Ultrasound-detected tibial artery calcification as a marker of cardiovascular and lower-limb risk in asymptomatic patients with type-2 diabetes.

BACKGROUND: Medial arterial calcification (MAC) is a vascular disease distinct from atherosclerosis. Recently, several studies have demonstrated that MAC is an important marker of cardiovascular events. We aim to assess the presence of MAC during ultrasound screening of lower-limb vasculature and its association with both cardiovascular (CV) and lower-limb events in patients with type-2 diabetes. METHODS: A retrospective cohort study was conducted on 1119 patients with type-2 diabetes free from CV disease. A CV work-up, including vascular ultrasound, was performed for each patient. The presence of MAC was assessed on posterior tibial arteries and ankle-brachial index (ABI) was measured. Major acute CV events (MACEs) and lower-limb events (MALEs) were recorded as a composite endpoint for a 5-year period. RESULTS: We identified MAC among 212 (18.9%) patients. The independent determinants of MAC were age and diabetic retinopathy. Over a period of 5 years, 125 MACEs and 22 MALEs occurred. MAC was significantly associated with the composite outcome MACE + MALE (HR = 1.94; 95% CI: 1.23, 3.08, p = 0.005) or with MACE (HR = 1.85; 95% CI: 1.16, 2.95, p = 0.010). Adjusted for ABI and diabetic foot wound, MAC remained a determinant of MALE (HR = 5.49; 95% CI: 2.19, 13.76, p < 0.001). Considering each ABI group, MAC was associated with both MACE and MALE in the normal ABI group. CONCLUSIONS: Ultrasound-detected MAC on tibial arteries seems to be a determinant of both CV and lower-limb events, independent from ABI. MAC helps to refine the CV risk in patients with normal ABI.

Vascular ultrasound for cardiovascular risk stratification in asymptomatic patients with type-2 diabetes.

AIMS: To identify new independent vascular markers to predict cardiovascular events in patients with type-2 diabetes (T2D), and their incremental value compared to the Swedish National Diabetes Register (NDR) risk score. METHODS: A retrospective cohort study was conducted on 1332 asymptomatic patients with T2D, free from prior CV event, assessed for a cardiovascular work-up, including Duplex ultrasonography to detect plaque on carotid and femoral arteries. The extent of atherosclerosis was rated as atherosclerosis burden score (ABS). Patients were followed up to 5 years and the occurrence of cardiovascular events recorded. RESULTS: A total of 82 patients (6.2%) experienced a cardiovascular event, including 34 (2.6%) myocardial infarction, 18 (1.4%) cardiac revascularisation and 17 (1.3%) stroke. The independent determinants of these events were male sex (HR = 1.81 [1.13-2.88], p = 0.013) and ABS ≥ 2 (HR = 1.98 [1.21-3.25], p = 0.007). The NDR risk score performed poorly to predict cardiovascular events (area under the curve = 0.56 [0.49-0.63], p = 0.11), whereas screening for atherosclerotic plaques provided significant incremental prognostic value over the NDR score (model χ2 increase: +231%, p = 0.002). CONCLUSION: Duplex ultrasonography to screen for atherosclerotic plaques improve the estimation of cardiovascular prognosis on top of clinical data and could be routinely used to improve cardiovascular risk stratification.

A MEN1 syndrome with a paraganglioma.

Germline mutations of the MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterized by tumors of the parathyroids, the pancreas, and the anterior pituitary. Paraganglioma (PGL) is a rare endocrine tumor, which can be sporadic or genetically determined. To date, PGL has never been reported as a feature of MEN1.We report here a patient presenting three features of MEN1 syndrome (hyperparathyroidism, pancreatic neuroendocrine tumor, and adrenocortical adenoma) associated with PGL. Genetic analysis of MEN1 gene revealed a new missense mutation in exon 5 (AGGAAG), causing the substitution of arginine by lysine at codon 275. Screening for other genetic disorders (SDHx, TMEM127, MAX, CDKN1B) causing PGL was negative. Immunohistochemical analyses showed normal levels of succinate dehydrogenase (SDH)A and SDHB in the PGL. The proband's sister, bearing the mutation, had primary hyperparathyroidism. It was the first typical MEN1 syndrome reported with an extra-adrenal PGL.

The prognosis of diabetic patients with high ankle-brachial index depends on the coexistence of occlusive peripheral artery disease.

OBJECTIVES: High ankle-brachial index (ABI) (>1.40) is associated with poor cardiovascular disease (CVD) prognosis. Concomittant peripheral artery disease (PAD) is frequent, although undetectable with the ABI in this situation. We assessed the prognostic value of a high ABI according to the coexistence of occlusive PAD in diabetics. METHODS: In this retrospective longitudinal study, we reviewed the data of 403 consecutive diabetic patients (hospitalized in tertiary care teaching hospital) who had a Doppler assessment of their lower limbs between 1999 and 2000. They were classified as "normal" when Doppler waveform patterns (DWP) were normal and ABI within the 0.91 to 1.39 range, "occlusive-PAD (O-PAD)" when ABI ≤0.90, or in case of abnormal DWP with normal ABI, "isolated medial calcinosis (IMC)" if ABI ≥1.40 with normal DWP, and "mixed disease (MD)" when ABI ≥1.40 with abnormal DWP. The primary outcome was the occurrence of any of the following events: death, stroke or transient ischemic attack (TIA), and acute coronary syndrome. RESULTS: The patients (65.6 ± 13.2 years, 54.6% females) were classified as normal (14.4%), O-PAD (48.4%), IMC (16.4%), and MD (20.8%). During a mean follow-up of 6.5 years, the event-free survival curves of O-PAD and MD groups showed equally poorer prognosis than the IMC and normal groups. Adjusted for age, sex, diabetes type and duration, traditional CVD risk factors, chronic kidney disease, CVD history and treatments, the presence of occlusive disease (hazard ratio [HR]: 2.21, 1.16-4.22, P = .016), but not medial calcinosis, was significantly associated with the primary outcome. CONCLUSIONS: In diabetics with ABI >1.40, only those with concommittant occlusive PAD have poorer prognosis.