Coronary and extra-coronary artery calcium scores as predictors of cardiovascular events and mortality in chronic kidney disease stages 1-5: a prospective cohort study.

BACKGROUND: Vascular calcification is a known risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, since there is a lack of studies examining several arterial regions at a time, we aimed to evaluate the risk of major adverse cardiovascular events (MACE) and all-cause mortality according to calcium scores in five major arterial sites. METHODS: This was a prospective study of 580 patients from the Copenhagen CKD Cohort. Multidetector computed tomography of the coronary and carotid arteries, the thoracic aorta, the abdominal aorta and the iliac arteries was used to determine vascular calcification at baseline. Calcium scores were divided into categories: 0, 1-100, 101-400 and >400. RESULTS: During the follow-up period of 4.1 years a total of 59 cardiovascular events and 64 all-cause deaths occurred. In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, hypertension, diabetes mellitus, hypercholesterolemia and smoking, only the coronary and carotid arteries, and the thoracic aorta were independent predictors of the designated endpoints. When examining the potential of calcification in the five arterial sites for predicting MACE, the difference in C-statistic was also most pronounced in these three sites, at 0.21 [95% confidence interval (CI) 0.16%-0.26%, P < .001], 0.26 (95% CI 0.22%-0.3%, P < .001) and 0.20 (95% CI 0.16%-0.24%, P < .001), respectively. This trend also applied to all-cause mortality. CONCLUSIONS: The overall results, including data on specificity, suggest that calcium scores of the coronary and carotid arteries have the most potential for identifying patients with CKD at high cardiovascular risk and for evaluating new therapies.

Non-dipping and higher nocturnal blood pressure are associated with risk of mortality and development of kidney disease in type 1 diabetes.

AIMS: People with type 1 diabetes have increased risk of cardiovascular (CV) and kidney disease. A 24-hour ambulatory blood pressure (BP) measurement (ABPM) examines diurnal variations in BP. We aimed to determine the prognostic significance of blunted decrease in nocturnal systolic BP of <10 % (non-dipping of nocturnal BP) for CV- and kidney disease and all-cause mortality in type 1 diabetes. METHODS: From 2009 to 2011, at Steno Diabetes Center Copenhagen, 654 participants with type 1 diabetes had 24-hour ABPM obtained with a tonometric wrist-watch device (BPro, HealthStats, Singapore). In 2017, outcomes (composite CV endpoint; all-cause mortality; decline in estimated glomerular filtration rate (eGFR) ≥30 %; end-stage kidney disease (ESKD); and a composite kidney endpoint including decline in eGFR ≥30 %, ESKD and all-cause mortality) were registered. Hazard Ratios (HR) were calculated using Cox regressions. RESULTS: Participants were mean ± SD 55 ± 13 years old and had median (IQR) 35 (24-44) years diabetes duration. Mean daytime and nocturnal systolic BP were 133 ± 16 and 121 ± 16 mmHg while 337 (52 %) participants demonstrated non-dipping. After CV risk factor adjustments, non-dipping was associated with all-cause mortality (HR 2.12 (1.09-4.11), p = 0.03) and the composite kidney endpoint (HR 1.92 (1.23-3.00), p = 0.004). CONCLUSIONS: Non-dipping entailed increased risk of all-cause mortality and kidney disease in type 1 diabetes.

Carotid plaque thickness is increased in chronic kidney disease and associated with carotid and coronary calcification.

BACKGROUND: Chronic kidney disease accelerates both atherosclerosis and arterial calcification. The aim of the present study was to explore whether maximal carotid plaque thickness (cPTmax) was increased in patients with chronic kidney disease compared to controls and associated with cardiovascular disease and severity of calcification in the carotid and coronary arteries. METHODS: The study group consisted of 200 patients with chronic kidney disease stage 3 from the Copenhagen Chronic Kidney Disease Cohort and 121 age- and sex-matched controls. cPTmax was assessed by ultrasound and arterial calcification by computed tomography scanning. RESULTS: Carotid plaques were present in 58% of patients (n = 115) compared with 40% of controls (n = 48), p = 0.002. Among participants with plaques, cPTmax (median, interquartile range) was significantly higher in patients compared with controls (1.9 (1.4-2.3) versus 1.5 (1.2-1.8) mm), p = 0.001. Cardiovascular disease was present in 9% of patients without plaques (n = 85), 23% of patients with cPTmax 1.0-1.9 mm (n = 69) and 35% of patients with cPTmax >1.9 mm (n = 46), p = 0.001. Carotid and coronary calcium scores >400 were present in 0% and 4%, respectively, of patients with no carotid plaques, in 19% and 24% of patients with cPTmax 1.0-1.9 mm, and in 48% and 53% of patients with cPTmax >1.9 mm, p<0.001. CONCLUSIONS: This is the first study showing that cPTmax is increased in patients with chronic kidney disease stage 3 compared to controls and closely associated with prevalent cardiovascular disease and severity of calcification in both the carotid and coronary arteries.

Left ventricular remodelling and cardiac chamber sizes in long-term, normoalbuminuric type 1 diabetes patients with and without cardiovascular autonomic neuropathy.

AIMS: Type 1 diabetes is associated with increased cardiovascular (CV) morbidity and mortality, and cardiovascular autonomic neuropathy (CAN) is an important CV risk factor. The study aimed to explore associations between CAN and altered cardiac chamber sizes in persons with type 1 diabetes. METHODS: This was a cross-sectional study of 71 asymptomatic, normoalbuminuric participants with long-term type 1 diabetes (39 with CAN, determined by >1 abnormal autonomic function test) examined with cardiac multi detector computed tomography scans, which allowed measurements of left ventricular mass and all four cardiac chamber volumes. Cardiac chambers were indexed according to body surface area (ml/m2 or g/m2). RESULTS: Persons with and without CAN had mean ±â€¯SD age of 57 ±â€¯7 and 50 ±â€¯8 years (p < 0.001) and diabetes duration of 36 ±â€¯11 and 32 ±â€¯9 years (p < 0.05), respectively. Increasing autonomic dysfunction, evaluated by decrease in heart rate variability during deep breathing (in beats per minute), was associated with larger right (-0.5, 95% CI -1.0 to -0.0, p < 0.05) and trend towards larger left (-0.4, 95% CI -0.8-0.0, p < 0.1) ventricular volumes in multivariable linear regression. CONCLUSIONS: Our results suggest that impaired autonomic function may be associated with modest enlargement of ventricular volumes; this might be an early sign of progression towards heart failure.

Cardiac ventricular sizes are reduced in patients with long-term, normoalbuminuric type 1 diabetes compared to the non-diabetic background population.

AIMS: Type 1 diabetes entails increased cardiovascular morbidity and cardiac chamber sizes are associated with cardiovascular disease. The aim of this study was to compare cardiac chamber sizes in normoalbuminuric persons with type 1 diabetes to a background population without diabetes. METHODS: In a cross-sectional study, we examined 71 normoalbuminuric persons with long-term type 1 diabetes without known cardiovascular disease using cardiac multi-detector computed tomography. Cardiac chamber sizes and left ventricular remodelling were compared to persons without diabetes from the Copenhagen General Population Study. RESULTS: Participants were median (interquartile range) 54 (48-60) (type 1 diabetes) and 57 (50-64) (without diabetes) years old and 59% were men (both groups). Participants with type 1 diabetes had smaller left ventricular mass (-3.5 g/m2, 95% confidence interval -5.8 to -1.3) and left (-4.0 mL/m2, 95% confidence interval -6.9 to -1.0) and right (-11.7 mL/m2, 95% confidence interval -15.4 to -7.9) ventricular volumes in multivariable analyses (adjusted for age, sex, body composition, blood pressure and antihypertensive medication), but no differences in atrial volumes. CONCLUSION: Persons with long-term type 1 diabetes had smaller left ventricular mass and biventricular volumes, yet similar atrial sizes, compared to a background population without diabetes. These findings may reflect subclinical development of diabetic cardiomyopathy.

Possible early detection of coronary artery calcium progression in type 1 diabetes: A case-control study of normoalbuminuric type 1 diabetes patients and matched controls.

AIMS: Coronary artery calcium (CAC) is associated with cardiovascular (CV) disease and progression of CAC is an independent predictor of mortality. Type 1 diabetes is associated with increased CV risk, especially in persons with cardiovascular autonomic neuropathy (CAN). This study aimed to examine whether short-term progression of CAC is increased in persons with type 1 diabetes compared to matched controls and if CAN increases risk of CAC progression. METHODS: Fifty-three normoalbuminuric persons with long-term type 1 diabetes (20 with CAN) were matched in a 1:2 ratio with 106 controls without diabetes according to age, sex and baseline CAC. All were examined twice with cardiac computed tomography scans. Progression of CAC was defined as a value ≥2.5 between the square root-transformed values of follow-up and baseline CAC volume scores. RESULTS: The participants were examined median (interquartile range) of 25 (23-27) months (type 1 diabetes) and 29 (25-33) months (controls) apart. In multivariable logistic regression, participants with type 1 diabetes had an odds ratio of 3.3 (95% CI 1.3-8.2, p = 0.01) for CAC progression. CAN did not increase progression of CAC (p = 0.64). CONCLUSIONS: Progression of CAC was increased in well-treated, normoalbuminuric persons with type 1 diabetes compared to matched controls without diabetes, suggesting that type 1 diabetes is a risk factor for short-term progression. This finding could explain some of the increased morbidity and mortality observed in persons with type 1 diabetes, but it does not specifically explain the increased CV risk in persons with CAN.