Heart-Rate Reduction With Adjusted-Dose Ivabradine in Patients Undergoing Coronary Computed Tomographic Angiography: A Randomized Trial.

OBJECTIVE: Our prospective, randomized, open-label study assessed the efficacy of a heart rate-lowering, adjusted-dose protocol with ivabradine prior to coronary computed tomographic angiography (CCTA). METHODS: Patients undergoing CCTA were randomized to 7 days of adjusted-dose ivabradine or standard care (ie, no additional medication). Heart rate and ß-blocker and antianxiety medication use on the day of the CCTA were recorded. RESULTS: One hundred one patients were randomized (mean age, 60 [SD, 13] years; 66% women). Significantly more patients on ivabradine had heart rates of 60 beats per minute or less at the time of the CCTA scan (48% vs 8%, P < 0.01); accordingly, fewer patients on ivabradine needed additional heart rate lowering with ß-blockers (40% vs 86%, P < 0.01), as well as antianxiety medication (18% vs 39%, P < 0.05), and also required lower doses of intravenous ß-blockers (4 [SD, 2] vs 7 [SD, 5] mg, P < 0.05). CONCLUSIONS: A 7-day premedication protocol with ivabradine effectively lowers heart rate in patients undergoing CCTA.

Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. PATIENTS AND METHODS: 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. RESULTS: No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], ß- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p < 0.01]. CONCLUSIONS: No significant differences between groups were found in carotid artery morphology and function, digital endothelial function or overall coronary calcium score. Significantly more ET patients had an elevated coronary calcium score of >160, indicating high cardiovascular risk, not predicted by the Framingham equation.

Progression of coronary calcium burden and carotid stiffness in patients with essential thrombocythemia associated with JAK2 V617F mutation.

BACKGROUND AND AIMS: Patients with myeloproliferative neoplasms often succumb to cardiovascular events, but little is known on the early stages of their vascular disease. We studied how patients with JAK2 V617F positive essential thrombocythemia (ET) without overt atherosclerotic disease differed from control subjects in the progression of carotid artery stiffness and preclinical atherosclerosis. METHODS: Thirty-six patients with JAK2 V617F positive ET and 38 age-, gender- and Framingham coronary heart disease (CHD) -matched control subjects were examined twice within 4 years. Clinical and laboratory testing, echo-tracking ultrasound of carotid arteries, coronary calcium measurement and digital plethysmography were performed (ClinTrials.gov NCT03828422). RESULTS: Coronary calcium correlated with the Framingham CHD risk score at the first examination in the control group (rs = 0.410), but not among the ET patients (rs = 0.116). Both groups progressed in coronary calcium, but the outliers were more prominent among ET patients. Carotid artery stiffness increased with time in the ET patients much more than in the control group: the increase in ß-index 1.95 (SD 2.18) vs. 0.22 (SD 1.99), p < 0.001, and the increase in carotid pulse wave velocity 0.72 (SD 0.92) vs. 0.08 (SD 0.72) m/s, p = 0.001. There was no correlation between carotid stiffness and Framingham CHD risk in either group. Digital endothelial function did not change. CONCLUSION: Carotid artery stiffness progressed faster in patients with JAK2 V617F positive ET than in control subjects. Coronary calcium correlated with the Framingham CHD risk only in control subjects. This indicates that JAK2 V617F positive ET acted as a non-classical risk factor for vascular disease.

Longitudinal hair chromium profiles of elderly subjects with normal glucose tolerance and type 2 diabetes mellitus.

Longitudinal hair chromium (H-Cr) profiles in a group of patients with type 2 diabetes mellitus (n = 59; age, 62 +/- 9 years) and healthy elderly (control) subjects (n = 49; age, 59 +/- 10 years) matched by age and sex were measured by solid sampling electrothermal atomic absorption spectrometry, providing data on the magnitude of variation of Cr content along the hair length. H-Cr average (H-Cr(av)) and H-Cr proximal (H-Cr(pr))(.), relating to the average Cr content of the whole hair and the proximal 3-mm hair length, respectively, were also obtained. No significant difference between the healthy and diabetic group was found in mean H-Cr(av) or H-Cr(pr) contents (248 +/- 108 vs 247 +/- 143 and 233 +/- 98 vs 278 +/- 195 ng/g, respectively. However, women in the control group had significantly lower H-Cr values (P < .01) compared with men, but this difference was absent in the diabetic population. The distribution of log H-Cr(pr) values in the control population displayed a Gaussian shape, in contrast to the substantially wider distribution, skewed toward lower H-Cr(pr) values, observed in the diabetic group. The magnitude of variation in H-Cr content in the patient group over an interval of approximately 2 to 3 months (time of growth of the hair sampled) was found to be a factor of more than 2 larger than that in the control population (+/- 58% vs +/- 26%). A strong relationship (R = 0.656; P < .01) between log H-Cr(pr) and log fasting plasma Cr was observed in the diabetic group (n = 20). The mean fasting plasma Cr value of this group was 0.41 +/- 0.10 microg Cr per liter. No correlation between H-Cr(av.) and duration of diabetes was observed. A strong positive association was observed in the control population between H-Cr(pr) and fasting plasma insulin (n = 22; R = 0.6157; P < .01), and H-Cr(pr) and fasting plasma glucose (n = 24; R = 0.4118; P < .05), which is indicative of the interrelation of these parameters. In the control population, H-Cr(av) showed a slight decrease with age (n = 54; R = 0.2691; P < .05), which is assumed to be the result of increased insulin resistance caused by various age-associated factors including Cr deficiency. None of the above relationships was significant in the diabetic group. Evidence is presented that justifies the assumption that the longitudinal H-Cr profile resembles the variation in Cr metabolic rate over the time span of growing hair, which is not appreciably affected by external contamination. This suggests that glucose intolerance (type 2 diabetes mellitus) is an important factor that disturbs Cr metabolism.

Chromium supplementation shortens QTc interval duration in patients with type 2 diabetes mellitus.

BACKGROUND: We investigated the potential effects of chromium supplementation on QTc interval duration in type 2 diabetic patients. METHODS: Of 60 patients with type 2 diabetes mellitus, 30 were randomly assigned to group A, and 30 to group B. Group A received 1000 microg of chromium picolinate (CrPic) daily for 3 months, followed by placebo in the next 3 months; group B was treated with placebo for the first 3 months and CrPic in the next 3 months. At each visit, QT interval was measured on a standard electrocardiogram by averaging 3 consecutive beats in leads II and V4 and corrected for heart rate with Bazett formula. RESULTS: Although baseline QTc interval was similar in both groups (422 +/- 34 milliseconds in group A vs 425 +/- 24 milliseconds in group B, P = .77), QTc interval at 3 months was shorter in group A (406 +/- 35 milliseconds) than in group B (431 +/- 26 milliseconds, P = .01). In the following 3 months, QTc interval shortened in group B but not in group A, which resulted in a comparable QTc interval duration of both groups at the end of the study (414 +/- 28 milliseconds in group A vs 409 +/- 22 milliseconds in group B, P = .50). Apart from body mass index (31.4 +/- 4.2 kg/m2 in patients with QTc shortening vs 28.7 +/- 4.2 kg/m2 in patients without QTc shortening, P = .03), none of the clinical and laboratory variables predicted QTc interval shortening in our patient cohort. CONCLUSIONS: Short-term chromium supplementation shortens QTc interval in patients with type 2 diabetes mellitus.

Haemodialysis clearance of baclofen.

BACKGROUND: Baclofen is a centrally acting gamma-aminobutyric acid agonist used for spasticity of spinal origin and mainly excreted unchanged by the kidneys. We report haemodialysis clearance and the haemodialysis removal rate constant of baclofen in a comatose patient with baclofen overdose due to acute renal failure. CASE REPORT: A 60-year-old man with spastic tetraplegia on chronic baclofen therapy was admitted due to pneumonia and acute renal failure. The patient became comatose and, as a result of the baclofen dosage being left unchanged despite a deterioration leading to renal failure due to hypotension, the concentration of baclofen was determined to be in the toxic range (0.70 mg/L). During a 4-hour-long bicarbonate haemodialysis the patient woke up and became completely orientated and cooperative. Baclofen therapy was subsequently stopped, and the patient remained conscious. The pharmacokinetics calculations revealed a baclofen haemodialysis removal rate constant of 0.152 h(-1) and a haemodialysis clearance of 2.14 mL/s. CONCLUSIONS: Patients on a stable baclofen regime can develop baclofen toxicity due to acute renal failure. Haemodialysis removes baclofen as effectively as normal kidneys, and it would appear that haemodialysis is a reasonable treatment modality in patients with accidental baclofen overdose due to acute renal failure.

The impact of the timing of Humalog Mix25 injections on blood glucose fluctuations in the postprandial period in elderly patients with type 2 diabetes.

BACKGROUND: Postprandial hyperglycemia contributes to glycation of hemoglobin A1c and has been associated with cardiovascular risk in people with diabetes. We investigated the impact of injection timing of Humalog Mix25 (Mix25, known as Humalog Mix75/25 in the U.S.: 25% insulin lispro and 75% neutral protamine lispro) on glycemia and postprandial blood glucose (BG) excursions in elderly individuals MATERIAL/METHODS: Seventy-three patients aged 60 to 80 years were randomized to Mix25 (Mix25 group, 37 participants) or a continuation with maximum dose glibenclamide (control group, 36 participants). The Mix25 group was subdivided into a group of 18 patients who were injecting insulin after meals and 19 who were injecting before. RESULTS: At baseline, the absolute postprandial BG concentrations and postprandial BG excursions after breakfast were high (Mix25 group: 15.3+/-4.8 mmol/l and 3.5+/-2.7 mmol/l, respectively; controls: 15.4+/-3.9 mmol/l and 4.7+/-2.7 mmol/l, respectively). In both groups improvement was observed at the endpoint, but it was greater with Mix25 (Mix25 group: 10.3+/-3.6 mmol/l, p<0.0001 vs. baseline, p<0.003 vs. controls, and 2.0+/-2.5 mmol/l, p<0.008 vs. baseline, p=ns vs. controls; control group: 13.3+/-2.9 mmol/l, p<0.006 vs. baseline, and 4.7+/-2.7 mmol/l, p<0.006 vs. baseline). The two Mix25 subgroups had similar postprandial BG levels and BG excursions after breakfast. CONCLUSIONS: Mix25 improves postprandial BG and yields a greater effect on BG excursions compared with monotherapy with glibenclamide. The timing of Mix25 did not impact the level of BG or BG fluctuations after meals, which may be important for individuals with changing dietary pattern.