Astrup Anne Sofie, Tarnow Lise, Rossing Peter, Hansen Birgitte V, Hilsted Jannik, Parving Hans-Henrik
Steno Diabetes Center, Niels Steensensvej 2, 2820 Gentofte, Denmark.
Diabetes Care. 2006 Feb;29(2):334-9. doi: 10.2337/diacare.29.02.06.dc05-1242.
Cardiac autonomic neuropathy (CAN) has been associated with a poor prognosis in patients with diabetes. Because CAN is common in patients with diabetic nephropathy, we evaluated the predictive value of CAN in type 1 diabetic patients with and without diabetic nephropathy.
In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy and a matched group of 191 patients with long-standing type 1 diabetes and normoalbuminuria were followed for 10.1 years (range 0.0-10.3 years). At baseline, CAN was assessed by heart rate variation (HRV) during deep breathing. HRV was evaluated as a predictor of the primary end point: cardiovascular morbidity and mortality. As secondary end points, all-cause mortality and the influence of HRV on progression of diabetic nephropathy (decline in glomerular filtration rate [GFR]) was evaluated.
During the follow-up, 79 patients (40%) with nephropathy reached the combined primary end point vs. 19 patients (10%) with normoalbuminuria (log-rank test, P < 0.0001). The unadjusted hazard ratio (HR) for reaching the primary end point when having an abnormal HRV (< or =10 bpm) measured at baseline compared with a normal HRV was 7.7 (range 1.9-31.5; P = 0.004) in patients with nephropathy. Similarly in the normoalbuminuric patients, the unadjusted HR was 4.4 (1.4-13.6; P = 0.009). In patients with nephropathy, abnormal HRV was significantly associated with fatal and nonfatal cardiovascular disease after adjustment for cardiovascular risk factors. The adjusted HR for reaching the primary end point in a patient with nephropathy and an abnormal HRV was 6.4 (1.5-26.3, P = 0.010), as compared with a normal HRV. The unadjusted HR for dying when having an abnormal HRV compared with a normal HRV was 3.3 (95% CI 1.0-10.7; P = 0.043) in patients with diabetic nephropathy. After adjustment for confounding factors, the impact of HRV on all-cause mortality in patients with nephropathy was no longer significant (P = 0.293). There was no relationship between abnormal HRV and rate of decline in GFR.
HRV is an independent risk factor for cardiovascular morbidity and mortality in type 1 diabetic patients with nephropathy.
心脏自主神经病变（CAN）与糖尿病患者的不良预后相关。由于CAN在糖尿病肾病患者中很常见，我们评估了CAN在1型糖尿病肾病患者和非糖尿病肾病患者中的预测价值。
在一项前瞻性观察性随访研究中，对197例1型糖尿病肾病患者和191例长期1型糖尿病且尿白蛋白正常的匹配组患者进行了10.1年（范围0.0 - 10.3年）的随访。在基线时，通过深呼吸时的心率变异性（HRV）评估CAN。HRV被评估为主要终点的预测指标：心血管发病率和死亡率。作为次要终点，评估全因死亡率以及HRV对糖尿病肾病进展（肾小球滤过率[GFR]下降）的影响。
在随访期间，79例（40%）肾病患者达到了综合主要终点，而19例（10%）尿白蛋白正常的患者达到该终点（对数秩检验，P < 0.0001）。肾病患者中，与正常HRV相比，基线时HRV异常（<或 = 10次/分钟）时达到主要终点的未调整风险比（HR）为7.7（范围1.9 - 31.5；P = 0.004）。同样，在尿白蛋白正常的患者中，未调整的HR为4.4（1.4 - 13.6；P = 0.009）。在肾病患者中，调整心血管危险因素后，异常HRV与致命和非致命心血管疾病显著相关。与正常HRV相比，肾病且HRV异常的患者达到主要终点的调整后HR为6.4（1.5 - 26.3，P = 0.010）。糖尿病肾病患者中，与正常HRV相比，HRV异常时死亡的未调整HR为3.3（95%CI 1.0 - 10.7；P = 0.043）。调整混杂因素后，HRV对肾病患者全因死亡率的影响不再显著（P = 0.293）。HRV异常与GFR下降率之间无关联。
HRV是1型糖尿病肾病患者心血管发病率和死亡率的独立危险因素。
