension following caffeine ingestion and found that coffee (200 mg caffeine) significantly increased resting blood pressure by 10/7 mm Hg for 1 to 2 h post-ingestion. ~4 This pattern was also seen in patients being treated with thiazide diuretics. The effect of caffeine on BP does not appear to be altered by selective and nonselective I~-blockade.15 Although there is a paucity of data concerning the effects of caffeine during treatment with antihypertensive agents, these studies suggest that anti_hypertensive medication may not protect against the pressor effect of caffeine.

Product

rate-pressure product response to exercise was compared between normotensives versus hypertensives on caffeine and placebo days. Measurements were obtained at predrug baseline (PreD), 40-min postdrug (PostD), baseline before exercise (BL), 9-min warm-up period, 15, 20, 25, and 30 min of exercise at workload of 400 kpm and 5 rain postexercise (PostEx). There was a stepwise increase in ratepressure product from normotensives on placebo day (NT-P), normotensives on caffeine day (NT-C), hypertensives on placebo day (HTP), and hypertensives on caffeine day (HT-C). FIGURE 1.

x 10 300 250 200 150 100 50 PreD PoetD

BL Warmup

16

20

26

30

PoatEx

TIME (MINUTES)

NT-P

INT-C

~HT-P

/HT-C

1188 SUNGET AL

AJH-DECEMBER 1995-VOL. 8, NO. 12, PART 1

Caffeinated beverages are frequently consumed prior to and during exercise. Increased HR and BP thus, rate-pressure product by caffeine during exercise places a greater workload on the heart of hypertensive individuals, which may add to the chronic pressure overload leading to a further deterioration due to the hypertensive process. Although more evidence is required, reduction in caffeine consumption may have a role to play in the marm@ement of hypertension. Abstinence from caffeine especially before exercise may be beneficial, especially in certain targeted groups such as those with hypertension.

10.

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