Objectives: To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and individually. Methods: In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results: Of the 200 randomized patients, 165 for per-protocol and 160 for the safety (QTc intervals) were set, respectively. Probucol significantly reduced total cholesterol (P <0.001), low-density lipoprotein cholesterol (LDL-C), (P = 0.01), and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) compared with conventional therapy. Cilostazol was effective in increasing HDL-C (P = 0.002) and reducing triglycerides levels (P < 0.01) compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein (Ox-LDL, P = 0.065). No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions: We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies. ©2012 JGC All rights reserved.

Serum concentration of apolipoprotein B (Apo B) is causally associated with arteriosclerosis cardiovascular disease (ASCVD) risk. Whether ATP-sensitive potassium channels (KATP) variants predict the risk of increased Apo B concentration (≥ 80 mg/dL) and related ASCVD remain less clear. We recruited 522 subjects with elevated Apo B concentration (≥ 80 mg/dL) and 522 counterpart subjects (< 80 mg/dL) from South China to assess the associations of KATP variants (rs11046182, rs78148713, rs145456027 and rs147265929) with the risks of increased Apo B serum concentration (≥ 80 mg/dL), carotid artery stenosis (CAS) ≥ 50% and new-onset ischemic stroke (IS). Our results showed that only KATP SNP rs11046182 (GG genotype) was associated with increased risk of Apo B ≥ 80 mg/dL (adjusted OR=2.17, P<0.001) and CAS ≥ 50% (adjusted OR=2.63, P=0.011). After median 50.6-months follow-up, subjects carrying GG genotype of rs11046182 were associated with higher risk of new-onset IS (adjusted HR=2.24, P=0.024). Further, the exosome-derived microRNAs (exo-miRs) expression profile was identified by next-generation sequencing. 41 exo-miRs were significantly differentially expressed under cross-talk status between high Apo B level (≥ 80 mg/dL) and KATP rs11046182. Our study demonstrated that KATP variant rs11046182 was associated with higher risks of elevated serum Apo B levels and its related ASCVD, and the possible mechanism was related to specific exo-miRs expression profile of KATP rs11046182.

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BACKGROUND:

Surgery is a well-known trigger of keloid and hypertrophic scarring. Sternotomy scars are subject to high skin tension, which is known to promote pathologic scarring. This suggests that sternotomies in adults are associated with high pathologic scarring rates, which aligns with the authors' anecdotal experience. However, this notion has never been examined formally. Therefore, the authors conducted a survey-based cohort study of patients who had undergone a sternotomy.

METHODS:

All consecutive Japanese adults (18 years of age or older) who underwent cardiovascular surgery with sternotomy in 2014 to 2017 were identified in 2019 by chart review and sent a questionnaire. Respondents formed the study cohort. The questionnaire presented randomly ordered photographs of representative mature, keloid, and hypertrophic scars and asked the patients to choose the image that best resembled their midline scar when it was particularly noticeable. The incidence of self-reported pathologic scarring (keloids and hypertrophic scars were grouped together) and the patient demographic (age and sex) and clinical characteristics (intima-media thickness of the left and right common and internal carotid arteries) that were associated with pathologic scarring were determined.

RESULTS:

Of the 548 patients who underwent sternotomy, 328 responded for a 60 percent response rate. The mean patient age was 67 years, and 68.0 percent were male. Of these patients, 195 (59.5 percent) reported they had a pathologic scar. Compared with patients who had a mature scar, patients who had a pathologic scar had younger mean age (65 versus 69 years; p = 0.0002) and lower intima-media thickness (0.92 versus 1.05 mm; p = 0.028).

CONCLUSIONS:

Sternotomy was associated with a high rate of pathologic scarring. Older age and arteriosclerosis were associated with less pathologic scarring.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.

INTERVENTION:

Observation of changes with a cilnidipine administration. Observation of changes with a amlodipine administration.

CONDITION:

Diabetes/Hypertension/Sleep apnea syndrome

PRIMARY OUTCOME:

office blood presure; PWV; IMT; urinary albumin (diabetes only); urinary LFAB‐

P SECONDARY OUTCOME:

e‐GFR ; adiponectin; hs‐

CRP INCLUSION CRITERIA:

1) Hypertensive patients not reaching the step‐down goal, even the administration of RAS inhibitors for more than three months or no medication. 2) Diabetic nephropathy 3) Patients complicated with sleep apnea syndrome. Among the above‐mentioned; 1)+2)+3) or 1)+2) or 1)+3)

Background: A selective 5-HT2 receptor antagonist, sarpogrelate, has been known to improve clinical symptoms in patients with arteriosclerosis obliterans (ASO). Many physicians have conducted in vitro studies to elucidate the mechanism involved in this effect and established that sarpogrelate inhibits platelet aggregation and proliferation of the vascular smooth muscle cells (VSMC). Methods: A total of 50 patients (30 older men and 20 postmenopausal women), all with a history of intermittent claudication and given a diagnosis of ASO, served as the subjects of this study. Sarpogrelate (200-300 mg/day) was prescribed for about 30 months. They were grouped by Fontaine classification (0-3). The intimal-medial thickness (IMT) of their carotid artery and cardiac function were measured and analyzed by ultrasonography and ultracardiosonography. The results of blood chemical analysis, blood pressure, and heart rate were analyzed at intervals of 3 or 6 months (starting at 0, then on the 3rd, 6th, 9th, 12th, 18th, 24th, and 30th month). Pulse wave velosity (PWV) was measured only for the last two years because no devices were available prior to that. The co-morbidity of these patients included: hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular disease, chronic renal failure, chronic glomerulonephritis, nephrotic syndrome, hyperlipidemia, and congestive heart failure. For these conditions, appropriate medication was prescribed in addition to sarpogrelate. Results: The IMT gradually decreased in most of the patients within the 30-month period (p < 0.0001). Sarpogrelate also improved PWV, ankle brachial pressure index (ABI), and cardiac functions (p < 0.0001) in spite of the complications cited above. The medication also enabled the patients with intermittent claudication to walk further distances and for a longer duration without pain in their lower extremities. This finding indicated that sarpogrelate exerts a direct effect to attenuate and inhibit both the progression and exacerbation of atherosclerosis (including arteriosclerosis). None of the patients experienced side effects from sarpogrelate during the trial. Conclusion: In the present study involving patients with ASO, sarpogrelate markedly improved the conditions of intermittent claudication, with increases in ABI and decreases in IMT and PWV, especially in those with diabetes mellitus.

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Background: Recently published genetic studies have indicated a causal link between elevated insulin levels and cardiovascular disease (CVD) risk. We, therefore, hypothesized that increased fasting insulin levels are also associated with precursors of CVD such as endothelial lesions. Methods: Middle-aged (≥40 years, n = 1,639) employees were followed up for the occurrence of increased intima media thickness (IMT ≥ 1 mm) or plaques in abdominal or cervical arteries (arteriosclerosis). Multivariable logistic regression analyses determined the incidence of increased IMT or arteriosclerosis. Adjusted relative risk (ARR) for increased IMT and arteriosclerosis was calculated by using Mantel-Haenszel analysis. Results: Increased IMT was diagnosed in 238 participants (15 %) and 328 (20 %) developed arteriosclerosis after 5 years of follow-up. Logistic regression analysis identified fasting insulin, BMI and smoking as risk factors for both cardiovascular endpoints (all p < 0.05), whereas age and diastolic blood pressure were risk factors for increased IMT only, and male sex was associated with incident arteriosclerosis only (all p < 0.01). Additional adjustment for BMI change during follow-up did not modify these associations (including fasting insulin), but adjustment for fasting insulin change during follow-up removed BMI as risk factor for both cardiovascular endpoints. Fasting insulin change during follow-up but not BMI change associated with increased IMT and arteriosclerosis (both p < 0.001). ARR analysis indicated that high fasting insulin and BMI added to age and sex as risk factors. Homeostatic model assessment of insulin resistance (HOMA-IR) did not associate with either cardiovascular endpoint in any model and smoking did not increase the risk conferred by high fasting insulin levels. Conclusions: Higher fasting insulin levels and increases in fasting insulin over time are associated with atherogenic progression and supersede BMI as well as HOMA-IR as risk factors.

INTERVENTION:

Trade Name: Actos 45 mg Product Name: Pioglitazon Pharmaceutical Form: Tablet Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Actos 30 mg Product Name: Pioglitazon Pharmaceutical Form: Tablet Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use

CONDITION:

Male or female non‐diabetic patients at an age between 30 and 79 years (inclusive) with a proven vascular disease defined as arteriosclerosis confirmed by presence of CAD, PAD or carotid plaques.

PRIMARY OUTCOME:

Main Objective: Exploration of possible differences in the effect on IMT (as the total vessel wall volume in MRI) of an add‐on‐therapy with pioglitazone versus placebo in non‐diabetic patients with confirmed arteriosclerosis in order to gain more detailed information and to generate valid hypotheses for further project planning. Primary end point(s): Analysis of the total vessel wall volume of the carotid bulbus/bifurcation (CB) determined with MRI after 24 months of study treatment compared to baseline (Visit 2; Day 1) Secondary Objective: Evaluation of relevant further efficacy, safety and tolerability parameters considering IMT‐measurements, MR‐angiography (patient subgroup), laboratory variables, vital signs and adverse events in non‐diabetic patients with confirmed arteriosclerosis under add‐on‐therapy with pioglitazone compared to placebo. ; In a selected subgroup of study patients defined as patients with proven significant (>50% stenosis) proximal coronary artery disease without ischemia (no invasive treatment with PTCA or stenting), a visualization of the coronary vessel status (MRI assessment of the vessel lumen and the vessel wall thickness) will be performed additionally by specific MR‐angiography.

INCLUSION CRITERIA:

Male or female patient at an age between 30 and 79 years (inclusive); the patient has a proven vascular disease defined as arteriosclerosis confirmed by the presence of CAD or PAD or carotid plaques; normal HbA1c (< 6%) plus normal fasting blood glucose (< 126 mg/dl) for 2 days prior to randomization (according to pre‐study routine laboratory investigations); negative pregnancy test on Study Day 0 (Visit 1) in women with childbearing potential; signed and dated written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range