Simone Theilade

Arterial Stiffness Is Associated With Cardiovascular, Renal, Retinal, and Autonomic Disease in Type 1 Diabetes

OBJECTIVE In patients with type 1 diabetes, we investigated the association between arterial stiffness and diabetes complications. RESEARCH DESIGN AND METHODS This was a cross-sectional study including 676 Caucasian patients with type 1 diabetes (374 [55%] men, aged 54 ± 13 years [mean ± SD]) and 51 nondiabetic controls (28 [55%] men, aged 47 ± 13 years). Aortic pulse wave velocity (PWV) was measured with SphygmoCor (AtCor Medical, Sydney, Australia) for 635 patients and all 51 controls. RESULTS PWVs (mean ± SD) in patients and controls were 10.4 ± 3.4 and 7.6 ± 1.9 m/s, respectively (P < 0.001). After multivariate adjustment, PWV correlated with age, diabetes duration, urinary albumin excretion rate, heart rate, and blood pressure (P < 0.05 for all). ANCOVA was used for comparisons between groups and adjusted for gender, age, estimated glomerular filtration rate, heart rate, HbA1c, and 24-h mean arterial pressure. PWVs in normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 9.5 ± 3.2, 11.0 ± 3.6, and 11.4 ± 3.0 m/s, respectively (adjusted P < 0.001). PWV in patients with previous cardiovascular disease, versus patients without, was 12.1 ± 3.5 vs. 10.0 ± 3.2 m/s, respectively (adjusted P < 0.001). PWVs in patients with high (≥140/90 mmHg) versus intermediate (130–40/80–89 mmHg) and low (<130/80 mmHg) blood pressure were 11.8 ± 3.6, 10.0 ± 3.0, and 9.8 ± 3.3 m/s, respectively (adjusted P < 0.001). Furthermore, PWV increased with increasing degree of retinopathy: 8.0 ± 2.5 m/s (nil), 10.0 ± 2.8 m/s (simplex), 12.1 ± 3.5 m/s (proliferative), and 12.7 ± 2.4 m/s (blind), respectively (adjusted P < 0.001). Finally, PWV increased with abnormal heart rate variability: 11.5 ± 3.3 m/s vs. 10.1 ± 3.1 m/s (borderline) and 8.1 ± 2.1 m/s (normal) (adjusted P = 0.027). CONCLUSIONS Arterial stiffness increased with presence and duration of type 1 diabetes. Furthermore, PWV increased with all the investigated diabetes complications (cardiovascular, renal, retinal, and autonomic disease) independently of other risk factors.

Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes.

Arterial stiffness and endothelial dysfunction independently and synergistically predict cardiovascular and renal outcome in patients with type 1 diabetes.

Diabet. Med. 29, 990–994 (2012)

Ambulatory Tonometric Blood Pressure Measurements in Patients with Diabetes

BACKGROUND Arterial tonometry is a novel technique for measuring ambulatory blood pressure (AMBP). The watch-like device BPro(®) (HealthSTATS International, Singapore) captures radial pulsewave reflection and calculates brachial blood pressure (BP). In this study we investigate if arterial tonometry is applicable and reliable in patients with diabetes. SUBJECTS AND METHODS We compared tonometric (BPro) to cuff-based oscillometric and auscultatoric BPs (Takeda model TM2421, A&D Medical, Tokyo, Japan) in 25 Caucasian patients with type 1 or type 2 diabetes. Patients were seen twice within 2 weeks. At visit 1, a 15-min rest was followed by the recording of three cuff-based BPs and 2-min continuous tonometric BPs. At both visits 24-h AMBP measurements were recorded with the BPro device. RESULTS At Visit 1, auscultatoric BP (mean±SD) was 136±19/72±8 mm Hg versus 138±19/78±8 mm Hg with the tonometric device. Visit 1 AMBP was 131±20/76±9 mm Hg versus 131±12/75±9 mm Hg at Visit 2. Mean 24-h AMBP, daytime BP, nighttime BP, and dipping at the two visits were similar (P>0.40). Linear and intraclass correlations coefficients between auscultatoric and tonometric systolic and diastolic BP were r=0.86 and 0.65, respectively (P<0.001 for both), and r=0.83 and 0.77, respectively (P<0.001 for both). The mean differences between devices were 1.9±10 and 5.5±6.6 mm Hg for systolic and diastolic BP, respectively. CONCLUSIONS In patients with diabetes tonometric and cuff-based BPs are comparable, and tonometric AMBPs are reproducible and feasible.

Central hemodynamics are associated with cardiovascular disease and albuminuria in type 1 diabetes.

BACKGROUND We sought to investigate associations between central hemodynamic parameters (estimated from radial pulse wave analyses (PWAs)), cardiovascular disease (CVD), and albuminuria in type 1 diabetes. METHODS We conducted an observational study of 636 type 1 diabetes patients. Central hemodynamics were measured by PWA as central aortic systolic pressure (CASP), central aortic pulse pressure (CPP), central aortic diastolic pressure (CADP), and subendocardial viability ratio (SEVR). CVD included revascularization, myocardial infarction, peripheral arterial disease, and stroke. Albuminuria was urinary albumin excretion rate ≥30 mg/24 hours. We computed standardized odds ratios (ORs) adjusted for sex, age, mean arterial pressure (MAP), heart rate, height, estimated glomerular filtration rate, glycated hemoglobin (HbA1c) total cholesterol, antihypertensive medication, and smoking. At follow-up, development of end-stage renal disease (ESRD) and mortality was traced through electronic medical records. RESULTS Patients were aged a mean of 54±13 years, and 289 (45%) were women. The mean ± SD was 118±17 mm Hg for CASP, 75±10 mm Hg for CADP, 43±14 mm Hg for CPP, and 150±32 for SEVR. In fully adjusted models, increased CASP and CPP and decreased CADP and SEVR were associated with presence of CVD (n = 132; P ≤ 0.02) and presence of albuminuria (n = 335; P < 0.001). During follow-up, median (range) (2.8 (0.7-3.8) years), SEVR predicted ESRD or mortality combined (n = 26) after adjustment for sex, age, and MAP (P = 0.001), whereas CASP, CPP, and CADP did not (P ≥ 0.13). CONCLUSIONS In type 1 diabetes patients, increased CASP and CPP and decreased CADP and SEVR were independently associated with history of CVD and albuminuria. Furthermore, SEVR predicted mortality and ESRD during follow-up. Future studies are needed to determine whether targeting central hemodynamics improves outcome.

Evaluation of placental growth factor and soluble Fms-like tyrosine kinase 1 as predictors of all-cause and cardiovascular mortality in patients with Type 1 diabetes with and without diabetic nephropathy.

Diabet. Med. 29, 337–344 (2012)

Tonometric devices for central aortic systolic pressure measurements in patients with type 1 diabetes: comparison of the BPro and SphygmoCor devices.

ObjectiveCentral blood pressure may be a better risk marker than brachial blood pressure and can be measured noninvasively by tonometric devices. We investigate whether tonometric measurements are feasible in patients with diabetes and whether the degree of albuminuria or increased arterial stiffness affects measurements. Patients and methodsIn 676 patients with type 1 diabetes, comparison of central aortic systolic pressure (CASP) measurements by the BPro and the SphygmoCor devices were made. The BPro device can obtain both office and 24-h measurements, whereas the SphygmoCor device is an accepted device for CASP measurements. ResultsMeasurements of CASP with both BPro and SphygmoCor were available in 598 (88.5%) patients (mean age 54 years; mean diabetes duration 33 years; 45.2% women), and mean±SD of CASP was 122±17 and 118±17 mmHg, respectively (P<0.001). Linear and intraclass correlation coefficients between CASP estimated from BPro and SphygmoCor were r equal to 0.96 and 0.95 (P<0.001 for both). The mean±SD difference between devices was 3.6±4.8 mmHg (P<0.001).Analyses according to the level of albuminuria or degree of arterial stiffness were confirmatory. ConclusionIn patients with type 1 diabetes, tonometric measurements of CASP with BPro and SphygmoCor showed strong correlations, although values differed by ∼4 mmHg between devices. Level of CASP, arterial stiffness, and degree of albuminuria did not interfere with the agreement between devices.In addition, the BPro device can obtain 24-h measurements and may thus be useful to assess the diurnal patterns of CASP.

Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia-the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT)

Pulse pressure (PP) remains an elusive cardiovascular risk factor with inconsistent findings. We clarified the prognostic value in patients with type 2 diabetes, chronic kidney disease (CKD) and anemia in the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin alfa) Therapy. In 4038 type 2 diabetes patients, darbepoetin alfa treatment did not affect the primary outcome. Risk related to PP at randomization was evaluated in a multivariable model including age, gender, kidney function, cardiovascular disease (CVD) and other conventional risk factors. End points were myocardial infarction (MI), stroke, end stage renal disease (ESRD) and the composite of cardiovascular death, MI or hospitalization for myocardial ischemia, heart failure or stroke (CVD composite). Median (interquartile range) age, gender, eGFR and PP was 68 (60–75) years, 57.3% women, 33 (27–42) ml min−1 per 1.73 m2 and 60 (50–74) mm Hg. During 29.1 months (median) follow-up, the number of events for composite CVD, MI, stroke and ESRD was 1010, 253, 154 and 668. In unadjusted analyses, higher quartiles of PP were associated with higher rates per 100 years of follow-up of all end points (P⩽0.04), except stroke (P=0.52). Adjusted hazard ratios (95% confidence interval) per one quartile increase in PP were 1.06 (0.99–1.26) for MI, 0.96 (0.83–1.11) for stroke, 1.01 (0.94–1.09) for ESRD and 1.01 (0.96–1.07) for CVD composite. Results were similar in continuous analyses of PP (per 10 mm Hg). In patients with type 2 diabetes, CKD and anemia, PP did not independently predict cardiovascular events or ESRD. This may reflect confounding by aggressive antihypertensive treatment, or PP may be too rough a risk marker in these high-risk patients.

Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping: a randomised, placebo-controlled, double-blind cross-over trial

Objectives Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping. Setting Secondary healthcare unit in Copenhagen, Denmark. Participants 24 normoalbuminuric patients with T1D with CAN and non-dipping were included, consisting of mixed gender and Caucasian origin. Mean±SD age, glycosylated haemoglobin and diabetes duration were 60±7 years, 7.9±0.7% (62±7 mmol/mol) and 36±11 years. Interventions In this randomised, placebo-controlled, double-blind cross-over study, the patients were treated for 12 weeks with either MD (20 mg enalapril in the morning and placebo at bedtime) or BD (placebo in the morning and 20 mg enalapril at bedtime), followed by 12 weeks of switched treatment regimen. Primary and secondary outcome measures Primary outcome was altered dipping of nocturnal BP. Secondary outcomes included a measurable effect on other cardiovascular risk factors than BP, including left ventricular function (LVF). Results Systolic BP dipping increased 2.4% (0.03–4.9%; p=0.048) with BD compared to MD of enalapril. There was no increase in mean arterial pressure dipping (2.2% (−0.1% to 4.5%; p=0.07)). No difference was found on measures of LVF (p≥0.15). No adverse events were registered during the study. Conclusions We demonstrated that patients with T1D with CAN and non-dipping can be treated with an ACE inhibitor at night as BD as opposed to MD increased BP dipping, thereby diminishing the abnormal BP profile. The potentially beneficial effect on long-term cardiovascular risk remains to be determined. Trial registration number EudraCT2012-002136-90; Post-results.

Discrepancy Between Tonometric Ambulatory and Cuff-Based Office Blood Pressure Measurements in Patients With Type 1 Diabetes

J Clin Hypertens (Greenwich). 2012;14:686–693. ©2012 Wiley Periodicals, Inc.