Abstract Background Myocardial tissue injury due to acute myocardial infarction (AMI) does not only occur in the myocardium that is supplied by the culprit lesion, but can also extend to the remote, non-infarcted myocardium. The prognostic implications of remote myocardium changes assessed by cardiac magnetic resonance (CMR) are not fully understood. The aim was to investigate the prognostic relevance of remote myocardium alterations assessed by CMR T1 mapping (native T1 and extracellular volume (ECV)) in patients after ST-segment elevation myocardial infarction (STEMI). Methods This study analyzed 491 STEMI patients treated with primary percutaneous coronary intervention (PCI) that were included in the prospective MARINA-STEMI study (NCT04113356). CMR imaging was performed 4 (Interquartile range [IQR]: 3-5) days after PCI. CMR images were analyzed for left ventricular (LV) function, standard infarct characteristics as well as native remote T1 and remote ECV. The primary clinical endpoint was the composite of all-cause mortality, re-infarction and new congestive heart failure (Major adverse cardiovascular events, MACE). Results Remote native T1 (median: 1009 [IQR: 979-1044] ms) was associated with female sex, peak NT-pro-BNP levels, peak hs-cTnT elevations, TIMI-risk score, admission Killip class, anterior infarct location, post-interventional TIMI-flow, LV ejection fraction and microvascular injury. Remote ECV (median: 26.37 [IQR: 24.28-29.27] %) was associated with age, female sex, peak NT-pro-BNP levels, diabetes, TIMI-risk score, admission Killip class, anterior infarct location, LV ejection fraction and microvascular injury. Over a median follow-up of 12 months (IQR: 12-13) after STEMI, 42 MACE outcomes occurred. Higher native remote T1-times (1018.5 [IQR: 997.0-1064.0] ms vs. 1007.0 [IQR: 977.0-1041.5] ms, p=0.033) as well as a higher remote ECV-values (28.07 vs. 26.27 %, p=0.009) were observed in patients with MACE. Multivariable Cox regression analysis demonstrated that remote ECV (hazard ratio (HR): 1.53 [confidence interval (CI): 1.07-2.19], p=0.020) but not native remote T1 associated with MACE. Conclusions A comprehensive assessment of the remote myocardium with native T1 and ECV provides prognostic information in a contemporary cohort of low risk STEMI patients. Remote ECV, but not remote native T1, was found to be an independent predictor of MACE.

Abstract Background Previous studies have reported sex differences in pre-procedural imaging characteristics of patients undergoing transcatheter aortic valve replacement (TAVR) evaluation. Whether these differences affect the outcome of computed tomography (CT)-guided or cardiac magnetic resonance (CMR)-guided TAVR has not been studied. Objectives This analysis aimed to evaluate sex-based differences in imaging findings and outcomes in patients undergoing TAVR for severe aortic valve stenosis. Methods This was a secondary analysis of the TAVR-CMR trial, a randomized clinical trial comparing TAVR planning by CT or CMR. Outcomes (based on the Valve Academic Research Consortium (VARC)–2 definition) with each imaging strategy were compared according to sex. Results Of 380 patient randomized into the TAVR-CMR trial, 194 (51.1%) were female and 186 (48.9%) were male. Of these, 267 patients eventually underwent TAVR (133 women (49.8%) and 134 men (50.2%), p=0.457). Imaging findings differed between the sexes for both imaging modalities. The comparison between CT and CMR to assess the access route and landing zone showed no difference in both women and men (all p>0.05). Implantation success was not significantly different between imaging strategies for both women (84.7% (CT group) vs. 93.2% (CMR group), p=0.11) and men (95.7% (CT group) vs. 93.8% (CMR group), p=0.61). All-cause mortality at 6 months was not significantly different between imaging strategies for both women (10.2% (CT group) vs. 8.1% (CMR group), p=0.68) and men (4.3% (CT group) vs. 9.4% (CMR group), p=0.24). Conclusions This secondary analysis has confirmed sex-related differences in pre-procedural imaging characteristics, with no influence of the imaging modality used. Similar outcomes were observed in both female and male patients when the TAVR was guided by either a CMR or a CT scan.

Abstract Background Circadian processes are suggested to influence ischemic injury in ST-segment elevation myocardial infarction (STEMI). Observational data suspect a circadian dependence of the occurrence of microvascular obstruction (MVO) in patients with STEMI. However, these observations derive from a small sample size and circadian variations in left ventricular function and myocardial damage after STEMI are still a matter of controversy. Purpose We aimed to investigate the association of time of day dependent symptom onset with left ventricular ejection fraction (LVEF), infarct size (IS) and MVO in a large cohort of STEMI patients treated with primary percutaneous coronary intervention (PCI). Methods This observational study investigated acute STEMI patients treated with primary PCI. Cardiac magnetic resonance (CMR) imaging was performed within 1 week after the index event for the determination of left ventricular function and infarct characteristics. The time of symptom onset was used to discriminate patients according to LVEF, IS as well as MVO occurrence and extent over a 24 hours cycle to evaluate circadian behavior. Results In final analysis, 889 acute STEMI patients treated with primary PCI with a delay of 189 [120-315] minutes were included. Median age of the overall cohort was 57 [51-66] years and 17% were female. Median LVEF was 49 [42-55]%, IS assumed 15.5 [8.0-24.7]% of left ventricular myocardial mass (LVMM) and MVO occurred in 57% of STEMI patients. No hourly differences between symptom onset and MVO occurrence (p=0.108), MVO extent (p=0.735), LVEF (p=0.644) and IS (p=0.722) have been evaluated. When comparing 3 hourly segments of symptom onset, no variations in MVO occurrence (p=0.114), MVO extent (p=0.308), LVEF (p=0.547) and IS (p=0.405) were observed. Conclusions No circadian variations in symptom onset and the occurrence and extent of MVO, LVEF and IS were observed in this large cohort of STEMI patients treated with primary PCI. Further research is needed to investigate the complex interplay between circadian processes and ischemic injury in this patient population.

Abstract Background The E-wave propagation index (EPI) is a novel echocardiographic measure for quantifying apical washout in the left ventricle (LV) and thus a promising marker of an elevated risk for LV thrombus. The association between EPI and LV thrombus has not been investigated in patients after ST-segment elevation myocardial infarction (STEMI). Purpose Aim was to determine, whether there is an association between EPI and LV thrombus development in STEMI patients treated with primary percutaneous coronary intervention (pPCI). Methods 665 STEMI patients treated with pPCI included in the prospective MARINA-STEMI cohort study (NCT04113356) were investigated. LV thrombus presence was diagnosed via contrast enhanced CMR a median of 4 (interquartile range [IQR] 3–5) days post-STEMI. EPI and left ventricular ejection fraction (LVEF) were measured using transthoracic echocardiography (TTE) a median of 2 ([IQR] 2–3) days post-STEMI. The longitudinal length of the LV was measured in the apical 4-chamber view at end-diastole. Velocity time integral (VTI) of the E-wave was measured using pulsed wave doppler. Results 5% (n=32) of the study population had a LV thrombus. Patients with LV thrombus had lower EPI values compared to patients without LV thrombus (0.92 vs 1.29, p<0.001). EPI (OR 0.21, 95% CI: 0.06-0.73, p<0.014), anterior infarct location (OR 17.18, 95 % CI: 2.25-131.05, p<0.006) and LVEF (OR 0.91, 95 % CI 0.86-0.95, p<0.001) were independently associated with LV thrombus. The optimal cut-off value for the prediction of LV thrombus prediction was an EPI <1 (sensitivity 56.3% and specificity 80.4%). 13% (n=18) of patients with an EPI <1 developed a LV thrombus compared to 3% (n=14) with an EPI≥1. Conclusion In STEMI patients treated with pPCI, a decreased EPI is a novel independent predictor for CMR verified LV thrombus. The optimal cut off for LV thrombus prediction is EPI <1.Center Image EPI

Abstract Background and Aims Patients with STEMI are at significant risk for developing left ventricular thrombi (LVT). However, this complication often (up to 65%) remains undetected by using transthoracic echocardiography (TTE), referred to as TTE-occult LVT. The aim of this study was to investigate predictors of TTE-occult LVT and to propose a clinical model for improved detection of TTE-occult LVT post ST-elevation myocardial infarction (STEMI). Methods In total, 870 STEMI patients underwent TTE and cardiac magnetic resonance (CMR), the reference method for LVT detection, 3 days after infarction. Clinical and echocardiographic predictors were analyzed. Primary endpoint was the presence of TTE-occult LVT identified by CMR-Imaging. Results From the overall cohort, 37 patients (4%) showed an LVT by CMR. Of these thrombi, 25 (68%) were not identified by TTE. TTE-occult thrombi did not significantly differ in volume (1.4 vs. 2.74cm3), diameter (19.0 vs. 23.3mm), number of fragments or shape compared with TTE-apparent LVT (all p>0.05). For predicting these TTE-occult LVT, apical wall motion score using the 16-segment model (AWMS16Seg) showed highest validity (AUC:0.91 [95%CI:0.89-0.93];p<0.001), with an association independent of ejection fraction and AWMS17Seg (OR:1.68 [95%CI:1.43-1.97];p<0.001), clinical (body mass index, peak troponin) and angiographic (culprit lesion, post-interventional TIMI flow) associates of TTE-occult LVT (all p<0.05). Dichotomization at AWMS16Seg≥8 (n=260, 30%) allowed for a detection of all TTE-occult LVT (sensitivity:100%), with a corresponding specificity of 77%. Conclusions After acute STEMI, AWMS16Segserved as simple and very robust predictor of TTE-occult LVT. An AWMS16Seg-based algorithm to identify patients for additional CMR-imaging offers great potential to optimize detection of TTE-occult LVT following STEMI.Key IllustrationProposed Algorithm

Background Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances.Methods We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease.Findings Analyses included data for 698 782 people (52765 non-fatal or fatal vascular outcomes; 8.49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2.00 (95% CI 1.83-2.19) for coronary heart disease; 2.27 (1.95-2.65) for ischaemic stroke; 1.56 (1.19-2.05) for haemorrhagic stroke; 1.84 (1.59-2.13) for unclassified stroke; and 1.73 (1.51-1.98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40-59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10-12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3.90 mmol/L and 5.59 mmol/L. Compared with fasting blood glucose concentrations of 3.90-5.59 mmol/L, HRs for coronary heart disease were: 1.07 (0.97-1.18) for lower than 3.90 mmol/L; 1.11 (1.04-1.18) for 5.60-6-09 mmol/L; and 1.17 (1.08-1.26) for 6.10-6.99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors.Interpretation Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and nonlinearly associated with risk of vascular disease.

OBJECTIVES The purpose of this work was to determine the predictive value of oxidized phospholipids (OxPLs) present on apolipoprotein B-100 particles (apoB) in carotid and femoral atherosclerosis. BACKGROUND The OxPLs are pro-inflammatory and pro-atherogenic and may be detected using the antibody E06 (OxPL/apoB). METHODS The Bruneck study is a prospective population-based survey of 40to 79-year-old men and women initiated in 1990. Plasma levels of OxPL/apoB and lipoprotein (a) [Lp(a)] were measured in 765 of 826 (92.6%) and 671 of 684 (98.1%) subjects alive in 1995 and 2000, respectively, and correlated with ultrasound measures of carotid and femoral atherosclerosis. RESULTS The distribution of the OxPL/apoB levels was skewed to lower levels and nearly identical to Lp(a) levels. The OxPL/apoB and Lp(a) levels were highly correlated (r 0.87, p 0.001), and displayed long-term stability and lacked correlations with most cardiovascular risk factors and lifestyle variables. The number of apolipoprotein (a) kringle IV-2 repeats was inversely related to Lp(a) mass (r 0.48, p 0.001) and OxPL/apoB levels (r 0.46, p 0.001). In multivariable analysis, OxPL/apoB levels were strongly and significantly associated with the presence, extent, and development (1995 to 2000) of carotid and femoral atherosclerosis and predicted the presence of symptomatic cardiovascular disease. Both OxPL/apoB and Lp(a) levels showed similar associations with atherosclerosis severity and progression, suggesting a common biological influence on atherogenesis. CONCLUSIONS This study suggests that pro-inflammatory oxidized phospholipids, present primarily on Lp(a), are significant predictors of the presence and extent of carotid and femoral atherosclerosis, development of new lesions, and increased risk of cardiovascular events. The OxPL biomarkers may provide valuable insights into diagnosing and monitoring cardiovascular disease. (J Am Coll Cardiol 2006;47:2219–28) © 2006 by the American College of ublished by Elsevier Inc. doi:10.1016/j.jacc.2006.03.001

AIMS:In diabetic patients, increased urinary albumin excretion (UAE), termed microalbuminuria when in the range between 30 and 300 mg/dL per day, is associated with a higher risk of atherosclerosis and its complications. Whether or not this notion applies to the general population is a matter of ongoing controversy because none of the few previous investigations among non-diabetics strictly represent the general community.METHODS AND RESULTS:Urinary albumin-to-creatinine ratio (uACR), a measure of UAE, was assessed from overnight spot urine samples in a population-based cohort of 684 individuals. The ratio was significantly related to age, gender, blood pressure, diabetes, markers of systemic inflammation, liver enzymes, and parathyroid hormone levels (P<0.001 each). Moreover, uACR emerged as a highly significant risk predictor of carotid and femoral artery atherosclerosis in the general community and the non-diabetic subpopulation alike (age/sex-adjusted P<0.001 each). In multivariable logistic regression analyses, odds ratios (95% CI) of carotid and femoral atherosclerosis amounted to 1.28 (1.01-1.61) and 1.44 (1.15-1.81) for a one unit increase in log(e)-transformed uACR (P=0.040 and 0.002). Corresponding odds ratios in non-diabetic subjects were 1.41 (1.09-1.84) and 1.54 (1.19-1.99) (P=0.010 and 0.001). Multivariable linear regression analyses yielded significant, or near significant, relations with carotid and femoral artery intima-media thickness and atherosclerosis scores (P=0.058-0.001).CONCLUSION:The uACR is significantly and independently associated with the presence and severity of atherosclerosis in the general population. The relation obtained was of a dose-response type and extended to levels far below what is termed microalbuminuria. The novel aspects of our study are its focus on various vascular territories and representivity of the general healthy population.

Background and Purpose— Previous work has shown that soluble heat shock protein 60 (HSP60; sHSP60), present in circulating blood, is associated with carotid atherosclerosis. In the current evaluation, we tested the hypothesis that sHSP60 levels are associated with the progression of carotid arteriosclerosis, prospectively. Methods— The association of sHSP60 with early atherogenesis (5-year development and progression of nonstenotic carotid plaques) was investigated as part of the population-based prospective Bruneck Study. The current study focused on the follow-up period between 1995 and 2000 and, thus, included 684 subjects. Results— sHSP60 levels measured in 1995 and 2000 were highly correlated ( r =0.40; P <0.001), indicating consistency over a 5-year period. Circulating HSP60 levels were significantly correlated with antilipopolysaccharide and anti-HSP60 antibodies. It was also elevated in subjects with chronic infection (top quintile group of HSP60, among subjects with and without chronic infection: 23.8% versus 17.0%; P =0.003 after adjustment for age and sex). HSP60 levels were significantly associated with early atherogenesis, both in the entire population (multivariate odds ratio, for a comparison between quintile group V versus I+II: 2.0 [1.2 to 3.5] and the subgroup free of atherosclerosis at the 1995 baseline: 3.8 [1.6 to 8.9]). The risk of early atherogenesis was additionally amplified when high-sHSP60 and chronic infection were present together. Conclusions— Our study provides the first prospective data confirming an association between high levels of sHSP60 and early carotid atherosclerosis. This possibly indicates an involvement of sHSP60 in activating proinflammatory processes associated with early vessel pathology.

Incidence rates and risk factors for type 2 diabetes in low-risk populations are not well documented. We investigated these in white individuals who were aged 40-79 years and from the population of Bruneck, Italy. Of an age- and sex-stratified random sample of 1,000 individuals who were identified in 1990, 919 underwent an oral glucose tolerance test (OGTT) and an assessment of physiological risk factors for diabetes, including insulin resistance (homeostasis model assessment, HOMA-IR), and postchallenge insulin response (Sluiter's Index). Diabetes at baseline by fasting or 2-h OGTT plasma glucose (World Health Organization criteria, n = 82) was excluded, leaving 837 individuals who were followed for 10 years. Incident cases of diabetes were ascertained by confirmed diabetes treatment or a fasting glucose >or=7.0 mmol/l. At follow-up, 64 individuals had developed diabetes, corresponding to a population-standardized incidence rate of 7.6 per 1,000 person-years. Sex- and age-adjusted incidence rates were elevated 11-fold in individuals with impaired fasting glucose at baseline, 4-fold in those with impaired glucose tolerance, 3-fold in overweight individuals, 10-fold in obese individuals, and approximately 2-fold in individuals with dyslipidemia or hypertension. Incidence rates increased with increasing HOMA-IR and decreasing Sluiter's Index. As compared with normal insulin sensitivity and normal insulin response, individuals with low insulin sensitivity and low insulin response had a sevenfold higher risk of diabetes. Baseline impaired fasting glucose, BMI, HOMA-IR, and Sluiter's Index were the only independent predictors of incident diabetes in multivariate analyses. We conclude that approximately 1% of European white individuals aged 40-79 years develop type 2 diabetes annually and that "subdiabetic" hyperglycemia, obesity, insulin resistance, and impaired insulin response to glucose are independent predictors of diabetes.

Leptin, a key regulator of body weight ( 1 Ahima R.S. Flier J.S. Leptin. Ann Rev Physiol. 2000; 62: 413-437 Crossref PubMed Scopus (1466) Google Scholar ), has also been proposed as a regulator of bone mass ( 2 Cock T.A. Auwers J. Leptin cutting the fat off the bone. Lancet. 2003; 362: 1572-1574 Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar ). Rodents treated with leptin show increased bone mass and reduced skeletal fragility ( 3 Cornish J. Callon K.E. Bava U. et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol. 2002; 175: 405-415 Crossref PubMed Scopus (375) Google Scholar , 4 Burguera B. Hofbauer L.C. Thomas T. et al. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology. 2001; 142: 3546-3553 Crossref PubMed Scopus (240) Google Scholar ). Leptin may act on bone via binding to specific receptors on osteoblasts ( 3 Cornish J. Callon K.E. Bava U. et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol. 2002; 175: 405-415 Crossref PubMed Scopus (375) Google Scholar , 4 Burguera B. Hofbauer L.C. Thomas T. et al. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology. 2001; 142: 3546-3553 Crossref PubMed Scopus (240) Google Scholar , 5 Holloway W.R. Collier F.M. Aitken C.J. et al. Leptin inhibits osteoclast generation. J Bone Miner Res. 2002; 17: 200-209 Crossref PubMed Scopus (340) Google Scholar , 6 Thomas T. Gori F. Khosla S. et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology. 1999; 140: 1630-1638 Crossref PubMed Scopus (566) Google Scholar , 7 Reseland J.E. Syversen U. Bakke I. et al. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res. 2001; 16: 1426-1433 Crossref PubMed Scopus (304) Google Scholar ). In line with these findings, leptin receptor–deficient obese fa/fa rats have low bone mass ( 8 Foldes J. Shih M.S. Levy J. Bone structure and calcium metabolism in obese Zucker rats. Int J Obes Relat Metab Disord. 1992; 16: 95-102 PubMed Google Scholar , 9 Picherit C. Horcajada M.N. Mathey J. et al. Isoflavone consumption does not increase the bone mass in osteopenic obese female zucker rats. Ann Nutr Metab. 2003; 47: 70-77 Crossref PubMed Scopus (20) Google Scholar , 10 Tamasi J.A. Arey B.J. Bertolini D.R. Feyen J.H. Characterization of bone structure in leptin receptor-deficient Zucker (fa/fa) rats. J Bone Miner Res. 2003; 18: 1605-1611 Crossref PubMed Scopus (58) Google Scholar ). In contrast, results from studies of the bone phenotype of leptin-deficient ob/ob mice are conflicting; one study demonstrated low bone mass, whereas another showed that leptin-deficient ob/ob mice as well as leptin receptor–deficient db/db mice had increased bone mass due to increased osteoblast activity ( 11 Ducy P. Amling M. Takeda S. et al. Leptin inhibits bone formation through a hypothalamic relay a central control of bone mass. Cell. 2000; 100: 197-207 Abstract Full Text Full Text PDF PubMed Scopus (1755) Google Scholar , 12 Takeda S. Elefteriou F. Levasseur R. et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002; 111: 305-317 Abstract Full Text Full Text PDF PubMed Scopus (1324) Google Scholar , 13 Matsunuma A. Kawane T. Maeda T. et al. Leptin corrects increased gene expression of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase and -24-hydroxylase in leptin-deficient, ob/ob mice. Endocrinology. 2004; 14: 1367-1375 Google Scholar ).

OBJECTIVES: The present study aimed at evaluating the prevalence of the Metabolic Syndrome and at identifying its additional clinical features. RESEARCH DESIGN AND METHODS: Within a prospective population-based survey examining 888 subjects aged 40–79 y, subjects were identified fulfilling the WHO and the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria for diagnosing the Metabolic Syndrome. In these subjects and in the rest of the sample (controls), several metabolic and nonmetabolic biochemical parameters were compared. RESULTS: The prevalence of the Metabolic Syndrome by WHO criteria was 34.1% (95% CI 31.0–37.2) and by NCEP-ATPIII criteria 17.8% (15.5–20.3). The prevalence was significantly higher in older subjects and in those less physically active. Subjects with the Metabolic Syndrome either by WHO or by NCEP-ATPIII criteria showed higher levels of oxidized low-density lipoprotein, apolipoprotein B, urate, leptin, fibrinogen, leukocytes, erythrocyte sedimentation rate, GOT, gamma-GT and soluble endothelial adhesion molecules (E-selectin, vascular adhesion molecule-1 and intercellular adhesion molecule-1) and lower apolipoprotein A concentrations. Insulin resistance, as assessed by the Homeostasis Model Assessment, increased with the increase in the number of traits composing the syndrome found within the single individual. Subjects with insulin resistance had more pronounced abnormalities in several parameters, including the additional features of the syndrome (eg fibrinogen and soluble adhesion molecules). CONCLUSIONS: The Metabolic Syndrome occurs very frequently in the general population aged 40–79 y, and is associated with several additional metabolic and nonmetabolic abnormalities that likely contribute to an increased cardiovascular risk. Insulin resistance seems to play a major role in classic and additional abnormalities featuring the Metabolic Syndrome.

OBJECTIVE - The present study aimed at prospectively evaluating carotid atherosclerosis and coronary heart disease (CHD) in subjects with the metabolic syndrome.RESEARCH, DESIGN AND METHODS - Within a prospective population-based survey examining 888 subjects aged 40-79 years, 303 subjects were identified as fulfilling World Health Organization (WHO) criteria and 158 as fulfilling the National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria for diagnosing the metabolic syndrome. The 5-year change in carotid status, as assessed by echo-duplex scanning, and incident fatal and nonfatal CHD, as assessed by medical history and death certificates, were compared in subjects with the metabolic syndrome and in the rest of the sample (control subjects).RESULTS - Compared with the control subjects, subjects with the metabolic syndrome by WHO criteria had an increased 5-year incidence and progression of carotid atherosclerosis: 51 vs. 35% developed new plaques (P = 0.021) and 34 vs. 19% developed carotid stenosis >40% (P = 0.002) after adjusting for several confounders. Subjects with the metabolic syndrome by these criteria also had an increased incidence of CHD during follow-up: 8 vs. 3% in control subjects (P = 0.012). Similar results were found when the NCEP-ATPIII criteria were used.CONCLUSIONS - Subjects with the metabolic syndrome are at increased risk for both progressive carotid atherosclerosis and CHD.

The present study aimed at evaluating the prevalence of the Metabolic Syndrome, as assessed by WMO criteria, its ancillary clinical features and its risk of atherosclerosis and cardiovascular disease.We examined a population-based sample of 888 subjects, aged 40-79 years, living in Bruneck (northeastern Italy), among whom we identified subjects fulfilling the WHO criteria for diagnosing the Metabolic Syndrome. In these subjects and in the rest of the sample (Controls), several metabolic and nonmetabolic biochemical parameters were compared, and the 5-year change in carotid atherosclerosis (CA), and incident fatal and nonfatal coronary heart disease (CHD) were determined.The prevalence of the Metabolic Syndrome was 34.1%. Subjects with the Syndrome showed higher levels of oxidized low-density lipoprotein (LDL), apolipoprotein B, urate, leptin, fibrinogen, leukocytes, erythrocyte sedimentation rate (ESR), GOT, gamma-GT and soluble endothelial adhesion molecules (E-selectin, Vascular Adhesion Molecule-1/VCAM-1 and Intercellular Adhesion Molecule-1/ICAM-1), and lower apolipoprotein A concentrations. Insulin resistance increased with the increase in the number of abnormalities composing the Syndrome. Subjects with insulin resistance had more pronounced abnormalities in several classic and nonclassic parameters. Subjects with the Metabolic Syndrome had an increased 5-year incidence and progression of CA and incidence of CHD.The Metabolic Syndrome, in which insulin resistance plays a major role, occurs very frequently in the general population, has several ancillary features and is burdened by an increased risk of atherosclerosis and cardiovascular disease. (C) 2003 Elsevier Science B.V. All rights reserved.

BACKGROUND AND PURPOSE:Susceptibility of the vasculature to the injurious effects of smoking varies substantially, with some smokers developing severe premature atherosclerosis and others remaining free of advanced atheroma until high ages. The present study sought to estimate the contribution of chronic infections to the variability of atherosclerosis severity among smokers.METHODS:In the community-based Bruneck Study, 5-year changes in carotid atherosclerosis were assessed by high-resolution ultrasound. Early atherogenesis was defined by the development of nonstenotic plaques and advanced atherogenesis by the development/progression of vessel stenosis >40%.RESULTS:The risk of early atherogenesis strongly relied on lifetime smoking exposure and remained elevated long-term after cessation of smoking. Remarkably, current and ex-smokers faced an increased atherosclerosis risk only in the presence of chronic infections (odds ratios [95% CIs], 3.3 [1.8 to 6.2] and 3.4 [1.8 to 6.3]; P<0.001 each), whereas current, past, and nonsmokers without infections did not differ substantially in their estimated risk burden (odds ratios [95% CIs], 1.4 [0.8 to 2.4], 0.9 [0.6 to 1.6], and 1.0 [reference group]). In analogy to first-hand smoking, subjects exposed to environmental tobacco smoke were found to be vulnerable to the manifestation of chronic infection, and only those infected experienced a high atherosclerosis risk. The risk of advanced atherogenesis showed a dose-response relation with the number of daily cigarettes, returned to normal shortly after cessation of smoking, and emerged as independent of infectious illness.CONCLUSIONS:Our study provides the first epidemiological evidence that the proatherogenic effects of cigarette smoking are mediated in part by the chronic infections found in smokers. A better understanding of the vascular pathogenetic mechanisms of smoking may offer novel clues for disease prevention supplementary to the primary goal of achieving long-term abstinence.

BACKGROUND:Chronic infections have been implicated in the pathogenesis of atherosclerosis, yet from an epidemiological perspective, this concept remains controversial.METHODS AND RESULTS:The Bruneck Study is a prospective population-based survey on the pathogenesis of atherosclerosis. In 826 men and women 40 to 79 years old (1990 baseline), 5-year changes in carotid atherosclerosis were thoroughly assessed by high-resolution duplex scanning. The presence of chronic respiratory, urinary tract, dental, and other infections was ascertained by standard diagnostic criteria. Chronic infections amplified the risk of atherosclerosis development in the carotid arteries. The association was most pronounced in subjects free of carotid atherosclerosis at baseline (age-/sex-adjusted odds ratio [95% CI] for any chronic infection versus none, 4.08 [2.42 to 6.85]; P:<0.0001) and applied to all types of chronic (bacterial) infections. It remained independently significant after adjustment for classic vascular risk attributes and extended to low-risk individuals free of conventional risk factors. Among subjects with chronic infections, atherosclerosis risk was highest in those with a prominent inflammatory response. Markers of systemic inflammation, such as soluble adhesion molecules and circulating bacterial endotoxin, and levels of soluble human heat-shock protein 60 and antibodies to mycobacterial heat-shock protein 65 were elevated in subjects with chronic infections and predictive of an increased risk of atherosclerosis.CONCLUSIONS:The present study provides solid evidence for a role of common chronic infections in human atherogenesis. Induction of systemic inflammation and autoimmunity may be potential pathophysiological links.

Background and purpose: A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids (alpha- and beta- carotene, lutein, lycopene, zeaxanthin, beta -cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries. Methods: This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45-65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound. Results: alpha- and beta- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries (P = 0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries (P = 0.04). These findings were obtained after adjustment for other cardiovascular risk factors (sex, age, LDL (low density lipoproteins), ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein). Atherosclerosis risk gradually decreased with increasing plasma alpha- and beta -carotene concentrations (p = 0.004). No associations were found between vitamin A and E plasma levels and atherosclerosis. Conclusions: This study provides further epidemiological evidence of a protective role of high alpha- and beta- carotene in early atherogenesis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.