Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of cross-sectional studies addressing early preintrusive atherosclerosis in type 1 diabetic patients are conflicting. In an observational longitudinal study we determined the course of carotid artery intima-media thickness (IMT) over a period of 2.5 years in mean. A total of 102 patients with type 1 diabetes mellitus (age < or = 40 years, diabetes duration > or = 2 years at baseline examination) who were participants of the baseline examination was studied again in a follow-up. HbA1c, albumin excretion rate (AER), lipids, systolic and diastolic blood pressure, retinopathy, and current smoking status were assessed at baseline and follow-up. The IMT of the common carotid artery was measured by high-resolution ultrasound, the maximum IMT was evaluated. The annual progression rate (APR) was calculated from the difference between baseline and follow-up IMT reading and the time between both examinations. The follow-up IMT was significantly higher, compared to the baseline measurement: 0.65 +/- 0.18 vs. 0.57 +/- 0.14 mm (p < 0.001), the mean APR was 0.033 mm/year. The APR was correlated with age (r = 0.337, p < 0.01), diabetes duration (r = 0.252, p < 0.05), hypertension (r = 0.225, p < 0.05), and systolic blood pressure (r = 0.281, p < 0.05) at the baseline examination. Comparing subgroups, defined according to APR tertiles, with no IMT progression (first tertile, mean APR - 0.012 mm/year), mild progression (second tertile, mean APR 0.037 mm/year), and advanced progression (third tertile, mean APR 0.088 mm/year), patients with advanced progression significantly (p < 0.05) more often had hypertension and nephropathy than subjects with mild progression. In a multiple linear regression analysis, the changes of plaque frequency and of the nephropathy status between baseline and follow-up examinations were independent predictors of the APR.
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PMID:Determinants of early carotid atherosclerosis progression in young patients with type 1 diabetes mellitus. 1192 73

BACKGROUND: Macrovascular disease in diabetes mellitus is a multifactorial process resulting in part from accelerated atherosclerosis and increased thrombosis. The resultant cardiovascular mortality is up to five times that of an age-matched non-diabetic population. Recently, cell adhesion molecules (CAMs) have been demonstrated in atherosclerotic plaques and implicated in the initiation and development of atherosclerosis. METHODS: To assess circulating CAMs as potential predictors of the development of macrovascular disease in diabetes mellitus, we carried out a 5-year prospective study in 28 diabetic patients without manifest macrovascular disease at entry. Circulating CAMs [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin and E-selectin] were measured at baseline and at follow-up. RESULTS: Except for neuropathy, no patient had other microvascular diabetic complications (retinopathy or nephropathy) or clinically manifest macrovascular disease. Eleven patients developed macrovascular disease at follow-up (seven coronary heart disease, two cerebrovascular disease, two peripheral vascular disease). At baseline, systolic blood pressure and serum creatinine were higher (but within normal range) in patients developing macrovascular disease. Baseline ICAM-1 was significantly higher in the patients who developed macrovascular disease than in those who did not, and it remained so even after adjusting for age, systolic blood pressure, creatinine and glycaemic control (P=0.0007). However, baseline VCAM-1, P-selectin and E-selectin were not found to be associated with macrovascular disease. The risk of developing macrovascular disease was associated with increasing baseline concentrations of ICAM-1 [odds ratios 1.04 (95% CI 1.01-1.07); P=0.01]. No correlation was seen between ICAM-1, HbA(1) and cholesterol. CONCLUSION: This study suggests that ICAM-1 may predict development of macrovascular disease in diabetes mellitus.
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PMID:Circulating cellular adhesion molecules ICAM-1, VCAM-1, P- and E-selectin in the prediction of cardiovascular disease in diabetes mellitus. 1202 Jun 26

Many types of adverse ocular reactions to oral contraceptives (OCs) have been reported, but the role of OCs has not always been confirmed. Neuroophthalmologic complications may result from cerebral vascular accidents responsible for visual field deficits, accidents affecting the cerebral trunk, ischemic accidents resulting from obstruction of the internal carotid artery. The role of OCs in cerebral vascular accidents is controversial. Most reports concern older formulations containing high doses of estrogen. In the current state of knowledge it is generally agreed that OCs may induce an increased thromboembolic risk in women over 35, those who smoke, and those with risk factors for atherosclerosis. It is agreed that occurrence of a transient ischemic cerebral vascular accident requires immediate termination of OC use. OCs have been implicated occasionally in retrobulbar optic neuropathy, but the condition in young women appears more likely to be the 1st manifestation of a sclerosis. OCs appear to increase the incidence of benign intracranial hypertension, manifested by headaches, papillary edema endangering the optic nerve, and the absence of visible anomalies on the scanner. It is also recognized that migraines are induced or aggravated by OCs. Migraines are known to be linked to hormonal factors. Ophthalmic migraines belong to the subgroup of vascular migraines. Retinal vascular diseases such as occlusion of the central retinal artery, intraocular hemorrhage, and more rarely macular edema have been reported retrospectively but their documentation has been insufficient to permit determination of causality. The prognosis for retinal emboli is mediocre. Problems in color vision initially affecting blue have been described in OC users and may be a function of the duration of use. The condition is especially prevalent in diabetes. Pregnancy appears to accelerate the loss of visual field in some women with pigmentary retinopathy. For that reason some ophthalmologists recommend that they avoid OCs. Other ocular problems have been observed in OC users but no link has been proven and the only evidence is anecdotal. It has been suggested that OCs decrease tolerance for contact lenses, but prospective studies have not demonstrated a link. All contraindications to OC use should be scrupulously respected. Use should be terminated immediately in case of transient ischemic accident, appearance of sudden severe headaches, vertigo, or vision problems such as papillary edema or retinal hemorrhage.
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PMID:[Adverse ocular reactions to oral contraceptive use]. 1231 84

Coronary insufficiency affects 55% of insulin-dependant diabetics and is responsible for 60% of deaths in this population. Its particular severity is essentially due to the severity of coronary atherosclerosis, which is usually multi-vessel, involves both large trunks and microcirculation, is made of frequently lipid-rich and therefore fragile plaques, and is accompanied by abnormal but specific reactions of the arterial wall (tendency to vasoconstriction and increased neointimal proliferation after trauma). Coronary atherosclerosis is also often associated with HT, lower limb arteriopathy or cerebral atherosclerosis. Quality of blood glucose control, other organic lesions of diabetes (nephropathy, retinopathy), disturbances of platelet function and dyslipidaemias (hypercholesterolaemia, hypertriglyceridaemia, increased levels of highly atherogenic small LDL particles) are also involved in the development of coronary insufficiency. A precise knowledge of the diseases to be treated and their particularly rigorous prevention and treatment can improve the prognosis of coronary insufficiency in diabetics.
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PMID:[Treatment of coronary insufficiency in diabetics. Part 1: objectives and targets]. 1255 54

The morbidity and mortality associated with type 1 diabetes are essentially related to the micro- and macrovascular complications that develop over time and lead to several diabetic complications, including hypertension, atherosclerosis, and retinopathy, as well as coronary and renal failure. Normally absent in physiological conditions, the bradykinin B1 receptor (BKB1-R) was recently found to be overexpressed in pathological conditions, including type 1 diabetes. In the present study, we evaluated the effect of the new BKB1-R antagonist, R-954 (Ac-Orn-[Oic2, alpha-MePhe5, D-betaNal7, Ile8]desArg9-bradykinin, on the increase in vascular permeability in streptozotocin (STZ)-diabetic mice. The capillary permeability to albumin was measured by quantifying the extravasation of albumin-bound Evans blue dye in selected target tissues (liver, pancreas, duodenum, ileum, spleen, heart, kidney, stomach, skin, muscle, and thyroid gland). Acute single administration of R-954 (300 microg/kg, i.v.) to type 1 diabetic mice 4 weeks after STZ significantly inhibited the enhanced vascular permeability in most tissues. These data provide further experimental evidence for the implication of BKB1-R in the enhanced vascular permeability associated with type 1 diabetes.
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PMID:Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced vascular permeability in type 1 diabetic mice. 1256 48

In contrast to VEGF and its receptor VEGFR-2, PlGF and its receptor VEGFR-1 have been largely neglected and therefore their potential for therapy has not been previously explored. In this review, we describe the molecular properties of PlGF and VEGFR-1 and how this translates into an important role for PlGF in the angiogenic switch in pathological angiogenesis, by interacting with VEGFR-1 and synergizing with VEGF. PlGF was effective in the growth of new and stable vessels in cardiac and limb ischemia, through its action on different cell types (i.e. endothelial, smooth muscle and inflammatory cells and their precursors) that play a cardinal role in blood vessel formation. Accordingly, blocking its receptor VEGFR-1 with monoclonal antibodies (anti-VEGFR-1 mAb), expressed on al these cell types, successfully attenuated blood vessel formation during cancer, ischemic retinopathy and rheumatoid arthritis. In addition, while blocking this receptor was effective in reducing inflammatory disorders like atherosclerosis and rheumatoid arthritis, blocking the anti-angiogenic receptor VEGFR-2 was without effect. This indicates that in the latter diseases the beneficial effects of anti-VEGFR1 mAb were mainly due to its effect on inflammatory cells. Importantly, VEGFR-1 was also present on hematopoietic stem/progenitor cells, the precursors of inflammatory cells. Thus, these preclinical studies show proof-of-principle that PlGF and VEGFR-1 are promising therapeutic targets to treat angiogenesis and inflammation related disorders. Clinical trials will reveal whether this is also true for patients.
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PMID:Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. 1287 Dec 69

Impaired NO-dependent vasodilation of resistance vessels is an early marker of an increased risk of atherosclerosis; utility of the examination of microcirculation, however, is far less established. We have therefore tested the hypothesis that hypercholesterolemia is associated with an impaired microvascular reactivity and that this defect is at least partially reversible by lipid-lowering treatment. Twenty-seven otherwise healthy patients with severe hypercholesterolemia (HLP) were examined at rest and then after 10 weeks of atorvastatin treatment (20 mg/day). Skin microvascular reactivity (MVR) was examined by laser-Doppler flowmetry. Baseline MVR values of the studied group were compared to healthy control subjects, HLP patients with coronary artery disease (CAD) and diabetic patients with and without diabetic retinopathy. MVR was normal in HLP subjects without CAD. On the contrary, MVR was impaired in HLP patients with CAD. There was no effect of atorvastatin on MVR, despite the profound reduction of serum lipids. MVR values did not correlate with cholesterol levels. In diabetic subjects, the MVR was substantially impaired only in patients with retinopathy. In the subjects without retinopathy, MVR was either normal (type I diabetes) or moderately impaired (type II diabetes). MVR was thus normal in HLP patients without manifest vascular disease and was not influenced by lipid lowering therapy. Impairment in the MVR was only evident in subjects with HLP and severe CAD. These results suggest that microcirculation is not involved in the early vascular dysfunction induced by HLP and that MVR rather reflects changes which appear later in the course of the atherosclerotic disease.
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PMID:Microvascular reactivity in patients with hypercholesterolemia: effect of lipid lowering treatment. 1289 56

Especially the macrovascular risk and the reduced life expectancy emphasize that besides the optimal glycemic control in diabetes, the associated factors of metabolic syndrome, namely hypertension and hyperlipidemia, have to be treated with equal intensity. This will minimize additional diseases (e. g., atherosclerosis, nephropathy, retinopathy) and take some of the strain from our health care system in the long run. This article contains the current guidelines for the optimal treatment of hypertension and hyperlipidemia in diabetic patients.
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PMID:[Normalization of blood pressure and lipids in patients with diabetes]. 1293 2

We recently published the results of the Steno-2 study, which evaluated the benefits of intensified integrated behavior modification and targeted polypharmacy. The results provide abundant evidence that an ambitious treatment strategy is superior to a conventional one. The study involved 160 high-risk type 2 diabetic patients with microalbuminuria-a strong risk factor of both macrovascular and microvascular complications-aged 55.1 years, who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years. In the intensive group, a stepwise treatment plan was adopted involving both continuous lifestyle education and motivation and an ambitious goal-oriented pharmacological treatment of known modifiable risk factors. The conventional group was treated in accordance with national guidelines for type 2 diabetes with less stringent goals. The specific significant group differences in the degree of change in key clinical and biochemical variables at the end of the study were (in the intensive group): lower systolic and diastolic blood pressures, hemoglobin A(1c) (HbA(1c)), fasting serum total and low-density lipoprotein (LDL) cholesterol, fasting serum triglycerides, and 24-hour urine albumin excretion, as well as increased carbohydrate and decreased fat intake as percentage of total energy. There was no difference in weight gain between groups during follow-up and no other major side effects were reported. The primary end point was a macrovascular outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation for ischemia, or vascular surgery for peripheral arterial atherosclerosis. The differences between groups in surrogate end points translated into the following significant group differences in final clinical end points: 44% of patients in the conventional group had a cardiovascular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50%. Also, the relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group. In conclusion, an intensified and goal-oriented multipronged approach to the treatment of type 2 diabetes reduces cardiovascular events, as well as nephropathy, retinopathy, and autonomic neuropathy, by about half. The challenge is to ensure that this experience is widely adopted in daily practice.
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PMID:Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes: the Steno-2 study. 1293 35

Hypertension is a common clinical problem with great implications for public health. It is a silent killer and often remains asymptomatic. So regular BP check-up is a must. Complications of untreated hypertension include ventricular hypertrophy, heart failure and accelerated atherosclerosis, cerebrovascular disease and stroke, renal failure and retinopathy. Primary care physicians have immense duty to perform in this regard because they are the first to encounter them in various stages of the disease. Hypertension can present per se or in emergencies (as in crisis) or in disguise of a complication (like anaemia and renal failure). Control of hypertension and delaying the development of complications should be their first goal. Lastly, some hypertensives with complications may require referral to advanced centres.
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PMID:Complications of hypertension as encountered by primary care physician. 1296 46


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