Background
Methods
Study design and sample
Heart rate assessment
Definitions of cardiovascular risk factors and laboratory methods
Determination of vascular (endothelial) function by flow-mediated dilation and peripheral arterial tonometry
Data management and statistical analysis
Results
Relation between heart rate and sample characteristics
Groups of heart rate at rest | |||
---|---|---|---|
Heart rate [bpm] | < 53 | 53–75 | > 75 |
N
| 720 | 10,327 | 3,878 |
Sex (Women) | 32.1% (231) | 49.1% (5068) | 53.0% (2054) |
Age (years) | 56.9 ± 11.1 | 54.9 ± 11.1 | 54.7 ± 11.1 |
Cardiovascular risk factors
| |||
Diabetes mellitus | 8.6% (62) | 8.0% (822) | 12.9% (499) |
Arterial hypertension | 53.1% (382) | 46.5% (4799) | 57.6% (2234) |
Smoking | 17.8% (128) | 19.3% (1993) | 20.1% (779) |
Obesity | 22.6% (163) | 22.8% (2350) | 32.1% (1243) |
Dyslipidemia | 48.7% (350) | 43.2% (4449) | 46.4% (1791) |
Family history of MI/stroke | 23.6% (170) | 22.0% (2272) | 22.2% (860) |
Concomitant disease
| |||
CHF | 9.2% (66) | 7.0% (720) | 9.3% (359) |
CAD | 9.6% (68) | 4.5% (461) | 2.8% (107) |
MI | 6.1% (44) | 3.0% (310) | 2.1% (83) |
Stroke | 2.1% (15) | 1.8% (187) | 1.9% (74) |
AF | 18.5% (133) | 16.5% (1699) | 16.6% (643) |
PAD | 4.4% (31) | 3.1% (315) | 4.0% (153) |
COPD | 3.3% (24) | 4.7% (481) | 6.1% (238) |
CKD | 0.8% (6) | 1.0% (102) | 1.1% (43) |
Surrogate marker for cardiovascular disease
| |||
Heart rate [bpm] | 49.2 ± 3.0 | 65.1 ± 5.9 | 82.9 ± 7.2 |
BMI (kg/m2) | 27.2 ± 4.3 | 27.1 ± 4.7 | 28.1 ± 5.6 |
SBP (mmHg) | 131.3 ± 17.4 | 130.4 ± 17.2 | 134.8 ± 17.7 |
DBP (mmHg) | 77.7 ± 8.7 | 81.5 ± 9.1 | 86.2 ± 9.6 |
MAP (mmHg) | 95.6 ± 10.2 | 97.8 ± 10.8 | 102.4 ± 11.4 |
HbA1c (%) | 5.57 ± 0.56 | 5.54 ± 0.65 | 5.67 ± 0.82 |
LDL (mg/dl) | 132.7 ± 33.5 | 138.8 ± 35.2 | 140.6 ± 36.4 |
HDL (mg/dl) | 55.9 ± 14.9 | 57.7 ± 15.6 | 56.7 ± 15.8 |
Triglycerides (mg/dl) | 122.6 ± 65.8 | 120.2 ± 71.4 | 133.7 ± 98.1 |
FMD (%) | 7.09 ± 4.44 | 8.18 ± 5.19 | 8.30 ± 5.54 |
Baseline brachial artery diameter | 4.57 ± 0.82 | 4.32 ± 0.85 | 4.28 ± 0.86 |
SI (m/s) | 7.30 ± 2.36 | 7.53 ± 2.26 | 7.63 ± 2.03 |
RI | 74.72 ± 15.89 | 67.10 ± 15.42 | 58.80 ± 15.64 |
AI (%) | 31.37 ± 25.13 | 19.30 ± 20.70 | 9.53 ± 15.69 |
RHI | 0.62 ± 0.42 | 0.65 ± 0.42 | 0.65 ± 0.41 |
Baseline pulse amplitude | 620.2 ± 471.0 | 568.3 ± 444.9 | 546.6 ± 407.0 |
Troponin I > 0.02* (ng/mL) | 6.9% (18) | 3.2% (106) | 4.5% (57) |
Endothelin 1* (pmol/l) | 59.4 (50.9/68.3) | 58.9 (50.2/67.7) | 59.3 (51.0/69.2) |
CT-proAVP* (pmol/l) | 2.75 (1.75/4.25) | 2.73 (1.79/4.31) | 2.96 (1.79/4.84) |
MR-proADM* (nmol/L) | 0.47 (0.40/0.56) | 0.46 (0.39/0.53) | 0.47 (0.40/0.57) |
NT-proBNP* (pg/mL) | 86.47 (39.88/192.43) | 62.44 (29.48/125.57) | 55.95 (24.06/109.96) |
MR-proANP* (pmol/l) | 89.2 (65.8/121.0) | 67.6 (50.7/91.0) | 57.0 (43.1/78.6) |
Age- and sex-specific distribution of heart rate in the population
Heart rate and all-cause mortality
Adjustment for age and sex | Additional adjustment for cardiovascular risk factors and concomitant diseases | Additional adjustment for medication | ||||
---|---|---|---|---|---|---|
Hazard ratio per 10 bpm (95% CI) | P value | Hazard Ratio per 10 bpm (95% CI) | P value | Hazard ratio per 10 bpm (95% CI) | P value | |
Heart rate below 64 bpm | 1.54 (1.22; 1.95) |
0.00029
| 1.44 (1.12; 1.85) |
0.0039
| 1.36 (1.06; 1.76) |
0.016
|
Heart rate above 64 bpm | 1.35 (1.25; 1.46) | < 0.0001 | 1.30 (1.20; 1.41) | < 0.0001 | 1.30 (1.19; 1.41) | < 0.0001 |
Cardiovascular risk correlates of heart rate
Heart rate and subclinical markers of cardiovascular disease
Adjusted for age and sex Beta estimate (95% CI) | P value | Additionally adjusted for cardiovascular risk factors and concomitant diseases Beta estimate (95% CI) | P value | Additionally adjusted for medication Beta estimate (95% CI) | P value | |
---|---|---|---|---|---|---|
(1) Humoral biomarkers | ||||||
Heart rates < 53 bpm | ||||||
Troponin I | 0.21 (0.12; 0.30) | < 0.0001 | 0.19 (0.10; 0.28) | < 0.0001 | 0.20 (0.11; 0.29) | < 0.0001 |
Endothelin 1 | − 0.013 (− 0.040; 0.015) | 0.37 | − 0.0088 (− 0.036; 0.018) | 0.53 | − 0.020 (− 0.048; 0.0071) | 0.15 |
CT-proAVP | − 0.14 (− 0.23; − 0.059) |
0.00097
| − 0.14 (− 0.22; − 0.048) |
0.0023
| − 0.15 (− 0.23; − 0.058) |
0.0012
|
MR-proADM | 0.0086 (− 0.020; 0.037) | 0.55 | 0.024 (− 0.0017; 0.050) | 0.067 | 0.0078 (− 0.018; 0.034) | 0.55 |
NT-proBNP | 0.44 (0.30; 0.58) | < 0.0001 | 0.39 (0.25; 0.53) | < 0.0001 | 0.24 (0.11; 0.38) |
0.00055
|
MR-proANP | 0.32 (0.27; 0.37) | < 0.0001 | 0.30 (0.25; 0.35) | < 0.0001 | 0.22 (0.17; 0.27) | < 0.0001 |
Heart rates > 75 bpm | ||||||
Troponin I | − 0.023 (− 0.068; 0.022) | 0.31 | − 0.038 (− 0.084; 0.0075) | 0.10 | − 0.039 (− 0.086; 0.0073) | 0.098 |
Endothelin 1 | 0.020 (0.0064; 0.034) |
0.0043
| 0.0097 (− 0.0044; 0.024) | 0.18 | 0.014 (− 0.00037; 0.028) | 0.056 |
CT-proAVP | 0.14 (0.092; 0.18) | < 0.0001 | 0.10 (0.059; 0.15) | < 0.0001 | 0.11 (0.069; 0.16) | < 0.0001 |
MR-proADM | 0.035 (0.021; 0.050) | < 0.0001 | 0.0086 (− 0.0048; 0.022) | 0.21 | 0.016 (0.0025; 0.029) |
0.020
|
NT-proBNP | − 0.21 (− 0.28; − 0.14) | < 0.0001 | − 0.21 (− 0.28; − 0.14) | < 0.0001 | − 0.13 (− 0.20; − 0.056) |
0.00047
|
MR-proANP | − 0.18 (− 0.20; − 0.15) | < 0.0001 | − 0.17 (− 0.20; − 0.15) | < 0.0001 | − 0.13 (− 0.16; − 0.11) | < 0.0001 |
(2) Vascular biomarkers | ||||||
Heart rates < 53 bpm | ||||||
Flow-mediated dilation | − 0.34 (− 0.74; 0.059) | 0.095 | − 0.42 (− 0.82; − 0.015) |
0.042
| − 0.41 (− 0.81; 0.00075) | 0.050 |
Baseline brachial artery diameter | 0.0086 (− 0.038; 0.055) | 0.71 | 0.023 (− 0.022; 0.068) | 0.31 | 0.029 (− 0.017; 0.074) | 0.22 |
Reactive hyperemia index | 0.030 (− 0.0036; 0.064) | 0.080 | 0.018 (− 0.015; 0.051) | 0.30 | 0.026 (− 0.0075; 0.059) | 0.013 |
Baseline pulse amplitude | − 17.4 (− 51.6; 16.7) | 0.32 | − 4.79 (− 38.2; 28.6) | 0.78 | − 6.34 (− 40.1; 27.5) | 0.71 |
Reflection index | 7.49 (6.32; 8.67) | < 0.0001 | 7.40 (6.21; 8.59) | < 0.0001 | 7.45 (6.24; 8.66) | < 0.0001 |
Augmentation index | 15.9 (14.4; 17.4) | < 0.0001 | 15.5 (14.0; 16.9) | < 0.0001 | 15.2 (13.7; 16.7) | < 0.0001 |
Stiffness index | − 0.67 (− 0.83; − 0.51) | < 0.0001 | − 0.65 (− 0.82; − 0.49) | < 0.0001 | − 0.58 (− 0.74; − 0.41) | < 0.0001 |
Heart rates > 75 bpm | ||||||
Flow-mediated dilation | − 0.012 (− 0.21; 0.18) | 0.90 | 0.19 (− 0.0058; 0.39) | 0.057 | 0.22 (0.017; 0.42) |
0.033
|
Baseline brachial artery diameter | 0.048 (− 0.018; 0.027) | 0.68 | − 0.037 (− 0.060; − 0.015) |
0.00097
| − 0.043 (− 0.065; − 0.020) |
0.00023
|
Reactive hyperemia index | − 0.020 (− 0.036; − 0.0030) |
0.021
| − 0.00012 (− 0.017; 0.016) | 0.99 | − 0.0038 (− 0.021; 0.013) | 0.65 |
Baseline pulse amplitude | − 7.27 (− 24.1; 9.58) | 0.40 | − 26.2 (− 42.8; − 9.63) |
0.0020
| − 26.2 (− 43.1; − 9.31) |
0.0024
|
Reflection index | − 8.15 (− 8.70; − 7.59) | 0.11 | − 8.34 (− 8.91; − 7.77) | < 0.0001 | − 8.48 (− 9.06; − 7.90) | < 0.0001 |
Augmentation index | − 11.1 (− 11.8; − 10. 3) | < 0.0001 | − 10.9 (− 11.7; − 10.2) | < 0.0001 | − 10.8 (− 11.6; − 10.1) | < 0.0001 |
Stiffness index | 0.23 (0.15; 0.31) | < 0.0001 | 0.17 (0.090; 0.25) | < 0.0001 | 0.12 (0.044; 0.20) |
0.0023
|