Table 1
Algorithm for classification of CAN (CAN score).
| Tests | Point 0 | Point 0.5 | Point 1 |
|---|---|---|---|
| Resting heart rate | <100 beats/min | 100–110 beats/min | >110 beats/min |
| Postural hypotension (fall in systolic blood pressure) | <20 mmHg | 20–30 mmHg | >30 mmHg |
| Valsalva ratio | >1.2 | 1.2–1.10 | <1.10 |
| Heart rate variability on deep breathing | >15 beats/min | 15–10 beats/min | <10 beats/min |
| Increase in diastolic blood pressure during sustained handgrip | >15 mmHg | 15–10 mmHg | <10 mmHg |
[i] CAN: Cardiovascular autonomic neuropathy.
Figure 1
Study profile.
Table 2
Baseline demographic and clinical characteristics by CAN status.
| Characteristic | Total cohort (N = 299) | Positive for CAN (N = 156) | No evidence of CAN (N = 143) | P value |
|---|---|---|---|---|
| Age, in years, mean (SD) | 50.1 (±9.8) | 52.8 (±8.7) | 47.2 (±10.2) | <0.001 |
| Female sex (%) | 208 (69.6) | 122 (78.2) | 86 (60.1) | 0.001 |
| Ever attended school, yes (%) | 233 (77.9) | 115 (73.7) | 118 (82.5) | 0.067 |
| Occupation | ||||
| Peasant (%) | 175 (58.5) | 103 (66.0) | 72 (50.4) | 0.006 |
| Student (%) | 6 (2.0) | 2 (1.3) | 4 (2.8) | 0.351 |
| Businessman (woman) (%) | 64 (21.4) | 29 (18.6) | 35 (24.5) | 0.215 |
| Civil servant (%) | 51 (17.1) | 26 (16.7) | 25 (17.5) | 0.851 |
| Ever smoked, yes (%) | 70 (23.4) | 37 (23.7) | 32 (22.4) | 0.783 |
| Currently smoking, yes (%) | 18 (25.7) | 11 (29.0) | 7 (21.9) | 0.500 |
| Duration of diabetes in years, mean (SD) | 5.8 (±5.9) | 7.5 (±6.9) | 3.9 (±3.9) | <0.001 |
| BMI (kg/m2), mean (SD) | 27.4 (±5.6) | 27.5 (±5.9) | 27.3 (±5.2) | 0.685 |
| Waist circumference in cm, mean (SD) | 98.2 (±13.6) | 99.9 (±14.3) | 96.4 (±12.7) | 0.025 |
| History of vigorous physical activity (≥600 METS/Week) (%) | 173 (57.9) | 89 (57.1) | 84 (58.7) | 0.087 |
| Fasting blood sugar in mmol/L, mean (SD) | 11.2 (±4.8) | 11.8 (±5.2) | 10.5 (±4.3) | 0.021 |
| HbA1c (%), mean(SD) | 9.7 (±6.7) | 9.7 (±2.5) | 9.6 (± 2.7) | 0.506 |
| Resting heart rate in beats/min, mean (SD) | 76.6 (±13.1) | 79.2 (±14.7) | 73.6 (±10.4) | <0.001 |
| Systolic blood pressure in mmHg, mean (SD) | 141.7 (±22.6) | 148.6 (±23.2) | 134.2 (±19.4) | <0.001 |
| Diastolic blood pressure in mmHg, mean (SD) | 87.1 (±10.7) | 88.8 (±10.7) | 85.4 (±10.5) | 0.006 |
| Pulse pressure in mmHg, mean (SD) | 54.6 (±17.8) | 59.9 (±19.4) | 48.8 (±13.8) | <0.001 |
| Mean arterial pressure (mmHg) | 105.3 (±13.3) | 108.7 (±13.1) | 101.6 (±12.5) | <0.001 |
| Retinopathy | <0.001 | |||
| None (%) | 231 (77.3) | 106 (68.0) | 125 (87.4) | |
| Non-proliferative (%) | 53 (17.7) | 35 (22.4) | 18 (12.6) | |
| Proliferative (%) | 15 (5.0) | 15 (9.6) | 0 (0.0) | |
| History of neuropathy symptoms in past 6 months | ||||
| Palpitations, yes (%) | 149 (49.8) | 93 (59.6) | 56 (39.2) | <0.001 |
| Fainting or blackouts, yes (%) | 114 (38.1) | 63 (40.4) | 51 (35.7) | 0.401 |
| ‘Dead feeling’, pricking or burning sensation in the feet, yes (%) | 183 (61.2) | 105 (67.3) | 78 (54.6) | 0.024 |
| QTc interval (ms), mean (SD) | 428.4 (±22.3) | 438.4 (±22.0) | 417.5 (±16.8) | <0.001 |
[i] SD: Standard deviation; CAN: Cardiovascular Autonomic Neuropathy; MET: Metabolic Equivalent Task.
Table 3
Prevalence of CAN by the different assessment methods.
| N = 299 | ||
|---|---|---|
| Resting tachycardia (pulse rate ≥100 bpm) | 17 | 5.7 |
| Abnormal postural index (≤1.0) | 40 | 13.4 |
| HRV: Reduced E/I ratio with deep breathing (<15 bpm), | 125 | 41.8 |
| Valsalva ratio: (<1.2), (N = 284)* | 52 | 18.3 |
| Postural hypotension | 52 | 17.4 |
| Diastolic BP response to sustained hand grip (<15 mmHg) | 108 | 36.1 |
[i] HRV: Heart rate variability; E/I: Expiration to inspiration ratio.
* Sample size is less by 15 participants who had proliferative retinopathy and were excluded from the valsalva maneuver.
Table 4
Prevalence of CAN by severity (Classification of CAN).
| N = 299 | ||
|---|---|---|
| Absent | 143 | 47.8 |
| Early | 88 | 29.4 |
| Definite/Confirmed | 61 | 20.4 |
| Severe/Advanced | 7 | 2.3 |
| TOTAL | 299 | 100.0 |
Figure 2
Graph showing variation of prevalence of CAN by severity with age.
Table 5
Demographic and clinical factors correlated with CAN.
| % CAN positive | Univariable Analysis | Multivariable Analysis | p value | ||
|---|---|---|---|---|---|
| Characteristic | n/N (%) | OR 95%CI | p value | aOR 95%CI | |
| Age category(years) | |||||
| <35 | 7/29 (24.1) | Ref | Ref | ||
| 35–50 | 39/86 (45.4) | 2.61 (1.01–6.75) | 0.048 | 2.10 (0.77-5.74) | 0.147 |
| 51–65 | 110/184 (59.8) | 4.67 (1.90–11.49) | 0.001 | 3.48 (1.35–8.99) | 0.010 |
| Sex | |||||
| Male | 34/91 (37.4) | Ref | Ref | ||
| Female | 122/208 (58.7) | 2.38 (1.43–3.95) | 0.001 | 1.85 (0.94-3.66) | 0.076 |
| Duration of diabetes in years | |||||
| <5years | 74/170 (43.5) | Ref | Ref | ||
| 5–9 years | 38/76 (50.0) | 1.30 (0.75–2.23) | 0.347 | 1.04 (0.58–1.88) | 0.893 |
| 10 years and above | 44/53 (83.0) | 6.34 (2.91–13.81) | <0.001 | 4.09 (1.78–9.38) | 0.001 |
| Fasting blood sugar category | |||||
| ≤7.0 mmol/L | 24/60 (40.0) | Ref | Ref | ||
| >7.0 mmol/L | 132/239 (55.2) | 1.85 (1.04–3.29) | 0.036 | 1.62 (0.86–3.04) | 0.135 |
| Blood pressure category | |||||
| ≤130/80 mmHg | 18/60 (30.0) | Ref | |||
| >130/80 mmHg | 105/168 (62.5) | 3.89 (2.06–7.33) | <0.001 | ||
| Waist circumference | |||||
| Normal fat distribution | 26/62 (41.9) | Ref | Ref | ||
| Moderate central fat distribution | 19/48 (39.6) | 0.91 (0.42–1.95) | 0.804 | 0.66 (0.28–1.55) | 0.339 |
| High central fat accumulation | 111/189 (58.7) | 1.97 (1.10–3.53) | 0.022 | 1.16 (0.53–2.52) | 0.709 |
| Retinopathy | |||||
| Absent | 106/231 (45.9) | Ref | Ref | ||
| Present | 50/68 (73.5) | 3.28 (1.80–5.95) | <0.001 | 2.25 (1.16–4.34) | 0.016 |
| History of Palpitations in past 6 months | |||||
| No | 63/150 (42.0) | Ref | |||
| Yes | 93/149 (62.4) | 2.29 (1.44–3.65) | <0.001 | ||
| Symptoms of distal peripheral neuropathy | |||||
| No | 51/116 (44.0) | Ref | |||
| Yes | 105/183 (57.4) | 1.72 (1.07–2.74) | 0.024 | ||
| Resting heart rate | |||||
| ≤85 beats/min | 102/227(44.9) | Ref | |||
| >85 beats/min | 54/72 (75.0) | 3.68 (2.03–6.66) | <0.001 | ||
| QTc interval | |||||
| ≤440 ms | 74/213 (34.7) | Ref | |||
| >440 ms | 82/86 (95.4) | 38.51 (13.58–109.21) | <0.001 |
[i] aOR: Adjusted Odds Ratio; Ref: Reference Category; CI: Confidence interval; QTc: Heart rate corrected QT.