Vascular Disease Prevention (Discontinued) - Volume 5, Issue 2, 2008

Background: The association between body mass index (BMI) and the development of type 2 diabetes (T2DM) is well established. The determinants of the resolution of T2DM with weight reduction after bariatric surgery, however, are not fully understood. Objective: Examine the course of T2DM during weight loss after bariatric surgery. Methods: Through a retrospective chart review, 56 morbidly obese, diabetic patients who underwent bariatric surgery were followed for 12 months. Resolution of T2DM was defined as an initial elevated glycohemoglobin (HbA1C) > 6.0% that decreased to < 6.0% with weight loss allowing discontinuation of all diabetic medication. Results: Of the 56 with T2DM, 31 (55.4%) resolved T2DM. The mean age ± SD was 49.0 ± 7.3 and 53.1 ± 7.0 years for resolved and persistent T2DM, respectively (p = 0.04). The baseline BMI was higher in the resolved group, measuring, 51.3 ± 8.3 kg/m2 compared with the persisted group of 46.5 ± 4.9 kg/m2, p = 0.02. The final BMI was 33.6 ± 7.6 kg/m2 and 33.9 ± 5.2 kg/m2, p = 0.87 for the resolved and persistent cases, respectively. The absolute and relative reductions in BMI were -17.6 ± 3.6 kg/m2 and -12.6 ± 6.3 kg/m2, p < 0.0001; and -34.7 ± 6.3% and -26.6 ± 11.9%, p = 0.002, over a mean duration of 12.9 ± 1.4 and 10.8 ± 5.2 months for resolved and persistent cases, respectively. Multiple logistic regression found factors such as a higher baseline BMI, p = 0.006, and lower final BMI, p = 0.03, were independent predictors of the resolution of T2DM while lower baseline HbA1C, p = 0.09, approached significance. There was a spike in HbA1C at 6 weeks in those with resolution of T2DM while there was a curvilinear decline in HbA1C in persistent T2DM with failure to normalize. Conclusions: Resolution of T2DM after bariatric surgery is a dynamic process and is associated with substantial weight loss and good glycemic control during the pre- and post-operative periods beyond 6 weeks.

Fibrin-related markers, such as fibrin and fibrinogen degradation products (FDP) and D-dimer, are considered useful for the diagnosis of thrombosis. However, the evidence for making a diagnosis of thrombosis based on fibrinrelated markers is still not yet well established. The plasma concentrations of soluble fibrin and D-dimer were prospectively measured in 680 inpatients suspected of having thrombosis between October 1, 2003 and January 31, 2005, and correlated with thrombosis. The normal ranges of D-dimer and FDP were within 0.76 μg/ml and 1.50 μg/ml, respectively. Out of 680 patients, 129 patients showed plasma concentrations associated with thrombosis, including 73 with deep venous thrombosis (DVT)/ pulmonary embolism (PE). The plasma D-dimer and FDP concentrations were significantly higher in the patients with thrombosis than in the patients without thrombosis, but there were no significant differences in the D-dimer and FDP levels among the patients with thrombosis. The plasma D-dimer levels were significantly correlated with the plasma FDP levels in all the patients and there was no significant difference in the ratio of FDP/ D-dimer among the various diseases. A ROC analysis showed that both FDP and D-dimer were useful for the diagnosis of all types of thrombosis and DVT. The cutoff values of D-dimer (3.8 μg/ml) and FDP (7.7 μg/ml) had high sensitivity, specificity and negative predictive values (NPV) but low positive predictive value. Our findings suggest that FDP showed a close correlation with D-dimer, which is known to be a marker for a hypercoagulable state, and it is also reflects a high risk for thrombosis.

Inflammation is a key process linked to stroke both in terms of atherosclerosis, and in terms of cerebral ischaemia. Secondary to endothelial injury, innate and acquired immune mechanisms maintain a chronic low-grade inflammatory state, which initially contributes to formation of atherosclerotic plaques, and ultimately leads to detrimental complications, such as rupture and thrombosis. Experimental models of cerebral ischaemia have shown that inflammatory immune cascades mediate ischaemia/reperfusion injury, and therefore, could be strongly related to stroke outcome. In the case of atherosclerosis and ischaemic stroke, the pro-inflammatory (Type-1) cytokines predominate over their counterparts, the anti-inflammatory (Type-2) cytokines. Elevated plasma levels of Type-1 cytokines have been associated with unstable atherosclerotic plaques and risk of stroke, while Type-2 cytokines seem to relate with better functional outcome after stroke. Multiple genetic variations (e.g. single nucleotide polymorphisms) have been identified in the genes of these molecules, some of which seem to regulate their transcription rate, or their functionality. The association of these genetic variants with risk of stroke and post-stroke functional outcome has been extensively investigated. We systematically review polymorphisms of inflammatory cytokines associated with ischaemic stroke, in respect to their immune type (Type-1 or 2), and provide possible implications for stroke prevention, therapy and future research.

Calcium is integral to cardiac excitation and contraction. The main route for calcium influx into cardiac myocytes is the L-type Ca2+ channel. Once intracellular calcium levels are increased, a number of calcium-dependent signal pathways are activated that can lead to persistent changes in protein synthesis and function. This process is termed “pathological remodeling”. Pathological remodeling of the heart can progress to irreversible changes in heart size and function that ultimately results in heart failure and death. It is well recognized that calcium-dependent pathways contribute to the process of pathological remodeling but reactive oxygen species have also emerged as an important participant in cardiac pathology. The early mechanisms that trigger remodeling have been poorly understood. Recent evidence links calcium influx through the L-type Ca2+ channel with persistent changes in cellular calcium and cellular redox state as a possible early mediator of pathological remodeling.

Atherosclerosis is the most common cause of death in the Western population. Apoptosis has now been recognized as a major event in a number of common and threatening vascular diseases, including in the pathophysiology of atherosclerosis. Consistent with an increasing body of evidence from both, animal models and human specimens, modified low-density lipoprotein-induced apoptosis of vessel wall cells contributes to the development and progression of this disease. Because apoptosis is a highly regulated process and represents the predominant mechanism of cell death in atherosclerosis, its investigation is receiving increasing attention to clarify the underlying molecular mechanisms which will help to design novel specific therapeutic strategies to reduce disease progression. However, since the major cell types involved are blood cells like macrophages (MΦ) and lymphocytes, but also endothelial and smooth muscle cells (Fig. 1), the significance of apoptosis and its relevance in atherosclerosis is likely to be associated with the cell type affected. In this context biochemical, immunocytochemical, functional genomics and genetic analyses provide an increasingly detailed picture of the intracellular signaling pathways being involved in each cell type. For example, extrinsic or intrinsic deathsignaling pathways appear to be activated in blood cells or cells in atherosclerotic lesions and to mediate vascular apoptosis during atherogenesis. We aim to provide a timely overview of apoptogenic signaling pathways in different cell types of the vessel wall, to discuss the relevance of apoptosis in the various cell types and links to inflammation, but also to summarize emerging therapeutic pro-/anti-apoptotic options.

Objective. Evaluate the effect of a multidisciplinary behavioral childhood/adolescent obesity treatment program on body mass index (BMI). Methods. Height and weight were measured and BMI was calculated at start and completion of a 12-session program in 74 consecutive children/adolescents. Results. Mean age was 12.2 ± 3.2 years and mean baseline BMI z score was 2.4 ± 0.3, corresponding to a BMI percentile of 98.9 ± 1.0%. The majority, 57% (n=42), completed all 12 sessions. Those completing all sessions were younger (11.6 vs. 13.2 years old, p<0.04) and had a lower baseline BMI z score (2.3 vs. 2.5, p=0.01). Twenty-two (52%) had a significant decrease in BMI z score (p<0.001), with a mean decrease of 13.8%. Conclusions. Lower attrition for a childhood/adolescent obesity treatment program was associated with younger age and lower baseline BMI z score. Over half of participants that completed an educational multidisciplinary obesity treatment program experienced a decrease in BMI z score, independent of their gender.

Disturbances in homocysteine metabolism may lead to hyperhomocysteinemia. This condition has been associated with vascular atheromatosis leading to coronary artery disease (CAD) as well as myocardial infarction. One hundred patients with CAD who underwent coronary artery bypass grafting (CABG) were enrolled. The study aimed to evaluate cardiac enzymes and electrocardiogram of each patient postoperatively so as to diagnose perioperative myocardial infarction (PMI). An initial decrease of homocysteine immediately postoperatively followed by a progressive increase was recorded. Mild hyperhomocysteinemia preoperatively was more frequent among the patients who developed PMI. A correlation of preoperative homocysteine with troponin in the PMI group was also noted. Homocysteine levels were a prognostic factor for the occurrence of PMI in CABG procedures.

Transforming growth factor-β1 (TGF-β1) is known to have a contradictory role in the pathogenesis of atherosclerosis. We assessed the relationship between TGF-β1, age and ultrasound parameters of the arterial wall in subjects with coronary artery disease (CAD) and a control group (C group). In both groups age was significantly related to the diameter of brachial artery (BA), diameter of common carotid artery (CCA) and intima-media thickness (IMT) of the near and far CCA wall. A correlation between TGF-β1 and age was not found. In C group, relationships between TGF-β1 and the diameter of BA at rest (r = - 0.47, p = 0.007), in the 60th sec (r = - 0.44, p = 0.01) and in the 90th sec of reactive hyperemia (r = - 0.45, p = 0.01) were observed. Similarly, TGF-β1 was related to CCA diameter (r = 0.56, p = 0.002). The correlations between TGF-β1 and CCA IMT of the near wall (r = 0.62, p = 0.007) and far wall (r = 0.55, p = 0.02) were seen in the C group. We suggest that these relationships reflect arterial remodeling.

Hypertension related decrements in cognitive functioning have been documented in those without clinical evidence of vascular disease and in individuals unaware of their hypertension. Impaired cognition in asymptomatic hypertensives may or may not be altered by antihypertensive therapy. We have examined the effect of three months of ramipril therapy on ambulatory blood pressure, cognitive function, lipid peroxidation and nitric oxide levels. Thirty male asymptomatic, newly diagnosed hypertensives were administered ramipril 5mg daily orally. Ambulatory blood pressure was recorded before and after three months of therapy. Cognitive function was assessed using event related potentials (N2 and P300 waveforms). Malondialdehyde was used as a marker of lipid peroxidation and serum nitrite levels were used as an index of nitric oxide levels. Along with the antihypertensive effect, three months of ramipril therapy improved the P300 but not the N2 latency. There was a positive correlation between the P300 latency and the systolic blood pressure parameters of the ambulatory blood pressure. The serum nitrite levels were increased and the malondialdehyde levels were decreased after therapy. Thus ramipril may improve some aspects of cognitive function by affecting the serum nitrite and lipid peroxidation pathways.