Aims/hypothesis Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. Methods A prospectively planned group-level metaanalysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. Results A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% ( 2009 ) 52:2288 -2298 DOI 10.1007 /s00125-009-1470 treated participants had significantly more major hypoglycaemic events (HR 2.48,. Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89-1.13, vs HR 0.84, 95% CI 0.74-0.94, respectively; interaction p=0.04). Conclusions/interpretation Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucoselowering regimens should be tailored to the individual.

Few studies have determined whether carotid artery intima-media thickness (IMT) is associated prospectively with risk of first ischemic stroke. In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measured by B-mode ultrasonography at six sites of the carotid arteries. The authors assessed the relation of mean IMT to stroke incidence over 6-9 years' follow-up (1987-1995) among 7,865 women and 6,349 men aged 45-64 years without prior stroke at baseline in four US communities. There were 90 incident ischemic stroke events for women and 109 for men. In sex-specific Cox proportional hazards models adjusting only for age, race, and community, the hazard rate ratios comparing extreme mean IMT values (> or =1 mm) to values less than 0.6 mm were 8.5 for women (95% confidence interval: 3.5, 20.7) and 3.6 for men (95% confidence interval: 1.5, 9.2). The relation was graded, and models with cubic splines indicated significant nonlinearity, with hazards increasing more rapidly at lower IMTs than at higher IMTs. Thus, models using linear IMT values substantially underestimate the strength of the association at lower IMTs. The strength of the association was reduced by the inclusion of putative stroke risk factors, but it remained elevated at higher IMTs. Hence, mean carotid IMT is a noninvasive predictor of future ischemic stroke incidence.

In patients with familial hypercholesterolemia, the use of torcetrapib with atorvastatin, as compared with atorvastatin alone, did not result in further reduction of progression of atherosclerosis, as assessed by a combined measure of carotid arterial-wall thickness, and was associated with progression of disease in the common carotid segment. These effects occurred despite a large increase in HDL cholesterol levels and a substantial decrease in levels of LDL cholesterol and triglycerides. (ClinicalTrials.gov number, NCT00136981 [ClinicalTrials.gov].).

Abstract-The objective of this study was to describe associations of retinal arteriolar abnormalities with clinical and subclinical manifestations of atherosclerosis and a broad group of risk factors for vascular disease. A biracial population of 8772 adults (aged 48 to 72 years) living in 4 communities was examined from 1993 to 1995 were studied for that purpose. Retinal arteriovenous nicking and focal arteriolar narrowing were determined by light-box grading of a 45°f undus photograph by use of a standardized protocol. Diameters of arterioles and venules were measured in digitized photographs, and a summary arteriolar-to-venular ratio was derived as an index of generalized arteriolar narrowing. Focal arteriolar narrowing was associated only with hypertension. Generalized arteriolar narrowing was associated with carotid plaque but not with any other evidence of atherosclerosis, either clinical (cardiovascular disease or stroke) or subclinical (carotid or popliteal artery thickness or lower limb obstructive disease), or with plasma cholesterol. It was also associated with smoking, with inflammatory markers (white blood cell count, fibrinogen, and reduced albumin), and with the triglyceride and high density lipoprotein cholesterol changes associated with inflammation. Arteriovenous nicking was inconsistently associated with subclinical atherosclerosis. It was not associated with cardiovascular disease, stroke, or plasma cholesterol. Arteriovenous nicking was associated with markers of inflammation and vascular endothelial dysfunction (von Willebrand factor and factor VIII). Arteriolar narrowing and nicking appear to be related to hypertension and inflammatory factors. Nicking may also be related to endothelial dysfunction. Results suggest that these arteriolar changes are pathologically distinct from atherosclerosis. Including their measurement in population studies may permit evaluation of the independent contribution of arteriolar disease to various ischemic diseases of the heart, brain, and other organs. Key Words: arteriosclerosis Ⅲ atherosclerosis Ⅲ epidemiology Ⅲ inflammation Ⅲ risk factors R etinal arteriolar abnormalities (eg, focal and generalized narrowing and arteriovenous nicking) have long been recognized as being related to hypertension even in the absence of diabetes mellitus. 1-6 They have also been described in persons without hypertension (or diabetes) and have then been attributed to other unspecified arteriosclerotic processes. Thus, although many studies have demonstrated the associations of hypertension with retinal arteriolar changes in people without diabetes, few have examined the associations of these arteriolar changes with other risk factors. 2,[7][8][9][10][11][12][13][14] The relationship of these arteriolar changes with atherosclerotic, inflammatory, and other pathogenic processes is largely unknown. In the present study, we describe the relationships of these arteriolar changes with clinical and subclinical manifestations of atherosclerosis and a broad group of risk factors for vas...