BACKGROUND

Heart rate recovery (HRR) has been shown to predict cardiovascular disease mortality. HRR is delayed in hypertension, but its association with prehypertension (PHT) has not been well studied.

METHODS

The study population consisted of 683 asymptomatic individuals (90% men, aged 47±7.9 years). HRR was defined as peak heart rate minus heart rate after a 2-minute rest. PHT was categorized into stage I (systolic blood pressure (SBP) 120–129mm Hg or diastolic BP (DBP) 80–84mm Hg) or stage II (SBP 130–139mm Hg or DBP 85–89mm Hg). Logistic regression was used to generate odds ratios (ORs) for the relationship between HRR and PHT.

RESULTS

The mean HRR was lower in the PHT groups than in those who were normotensive (60 bpm and 58 bpm in stages I and II PHT vs. 65 bpm in normal BP; P <0.01). Persons with PHT were more likely to be in the lowest quartile of HRR compared with those with normal BP (adjusted OR, 3.80 and 95% confidence interval [CI], 1.06, 13.56 for stage II PHT and adjusted OR, 3.01 and 95% CI 1.05, 8.66 for stage I PHT). In a fully adjusted model, HRR was still significantly associated with both stages of PHT.

CONCLUSION

Among asymptomatic patients undergoing stress testing, delayed HRR was independently associated with early and late stages of PHT. Further studies are needed to determine the usefulness of measuring HRR in the prevention and management of hypertension.

Prehypertension (PHT), defined as systolic blood pressure (SBP) between 120 and 139mm Hg or diastolic blood pressure (DBP) between 80 and 89mm Hg, in individuals who are untreated1 is known to predict future development of hypertension and is associated with increased risk of developing a cardiovascular event.2–4 In the United States, the prevalence of PHT among adults aged >20 years is about 27%,5 and the 4-year risk of progression from PHT to hypertension is between 17.6% in those with early PHT (SBP 120–129mm Hg or DBP 80–84mm Hg) and 37.3% in those with late PHT (SBP 130–139mm Hg or DBP 85–89mm Hg).6 PHT has been associated with several markers of cardiovascular risk including microalbuminuria,5 elevated uric acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose, and reduced high-density lipoprotein cholesterol (HDL-C).7–10

Findings from the Framingham Heart Study suggest that autonomic dysfunction, as measured by heart rate variability, might be implicated in the development of hypertension.11 However, the pathogenetic mechanisms underlying PHT development remain unclear. Recently, associations between autonomic dysfunction and PHT have been made.12–15 These include overactivity of the sympathetic nervous system and cardiac parasympathetic dysfunction. Heart rate recovery (HRR) after exercise is a useful marker of cardiac parasympathetic function.16 It is measured as the difference between the peak heart rate during exercise and the heart rate at an interval after the end of the exercise, usually 30 seconds or 1, 2, or 4 minutes. Delay in HRR after exercise has repeatedly been shown to be associated with all-cause cardiovascular mortality.17–22 However, studies examining the association between HRR after exercise and PHT are scant. The only study we found showed that the prevalence of delayed HRR (<18 bpm in the first minute) was about 2 times that in prehypertensive patients compared with a control group with optimal BP.23

Here, we examine the association between HRR and severity of PHT. It was our hypotheses that as BP increases, the likelihood of having delayed HRR increases.

METHODS

This cross-sectional study was conducted in a population of 683 asymptomatic individuals free of known cardiovascular disease. These individuals were executives at several private companies and underwent exercise stress testing as part of an obligatory health evaluation paid for by their employers. The participants included in the study had no self-reported history of a cardiovascular event, were asymptomatic and devoid of physical findings suggestive of cardiovascular disease, and did not have electrocardiogram findings suggestive of coronary disease. The study was conducted at the Preventive Medical Center of the Hospital Israelita Albert Einstein, Sao Paulo, Brazil, between July 1999 and June 2003 and was approved by the institution’s review board.

Details of the methods have been described elsewhere.24 In brief, patients received exercise testing according to the Bruce protocol. Prior to commencing exercise, participants had their sitting and standing BPs taken with calibrated aneroid devices. Prior to commencing the exercise testing, 3 resting BPs were taken, the first being after 5 or more minutes of rest, all on the same day in the sitting position using the method proposed by the American Heart Association.25 The average of the 3 BPs was used as the baseline BP for this analysis. Appropriate-sized cuffs based on arm circumference were used. A single BP measurement was also obtained immediately before commencing exercise while the participant was standing on the treadmill. Single BP measurements were obtained at exercise peak; at the end of the stress testing stages; and at 2, 4, and 6 minutes post-exercise testing using the same instruments. Weight (in kilograms) and height (in meters) were measured using a standard physician’s weight scale and a stadiometer. Body mass index (BMI) was calculated as body weight (kg) divided by the square of height (m). Percent body fat was measured by bioimpedance (Tanita Corp., Japan). Fasting samples were obtained for total cholesterol, HDL-C, and triglycerides. LDL-C was calculated by the Friedwald formula. A pertinent, self-reported clinical history, including current smoking, diabetes mellitus, hypertension, and medication use, was taken from each participant. Presence of cigarette smoking (referred to here as “smoking”) was only considered in those who smoked at least 1 cigarette in the month preceding the examination.

All participants underwent exercise stress testing according the Bruce protocol.26 Metabolic equivalents (METs) were determined from the peak oxygen consumption at the last stage of exercise such that 1 MET = 3.5mL O2/kg mL. Baseline heart rate, peak heart rate during exercise, and heart rate at 2 and 4 minutes immediately after exercise were measured. Baseline BP, peak BP during exercise, and BP at 2 and 4 minutes after exercise were also measured. For this analysis, HRR was defined as peak heart rate minus heart rate at 2 minutes after exercise. HRR was categorized according to quartiles—Q1 to Q4—with Q1 being the slowest rate of HRR and Q4 being the fastest.

In the categorization of blood groups, a combination of resting BP measurements, use of antihypertensive medications, and a self-reported history of hypertension were used. A history of hypertension was defined as reporting a diagnosis of hypertension at the time of presentation or reporting use of antihypertensive medication. Optimal BP was defined as SBP/DBP <120/80mm Hg, not on treatment for hypertension, and with no known history of hypertension. PHT was categorized into 2 groups. Stage 1, or early PHT, was defined as resting (sitting) SBP 120–129mm Hg or DBP between 80 and 84mm Hg in persons not on antihypertensive medication. Stage 2, or late PHT, was defined as SBP between 130 and 139mm Hg or DBP 85–89mm Hg in those not on antihypertensive medication. Persons with blood SBP ≥140mm Hg or DBP ≥90mm Hg were categorized as hypertensive. Similarly, those on treatment for hypertension or those with a history of hypertension regardless of measured BP were categorized as hypertensive. BP recovery was defined as 2-minute and 4-minute BP decline from the peak BP.

Statistical analysis

Continuous variables were graphically examined for normality. Continuous variables are presented as mean ± standard deviation or median (interquartile range); categorical variables are presented as number (percent). Analysis of variance was used to determine significance in differences across the means of continuous variables including HRR. The Bonferroni test of multiple comparisons was used to compare normally distributed continuous variables within BP groups. The Kruskal–Wallis test was used to compare nonnormally distributed continuous variables. The χ2 test of independence was used to compare frequencies across categorical variables. Pearson and Spearman tests of correlation were conducted to determine the association between BP changes during the exercise stress test and HRR at 2 minutes, both expressed as continuous variables. We divided HRR into quartiles. To test for the association between BP groupings and quartiles of HRR, we used logistic regression adjusting for age, smoking, and BMI in the first model and adjusting for age, smoking, BMI, diabetes mellitus, exercise capacity (METs), SBP recovery at 2 minutes, and SBP recovery at 4 minutes in the second model. Odds ratios (ORs) with 95% confidence intervals (CIs) were generated for the association between stages of hypertension and HRR using optimal BP and the highest quartile of HRR as references. All analyses were performed using Stata statistical software, version 12.0 (StataCorp, College Station, TX). A P value <0.05 was considered statistically significant.

RESULTS

A total of 683 participants who had complete data were included in this study. Approximately 90% of participants were male, with a mean age of 47±8 years. The prevalence of PHT was high (about 53%) as was the prevalence of smoking (50%). The mean 10-year Framingham risk (percent) was 9.3±8.0. Details of the baseline characteristics can be found in Table 1.

Table 1.

Baseline characteristics of participants according to blood pressure category

Characteristic Optimal blood pressure Stage 1 Prehypertensiona Stage 2 Prehypertensionb Hypertensionc All participants 
Number of patients (%) 60 (8.8) 272 (39.8) 93 (13.6) 258 (37.8) 683 (100.0) 
Male sex (%) 41 (68.3) 238 (87.5) 91 (97.9) 246 (95.4) 616 (90.2)* 
Smoker (%) 26 (43.3) 134 (49.3) 44 (47.3) 139 (53.9) 343 (50.2) 
Diabetes (%) 0 (0.0) 5 (1.8) 2 (2.2) 11 (4.3) 18 (2.6) 
On antihypertensive medication (%) None None None 101 (39.2) 101 (14.79) 
Mean age (years) 44.7±7.4 44.8±7.1 47.5±7.2 50.0±7.9 47.1±7.8* 
Mean total cholesterol (mg/dL) 200±40 201±39 205±34 214±43 207±40* 
Mean low-density lipoprotein cholesterol (mg/dL) 122±35 127±37 129±28 131±35 128±35 
Mean high-density lipoprotein cholesterol (mg/dL) 52±15 47±13 44±11 44±14 46±13* 
Mean triglycerides (mg/dL) 117±68 146±105 162±99 189±138 162±118* 
Mean 10-year Framingham risk (%) 5.7±5.9 6.8±6.4 10.1±8.0 12.6±8.6 9.3±8.0* 
Mean body mass index (kg/m224.9±2.3 26.3±3.8 27.6±4.4 28.5±3.8 27.1±4.0* 
Mean % body fat 26.7±5.1 27.6±6.7 28.2±5.1 29.3±4.6 28.2±5.7* 
Characteristic Optimal blood pressure Stage 1 Prehypertensiona Stage 2 Prehypertensionb Hypertensionc All participants 
Number of patients (%) 60 (8.8) 272 (39.8) 93 (13.6) 258 (37.8) 683 (100.0) 
Male sex (%) 41 (68.3) 238 (87.5) 91 (97.9) 246 (95.4) 616 (90.2)* 
Smoker (%) 26 (43.3) 134 (49.3) 44 (47.3) 139 (53.9) 343 (50.2) 
Diabetes (%) 0 (0.0) 5 (1.8) 2 (2.2) 11 (4.3) 18 (2.6) 
On antihypertensive medication (%) None None None 101 (39.2) 101 (14.79) 
Mean age (years) 44.7±7.4 44.8±7.1 47.5±7.2 50.0±7.9 47.1±7.8* 
Mean total cholesterol (mg/dL) 200±40 201±39 205±34 214±43 207±40* 
Mean low-density lipoprotein cholesterol (mg/dL) 122±35 127±37 129±28 131±35 128±35 
Mean high-density lipoprotein cholesterol (mg/dL) 52±15 47±13 44±11 44±14 46±13* 
Mean triglycerides (mg/dL) 117±68 146±105 162±99 189±138 162±118* 
Mean 10-year Framingham risk (%) 5.7±5.9 6.8±6.4 10.1±8.0 12.6±8.6 9.3±8.0* 
Mean body mass index (kg/m224.9±2.3 26.3±3.8 27.6±4.4 28.5±3.8 27.1±4.0* 
Mean % body fat 26.7±5.1 27.6±6.7 28.2±5.1 29.3±4.6 28.2±5.7* 

Abbreviations: DBP, diastolic blood pressure; HR, heart rate; HRR, heart rate recovery; SBP, systolic blood pressure.

aSBP 120–129mm Hg or DBP 80–84mm Hg.

bSBP 130mm Hg–140mmHg or DBP 85–89mm Hg.

cSBP ≥140mm Hg or DBP ≥90mm Hg.

*Statistically significant (P ≤ 0.05) across hypertensive groups.

There was a reduction in baseline heart rate with increasing quartiles of HRR such that those in the fastest HRR quartile (Q4) had the slowest mean heart rate at baseline and those in the slowest quartile (Q1) had the fastest baseline heart rate on average (P < 0.001). By contrast, the peak heart rate increased with increasing rates of HRR (P < 0.001). Baseline SBP and DBP and peak DBP also showed a decline in the mean with increasing HRR quartiles (P < 0.001). However, there was no difference in the peak SBP across quartiles of HRR. Table 2 details these findings.

Table 2.

Heart rate and blood pressure characteristics grouped by quartiles of heart rate recovery

Characteristic Q1 Q2 Q3 Q4 P value 
Mean baseline heart rate (± SD) 75.6±10.8 75.0±10.9 73.1±11.2 69.3±10.8 <0.001 
Mean peak heart rate (± SD) 150.7±16.7 164.2±11.6 167.7±10.2 171.7±11.5 <0.001 
Baseline SBP (± SD) 132±16 126±14 126±14 122±13 <0.001 
Peak SBP (± SD) 181±27 180±25 176±25 176±26 0.24 
Baseline DBP (± SD) 84±9 82±8 82±7 80±8 <0.001 
Peak DBP (± SD) 83±14 80±14 79±12 77±10 <0.001 
Exaggerated BP response (%) 16.8 13.6 10.8 12.2 0.479 
Characteristic Q1 Q2 Q3 Q4 P value 
Mean baseline heart rate (± SD) 75.6±10.8 75.0±10.9 73.1±11.2 69.3±10.8 <0.001 
Mean peak heart rate (± SD) 150.7±16.7 164.2±11.6 167.7±10.2 171.7±11.5 <0.001 
Baseline SBP (± SD) 132±16 126±14 126±14 122±13 <0.001 
Peak SBP (± SD) 181±27 180±25 176±25 176±26 0.24 
Baseline DBP (± SD) 84±9 82±8 82±7 80±8 <0.001 
Peak DBP (± SD) 83±14 80±14 79±12 77±10 <0.001 
Exaggerated BP response (%) 16.8 13.6 10.8 12.2 0.479 

Q1, heart rate recovery (HRR) at 2 minutes in the first (slowest) quartile; Q2, HRR in the second quartile; Q3, HRR in the third quartile; Q4, HRR in the fourth (fastest) quartile. Baseline SBP and DBP are resting BP measured prior to commencing the stress test. Exaggerated BP response is peak exercise SBP ≥210mm Hg.

Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure; SD, standard deviation.

Heart rate analysis showed that there was an increase in the baseline heart rate (P <0.002) and a reduction in peak heart rate (P < 0.001) with increasing BP. There was progressive reduction in HRR at 2 minutes from optimal BP through the early (stage 1) and late (stage 2) stages of PHT to hypertension. Compared with those with optimal BP, the HRR at 2 minutes was slower in those with hypertension (P < 0.001) and in those with late PHT (stage 2; P = 0.019) but not stage 1 PHT (P = 0.19). Compared with those with optimal BP, the peak heart rate was significantly reduced in those with hypertension (P = 0.002) but not in the prehypertensive groups (P = 0.54 for stage 2 PHT and P =1.00 for stage 1 PHT). Other details can be found in Table 3. Figure 1 shows increasing frequencies of persons with HRR in the first quartile (lowest) and decreasing frequencies of those in the fourth quartile (highest) as BP increases from optimal through PHT to hypertension.

Table 3.

Heart rate characteristics according to blood pressure category

Characteristic Optimal blood pressure Stage 1 Prehypertensiona Stage 2 Prehypertensionb Hypertensionc P value 
Baseline (supine) heart rate 72.2±11.4 71.9±11.1 73.0±10.1 76.6±11.6 <0.001 
% with HRR ≤ population median (58 bpm) 38.3 44.1 57.0 63.1 <0.001 
Mean HRR at 2 minutes (bpm) 65.0±12.5 60.4±13.2 57.7±20.7 54.0±14.4 <0.001 
Mean peak heart rate (standard deviation; bpm) 167.5±10.3 165.7±13.7 163.3±16.8 159.8±16.1 <0.001 
Mean HRR/peak heart rate % 38.8±6.9 36.4±8.0 34.5±12.6 33.5±8.1 <0.001 
Positive stress test (%) d 15 (26.3) 65 (25.2) 24 (14.6) 61 (37.0) 0.989 
Characteristic Optimal blood pressure Stage 1 Prehypertensiona Stage 2 Prehypertensionb Hypertensionc P value 
Baseline (supine) heart rate 72.2±11.4 71.9±11.1 73.0±10.1 76.6±11.6 <0.001 
% with HRR ≤ population median (58 bpm) 38.3 44.1 57.0 63.1 <0.001 
Mean HRR at 2 minutes (bpm) 65.0±12.5 60.4±13.2 57.7±20.7 54.0±14.4 <0.001 
Mean peak heart rate (standard deviation; bpm) 167.5±10.3 165.7±13.7 163.3±16.8 159.8±16.1 <0.001 
Mean HRR/peak heart rate % 38.8±6.9 36.4±8.0 34.5±12.6 33.5±8.1 <0.001 
Positive stress test (%) d 15 (26.3) 65 (25.2) 24 (14.6) 61 (37.0) 0.989 

Abbreviations: DBP, diastolic blood pressure; HR, heart rate; HRR, heart rate recovery; SBP, systolic blood pressure.

aSBP 120mm Hg–129mm Hg or DBP 80mm Hg–84mm Hg.

bSBP 130mm Hg–140mm Hg or DBP 85mm Hg–89mm Hg.

cSBP ≥140mm Hg or DBP ≥90mm Hg

dThe high frequency of positive stress tests was due to the fact that we considered a 0.1-mv change independent of the morphology in order to increase sensitivity.

Figure 1.

Bar Charts demonstrating the increasing prevalence of HRR in the slowest quartile (Q1) and decreasing prevalence of HRR in the fastest quartile (Q4) as blood pressure increases.

Figure 1.

Bar Charts demonstrating the increasing prevalence of HRR in the slowest quartile (Q1) and decreasing prevalence of HRR in the fastest quartile (Q4) as blood pressure increases.

Peak SBP and DBP among BP groups were significantly different, with the lowest readings in those with optimal BP and the highest readings in those with hypertension (P < 0.001). However, there was no significant difference between SBP and DBP recovery at 2 or 4 minutes among BP groups. SBP rise, the difference between peak SBP and SBP before exercise but standing, showed a marginally significant difference among the BP groups (P = 0.059). Other details can be found in Table 4.

Table 4.

Blood pressure and blood pressure response to stress testing

Characteristic Optimal BP Stage 1 PHT Stage 2 PHT HTN P value 
Mean resting SBP 106±6 118±5 129±3 139±14 <0.001 
Mean resting DBP 68±4 80±2 81±2  88±8 <0.001 
Peak SBP 160±25 170±23 180±21 189±26 <0.001 
Peak DBP 72±8 76±10 78±7 87±15 <0.001 
SBP rise 50 (30, 60) 50 (40, 60) 50 (40, 70) 60 (40, 70) 0.059 
DBP rise 0 (−10, 0) 0 (−10, 0) 0 (−10, 0) 0 (−10, 7.5) 0.366 
SBP decline at 2min post exercise 0 (−2.5, 10) 10 (0, 20) 10 (0, 20) 0 (−10, 20) 0.076 
SBP decline at 4min post exercise 30 (20, 40) 30 (20, 40) 40 (20, 40) 30 (20, 50) 0.218 
DBP decline at 2min post exercise 0 (−10, 0) 0 (−10, 0) 0 (0, 0) 0 (−10, 0) 0.176 
DBP decline at 4min post exercise 0 (−10, 0) 0 (−10, 0) 0 (0, 0) 0 (−10, 10) 0.106 
Exaggerated BP response (%) 6.3 6.0 13.3 39.3 <0.001 
Characteristic Optimal BP Stage 1 PHT Stage 2 PHT HTN P value 
Mean resting SBP 106±6 118±5 129±3 139±14 <0.001 
Mean resting DBP 68±4 80±2 81±2  88±8 <0.001 
Peak SBP 160±25 170±23 180±21 189±26 <0.001 
Peak DBP 72±8 76±10 78±7 87±15 <0.001 
SBP rise 50 (30, 60) 50 (40, 60) 50 (40, 70) 60 (40, 70) 0.059 
DBP rise 0 (−10, 0) 0 (−10, 0) 0 (−10, 0) 0 (−10, 7.5) 0.366 
SBP decline at 2min post exercise 0 (−2.5, 10) 10 (0, 20) 10 (0, 20) 0 (−10, 20) 0.076 
SBP decline at 4min post exercise 30 (20, 40) 30 (20, 40) 40 (20, 40) 30 (20, 50) 0.218 
DBP decline at 2min post exercise 0 (−10, 0) 0 (−10, 0) 0 (0, 0) 0 (−10, 0) 0.176 
DBP decline at 4min post exercise 0 (−10, 0) 0 (−10, 0) 0 (0, 0) 0 (−10, 10) 0.106 
Exaggerated BP response (%) 6.3 6.0 13.3 39.3 <0.001 

Peak SBP and peak DBP are presented as mean ± standard deviation. Other variables are presented as median (interquartile range). P values generated from analysis of variance (peak SBP, peak DBP) and Kruskal–Wallis tests (other variables). SBP rise = peak SBP – baseline (standing) SBP; DBP rise = peak DBP – baseline (standing) DBP. SBP decline = peak SBP – SBP at specified time interval; DBP decline = peak DBP – DBP at specified time interval.

Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; HTN, hypertension; PHT, prehypertension; SBP, systolic blood pressure.

HRR was found to be independent of peak SBP, SBP and DBP rise from baseline to peak, DBP decline from peak DBP at 2 and 4 minutes, and SBP decline at 2 minutes (P > 0.05; data not shown). There was a weak negative correlation between HRR and peak DBP (r = −0.14; P < 0.001), while there was a weak positive correlation between HRR and SBP decline at 4 minutes (Spearman rho = 0.10; P = 0.016).

Table 5 shows results for unadjusted and adjusted ORs (95% CI) for the association between delayed HRR and PHT. Compared with those with optimal BP, those with stage 1 PHT were 3 times more likely to be in the slowest recovery quartile than in the fastest recovery quartile adjusting for sex, age, smoking, and BMI (adjusted OR, 3.01; 95% CI, 1.05, 8.66). Similarly, those with stage 2 PHT had almost 4 times the likelihood of being in the slowest quartile compared with those in the highest quartile after adjusting for age, sex, smoking, and BMI (adjusted OR, 3.8; 95% CI,1.06, 13.56). Figure 2 shows a progressive increase in the likelihood (OR) of being in the slowest quartile (Q1) of HRR compared with the fastest quartile (Q4) with optimal BP as a reference. In a third model controlling for age, sex, BMI, cigarette smoking, diabetes, exercise capacity, SBP decline at 2 minutes, and SBP decline at 4 minutes, HRR was still strongly associated with both stages of PHT and hypertension (Table 5 and Figure 2).

Table 5.

Unadjusted and Adjusted Odds Ratios Comparing Heart Rate Recovery in Hypertensives and Prehypertensives to those with Optimal Blood Pressures

HRR quartile Q1 Q2 Q3 
Unadjusted OR (95% CI) Adjusted ORa (95% CI) Adjustedb OR (95% CI) Unadjusted OR (95% CI) Adjusteda OR (95% CI) Adjustedb OR (95% CI) Unadjusted OR (95% CI) Adjusteda OR (95% CI) Adjustedb OR (95% CI) 
Stage I prehypertensionc 2.77 (1.12, 6.8) 3.01 (1.05, 8.66) 4.02 (1.07, 14.92) 1.44 (0.71,2.93) 1.39 (0.62, 3.10) 1.02 (0.39, 2.68) 2.53 (1.16, 5.50) 4.41 (1.62, 12.03) 4.40 (1.33, 14.62) 
Stage II prehypertensiond 3.89 (1.39, 10.86) 3.80 (1.06, 13.56) 5.00 (1.02, 24.42) 2.40 (1.04,5.52) 2.44 (0.90, 6.60) 2.32 (0.68, 7.95) 2.14 (0.83,5.47) 5.64 (1.68, 9.00) 8.30 (1.88, 36.52) 
Hypertensione 8.6 (3.47, 21.5) 4.10 (1.37, 12.24)  3.92 (1.02, 15.02) 2.76 (1.32, 5.76) 1.40 (0.58, 3.37) 1.09 (0.39, 3.13) 3.19 (1.41, 7.21) 4.34 (1.47, 12.82) 3.95 (1.06, 14.74) 
HRR quartile Q1 Q2 Q3 
Unadjusted OR (95% CI) Adjusted ORa (95% CI) Adjustedb OR (95% CI) Unadjusted OR (95% CI) Adjusteda OR (95% CI) Adjustedb OR (95% CI) Unadjusted OR (95% CI) Adjusteda OR (95% CI) Adjustedb OR (95% CI) 
Stage I prehypertensionc 2.77 (1.12, 6.8) 3.01 (1.05, 8.66) 4.02 (1.07, 14.92) 1.44 (0.71,2.93) 1.39 (0.62, 3.10) 1.02 (0.39, 2.68) 2.53 (1.16, 5.50) 4.41 (1.62, 12.03) 4.40 (1.33, 14.62) 
Stage II prehypertensiond 3.89 (1.39, 10.86) 3.80 (1.06, 13.56) 5.00 (1.02, 24.42) 2.40 (1.04,5.52) 2.44 (0.90, 6.60) 2.32 (0.68, 7.95) 2.14 (0.83,5.47) 5.64 (1.68, 9.00) 8.30 (1.88, 36.52) 
Hypertensione 8.6 (3.47, 21.5) 4.10 (1.37, 12.24)  3.92 (1.02, 15.02) 2.76 (1.32, 5.76) 1.40 (0.58, 3.37) 1.09 (0.39, 3.13) 3.19 (1.41, 7.21) 4.34 (1.47, 12.82) 3.95 (1.06, 14.74) 

Reference groups are optimal blood pressure and Q4.

Abbreviations: CI, confidence interval; DBP, diastolic blood pressure; HRR, heart rate recovery; OR, odds ratio; SBP, systolic blood pressure.

aAdjusted for age, sex, body mass index, and smoking.

bAdjusted for age, sex, body mass index, smoking, diabetes mellitus, exercise capacity, blood pressure decline at 2 minutes, and blood pressure decline at 4 minutes.

cSBP 120mm Hg − 129mm Hg or DBP 80mm Hg − 84mm Hg.

dSBP 130mm Hg − 140mm Hg or DBP 85mm Hg − 89mm Hg.

eSBP ≥140mm Hg or DBP ≥90mm Hg.

Figure 2.

Unadjusted and Adjusted Odds Ratios Comparing Heart Rate Recovery in Hypertensives and Prehypertensives to those with Optimal Blood Pressures. Numbers on each bar indicates odds ratios All Odds Ratios are statistically significant at the P ≤ 0.05 level.

Figure 2.

Unadjusted and Adjusted Odds Ratios Comparing Heart Rate Recovery in Hypertensives and Prehypertensives to those with Optimal Blood Pressures. Numbers on each bar indicates odds ratios All Odds Ratios are statistically significant at the P ≤ 0.05 level.

DISCUSSION

In this study, both early and late PHT were strongly and independently associated with delayed HRR. This suggests that worsening of parasympathetic function occurs early in the development of hypertension.

It has been established that sympathetic overactivity is involved in the pathogenesis of hypertension.27,28 However, several studies have shown that reduction of cardiac parasympathetic control also plays a role in the development of hypertension.29–31 Emerging data suggest that parasympathetic dysfunction also contributes to the development of PHT and its transition to hypertension.12,32 In particular, one study demonstrated that parasympathetic dysfunction is present in individuals with normotension and a family history of hypertension.32

It has been demonstrated that parasympathetic activity is the principal determinant of HRR after exercise and that persons with delayed HRR have parasympathetic dysfunction.33 Apart from our study, we are aware of only one other study in which HRR has been examined in prehypertensive patients.23 The authors of that study noted that HRR among those with PHT was significantly lower than in normotensive controls (P = 0.02). However, when a HRR <18 bpm in the first minute was used as the definition of delayed HRR, there was no significant difference between those with PHT and those with normotension, probably because of low statistical power. They also did not demonstrate delay in HRR in early PHT. We found similar associations between delayed HRR and PHT. However, we also demonstrated an increasing likelihood of being in the quartile with the slowest HRR (compared with the fastest recovery quartile) as progression through different stages of hypertension occurs.The interplay among BP response, HRR, and PHT is poorly understood. However, abnormal BP response has been associated with cardiovascular events and mortality34 and with the development of hypertension in those with normal BP.35 In our study, both peak SBP and peak DBP were associated with baseline BP. Exaggerated BP response was greater in late stage (stage 2) PHT and hypertension, but there was no significant difference in frequency of exaggerated BP response across quartiles of HRR. Although the declines from peak BP at 2 and 4 minutes were not associated with baseline BP, we included SBP decline at 2 and 4 minutes in a separate model that included those in the initial model (age, sex, smoking, and BMI), exercise capacity (METs), and diabetes and still found significant associations between HRR and PHT.

The heart rate findings in this study are very important since measuring HRR is noninvasive, relatively simple, and does not require specialized training. It can be done without the need for the entire stress test protocol and can be included in readings from physical activity monitors. Our findings thus open the discussion of the clinical utility of HRR after exercise and cardiovascular risk management in the setting of PHT. In particular, the following questions need to be answered:

  • Does delayed HRR in those with optimal BP (<120/80mm Hg) or PHT predict progression to hypertension?

  • Should delayed HRR be only a marker of risk or a therapeutic target?

  • Should a normal HRR in PHT attract less aggressive pursuance of BP goals?

Due to its cross-sectional nature, this study cannot be used to determine a causal relationship between PHT and delayed HRR. Although serial baseline BP measurements were taken, these measurements were obtained at a single visit. In addition, ascertainment of covariates such as smoking, history of hypertension, or use of antihypertensive or lipid-lowering drugs was through self-report. Consequently, we cannot rule out the possibility of misclassification or misclassification bias. Our findings could have been impacted by white-coat hypertension or masked hypertension; however, we were unable to obtain home BP or ambulatory BP measurements to rule this out. We note that our study was conducted among asymptomatic participants and a largely male population. We speculate that most of the participants were male because there were more male executives at the time of the study. As such, our findings may not be generalizable to women or persons who have had a cardiovascular event.

In this population, stages of PHT are independently associated with delayed HRR, suggesting early autonomic dysfunction in the development of hypertension. Further studies are needed to determine what role parasympathetic dysfunction plays in the development of PHT, how useful the measure of HRR is in the prediction of progress to clinical hypertension, and what the optimal management strategies should be in persons with or without PHT and delayed HRR.

DISCLOSURE

The authors declared no conflict of interest.

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