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Vascular aging is a major contributor to cardiovascular disease and can be quantified by higher carotid stiffness, intima-media thickness and diameter, and hypertension. Weight gain across the lifetime may be an important, modifiable determinant of vascular aging. We therefore aimed to assess lifetime body silhouette trajectories (a marker of weight change across the lifespan) in relation to vascular aging in late adulthood. We used cross-sectional data from a community-based cohort study (n=8243; age, 59.4; 38.7% women). A linear mixed model was used to assess trajectories of recalled body silhouettes from age 8 to 45 years. We assessed carotid artery properties (ultrasonography), resting hypertension (blood pressure ≥140/90 mm Hg or use of antihypertensives), and exaggerated exercise blood pressure, a marker of masked hypertension (systolic blood pressure ≥150 mm Hg during submaximal exercise) at study recruitment when the participants were 50 to 75 years of age. We identified 5 distinct body silhouette trajectories: lean stable (32.0%), lean increase (11.1%), moderate stable (32.5%), lean-marked increase (16.3%), and heavy stable (8.1%). Compared with individuals in the lean-stable trajectory, those in the moderate-stable, lean-marked increase, and heavy-stable trajectories had higher carotid stiffness, intima-media thickness and diameter (odds ratios between 1.23 and 2.10 for highest quartile versus lowest quartile of manifestations of vascular aging; P0.05) and were more likely to have resting hypertension and exaggerated exercise blood pressure, after adjustment for potential confounders (odds ratios between 1.31 and 1.60; P0.05). Vascular aging was most prominent among individuals who were lean in early life but markedly gained weight during young adulthood and among those who were heavy in early life and maintained weight.

Background: Vascular aging, i.e. accumulation of functional and structural changes of vessels throughout life, is a major contributor to cardiovascular disease. It can be quantified by higher carotid stiffness, intima-media thickness and diameter, and hypertension. Weight gain across the lifetime may be an important, modifiable determinant of vascular aging. Aim: To assess lifetime body silhouette trajectories (a marker of weight change across the lifespan) in relation to vascular aging in late adulthood. Methods: We used cross-sectional data from a community-based study (n=8,083; age 59.4; 38.6% women). A linear mixed model was used to assess trajectories of recalled body silhouettes from age 8 to 45. We assessed carotid stiffness, IMT and diameter (ultrasonography), resting hypertension (blood pressure ≥140/90 mmHg or use of antihypertensives), and exaggerated exercise blood pressure, a marker of masked hypertension (systolic blood pressure ≥150 mmHg during submaximal exercise). Results: We identified 5 trajectories: lean-stable (32%), lean-increase (11%), moderate-stable (33%), lean-marked increase (16%) and heavy-stable (8%). Compared to those in the lean-stable trajectory, individuals in the moderate-stable, lean-marked increase and heavy-stable trajectories had more evidence of vascular aging (Figure). Conclusions: Vascular aging was most prominent among individuals who were lean in early life but gained weight during young adulthood, and among those who were heavy in early life and maintained weight. This suggests that prevention of weight gain across the life course, especially during young adulthood, is important to promote healthy vascular aging.

Introduction: Late-life depression is related to poor quality of life, functional impairment, and increased risk of mortality and cardiovascular disease. Effective interventions for prevention and treatment of late-life depression need to be developed, which requires a better understanding of late-life depression risk factors. Arterial stiffness, an important cardiovascular disease risk factor, may contribute to late-life depression via cerebrovascular damage, but evidence is scarce. Aim: We investigated the association between carotid artery stiffness and incident depressive symptoms in a large community-based cohort study. Methods: This longitudinal study included 7,013 participants (60 (SD 6) years; 36% women) free of depressive symptoms at baseline. Carotid stiffness (high-resolution echotracking) was determined at baseline. Presence of depressive symptoms was determined at baseline and at 4 and 6 years of follow-up, and was defined as a score ≥7 on a validated 13-item questionnaire (Q2DA) and/or new use of antidepressants. Cox regression and generalized estimating equations (GEE) were used. Results: In total, 6.9% (n=484) of the participants had incident depressive symptoms at 4 or 6 years of follow-up. Greater carotid stiffness was associated with a higher incidence of depressive symptoms (Figure). Results were qualitatively similar when GEE was used instead of Cox regression. Conclusions: Greater carotid stiffness is associated with a higher incidence of depressive symptoms. This study supports the hypothesis that carotid stiffness contributes to the development of late-life depression.

Background: Physical activity (PA) is beneficial for baroreflex sensitivity (BRS), but it is unclear whether the type of PA has similar effects on the neural (nBRS) or vascular (carotid stiffness) components of BRS. We sought to determine this in healthy adults from a community- based study via assessment of occupational (OPA), sport (SPA), leisure (LPA) and total PA (TPA). Methods: In 8649 adults aged 50 to 75 years, resting nBRS (estimated by low frequency gain, from carotid distension rate and heart rate) and carotid stiffness were measured by high-precision carotid echotracking. PA was self-reported using the Baecke questionnaire, which distinguishes OPA, SPA, LPA and TPA. The associations between PA and nBRS and carotid stiffness were quantified using multivariate linear regression analysis. Analyses were conducted separately in the working and non- working population. Results: In working adults (n=5039), OPA was associated with lower nBRS function (p=0.026) and borderline higher carotid stiffness (p=0.08). The associations between OPA and nBRS remained independent after additionally adjusting for SPA (p=0.03) and exaggerated exercise blood pressure (p=0.005), a predictor of future hypertension and cardiovascular events. When examining the type of OPA separately (i.e. lifting heavy loads, standing or walking at work) lifting heavy loads only was associated with impaired nBRS (p=0.048). When stratified by education, this association remained only in those with less than tertiary education. SPA was associated with higher nBRS (p=0.0005) and borderline lower carotid stiffness (p=0.052). Neither LPA nor TPA was associated with nBRS or carotid stiffness. In non-working adults (n=3610), SPA and TPA were both associated with lower carotid stiffness (p=0.012 and p=0.020), but not nBRS. LPA was not associated with either parameter. Conclusion: Occupation-related PA, in particular lifting heavy loads, is associated with lower nBRS function, especially in those with lower education. Higher amounts of sport-related PA are associated with higher nBRS and lower carotid stiffness.

Depression is twice as common in type 2 diabetes as in the general population and is associated with adverse health outcomes. Growing evidence suggest that type 2 diabetes and depression share biological mechanisms. This brief commentary discusses current understanding of shared biological pathways, focussing on hyperglycaemia, (micro)vascular dysfunction, and low-grade inflammation. Although there is accumulating evidence that these pathways are involved in the link between type 2 diabetes and depression, direct evidence of their temporal associations is lacking because of a paucity of longitudinal studies that focus on the pathobiology of both type 2 diabetes and depression.

Carotid arterial diameter enlargement is a manifestation of arterial remodeling and may be a risk factor for cardiovascular disease (CVD). We evaluated the association between carotid artery diameter and risk of stroke, coronary heart disease, CVD, and all-cause mortality and explored whether the associations could be explained by processes involved in arterial remodeling, that is, blood pressure–related media thickening, arterial stiffness, arterial wall stress, and atherosclerosis. We included 4887 participants (mean age 67±9 years; 54% women) from 4 cohort studies: Rotterdam Study, NEPHROTEST, Hoorn Study, and a study by Blacher et al. Common carotid artery properties were measured using echotracking. Incident cases were recorded based on medical records. We used Cox proportional hazard models adjusting for cardiovascular risk factors and estimates of processes underlying arterial remodeling. During follow-up (mean, 11 years), 379 (8%) individuals had a stroke, 516 had a (11%) coronary heart disease, 807 had a (17%) CVD, and 1486 (30%) had died. After adjustment for cardiovascular risk factors, individuals in the highest tertile of carotid diameter (diameter >8 mm) compared with those in the lowest tertile (diameter

Objective:Arterial stiffness may be a mechanism to explain the association between uric acid and cardiovascular disease. We aimed to analyse associations between serum uric acid and regional and local arterial stiffness, and assess potential differences related to sex and glucose metabolism status.Methods:A cross-sectional study was performed in 614 adults [52.6% men; mean age 58.7 +/- 8.5 years; 23.2% type 2 diabetes mellitus (by design)] from The Maastricht Study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), distensibility, and compliance coefficient of the carotid and femoral artery, and carotid artery Young's elastic modulus.Results:Higher uric acid (per SD of 74 mu mol/l) was associated with greater stiffness indicated by a significantly higher cfPWV [beta = 0.216 (95% confidence interval 0.061, 0.372); P = 0.006] and lower carotid distensibility coefficient [beta = -0.633 (95% confidence interval -1.099, -0.166); P = 0.008] after adjustment for sex, age, and glucose metabolism status. Associations lost significance after adjusting for mean arterial pressure, BMI, waist, smoking status, heart rate, total : high-density lipoprotein cholesterol ratio, triglycerides, estimated glomerular filtration rate, use of lipid-lowering, antihypertensive, and diabetes medication, and use of secondary uricosurics. No associations were found between uric acid and carotid compliance coefficient, carotid Young's elastic modulus, or stiffness of the femoral artery. A significant interaction (P Conclusion:Uric acid was not significantly associated with stiffness of the aorta, or the carotid or femoral artery among adults aged 40-75 years without and with type 2 diabetes mellitus.

MRI features of cerebral small vessel disease (CSVD), i.e. white matter hyperintensities, lacunes, microbleeds, perivascular spaces, and cerebral atrophy, may be associated with clinical events, but the strength of these associations remains unclear. We conducted a systematic review and meta-analysis on the association between these features and incident ischaemic and haemorrhagic stroke, all-cause dementia and depression, and all-cause mortality. For the association with stroke, 36 studies were identified (number of individuals/events [n] = 38,432/4,136), for dementia 28 (n = 16,458/1,709), for depression nine (n = 9,538/1,746), and for mortality 28 (n = 23,031/2,558). Only two studies evaluated perivascular spaces; these results were not pooled. Pooled analyses showed that all other features were associated with all outcomes (hazard ratios ranged 1.22–2.72). Combinations of two features were more strongly associated with stroke than any individual feature. Individual features and combinations of CSVD features are strongly associated with incident ischaemic and haemorrhagic stroke, all-cause dementia and depression, and all-cause mortality. If these associations are causal, the strength of these associations suggests that a substantial burden of disease is attributable to CSVD.

Adverse Event A drug interaction leading to higher exposure to cyclosporine. Drugs Implicated Cyclosporine and ticagrelor. The Patient A 49-year-old man with a stable renal graft, managed with cyclosporine with stable trough blood concentrations for several years, was treated with ticagrelor for unstable angina pectoris. Evidence That Links the Drug to the Event The timeline was consistent with the appearance of an interaction, the interaction was confirmed by an increase in trough concentration of cyclosporine, and there were no alternative causes that by themselves could have caused the increase in cyclosporine exposure. Management Cessation of ticagrelor. Mechanism Inhibition of CYP3A4 and P-glycoprotein by ticagrelor. Implications for Therapy Clinicians should be aware of this potential interaction as ticagrelor is frequently prescribed in individuals using cyclosporine. Close monitoring of cyclosporine serum concentrations is warranted to avoid overdosing of cyclosporine. A pharmacokinetic study is needed to further examine the probable interaction between cyclosporine and ticagrelor.

Objective: In type 2 diabetes (T2D), increased arterial stiffening results from accelerated arterial wall matrix remodeling. The associated structural alterations modify the pressure dependency of arterial stiffness, which can be quantified by the systolic-diastolic difference in carotid pulse wave velocity (delta PWV). We evaluated the association between T2D and dPWV as marker for matrix remodeling and whether dPWV may contain additional information beyond carotid stiffness (cPWV).Methods: In 746 individuals from The Maastricht Study, 415 with normal glucose metabolism; 126 with prediabetes; and 205 with T2D, carotid pulse wave velocity (cPWV) and dPWV were determined by ultrasonography and tonometry. Multiple linear regression analyses were used to investigate associations of glucose metabolism status (with normal glucose metabolism as reference) with cPWV and dPWV, adjusting for age, sex, mean arterial pressure, prior cardiovascular disease, estimated glomerular filtration rate and smoking, and dPWV or cPWV as appropriate.Results: After adjustment for age, sex, mean arterial pressure, prior cardiovascular disease, estimated glomerular filtration rate and smoking, T2D was associated with greater cPWV [beta(95% confidence interval) 0.376 (0.119; 0.632)] and delta PWV [0.301 (0.013; 0.589)]. After additional adjustment for dPWV or cPWV, associations of T2D with cPWV and dPWV were attenuated [0.294 (0.048; 0.539) and 0.173 (-0.103; 0.449), respectively]. Prediabetes was not associated with either cPWV or dPWV.Conclusion: The systolic-diastolic difference in carotid stiffness is increased in T2D, but not prediabetes. Importantly, the association was not abolished by carotid stiffness, which suggests that systolic-diastolic difference in carotid stiffness carries additional information regarding arterial matrix remodeling.

Objectives This study sought to investigate the association of local and segmental arterial stiffness with incident cardiovascular events and all-cause mortality. Background The association of different stiffness indices, in particular of carotid, brachial, and femoral stiffness, with cardiovascular disease and mortality is currently unknown. Methods In a population-based cohort (n = 579, mean age 67 years, 50% women, 23% with type 2 diabetes [by design]), we assessed local stiffness of carotid, femoral, and brachial arteries (by ultrasonography), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index, and systemic arterial compliance. Results After a median follow-up of 7.6 years, 130 participants had a cardiovascular event and 96 had died. The hazard ratios (HRs) (95% confidence intervals [CIs]) per 1 SD for cardiovascular events and all-cause mortality, respectively, were HR: 1.22 (95% CI: 0.95 to 1.56) and 1.51 (95% CI: 1.11 to 2.06) for lower carotid distensibility; HR: 1.19 (95% CI: 1.00 to 1.41) and 1.28 (95% CI: 1.07 to 1.53) for higher carotid elastic modulus; HR: 1.08 (95% CI: 0.88 to 1.31) and 1.43 (95% CI: 1.10 to 1.86) for lower carotid compliance; HR: 1.39 (95% CI: 1.06 to 1.83) and 1.27 (95% CI: 0.90 to 1.79) for lower femoral distensibility; HR: 1.25 (95% CI: 0.96 to 1.63) and 1.47 (95% CI: 1.01 to 2.13) for lower femoral compliance; and HR: 1.56 (95% CI: 1.23 to 1.98) and 1.13 (95% CI: 0.83 to 1.54) for higher cfPWV. These results were adjusted for age, sex, mean arterial pressure, and cardiovascular risk factors. Mutual adjustments for each of the other stiffness indices did not materially change these results. Brachial stiffness, augmentation index, and systemic arterial compliance were not associated with cardiovascular events or mortality. Conclusions Carotid and femoral stiffness indices are independently associated with incident cardiovascular events and all-cause mortality. The strength of these associations with events may differ per stiffness parameter.

Arterial stiffening, as characterized by an increase in carotid–femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid–femoral pulse-wave velocity (sβ 0.10; 95% confidence interval, 0.03–0.17 and 0.10; 0.04–0.16, respectively) and central pulse pressure (sβ 0.08; 95% confidence interval 0.01–0.15 and 0.07; 0.01–0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid–femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus ( P -interaction

Carotid stiffening is considered an important element in the pathogenesis of cerebrovascular diseases. These include stroke as well as vascular dementia and depression. However, results of individual studies evaluating the association between carotid stiffening and incident stroke have been inconsistent. Therefore, we have conducted a systematic review and meta-analysis, showing that carotid stiffening is associated with incident stroke independently of cardiovascular risk factors and aortic stiffness. In addition, carotid stiffening improved stroke risk prediction beyond the Framingham stroke risk factors and aortic stiffness. Other studies have shown that carotid stiffening is associated with a higher incidence of vascular dementia and depressive symptoms. This suggests that carotid stiffness is a potential separate target for prevention strategies of cerebrovascular disease.

Aims We evaluated the associations of diabetic complications and underlying pathology with daily walking activity in type 2 diabetic patients without manifest mobility limitations. Methods 100 persons with type 2 diabetes (mean age 64.5 ± 9.4 years) were studied. Persons with manifest mobility limitations were excluded. Possible determinants measured: peripheral neuropathy, neuropathic pain, peripheral arterial disease, cardiovascular disease, decreased muscle strength (handgrip strength), BMI, depression, falls and fear of falling. Walking activity was measured during one week with a pedometer. Functional capacity was measured with the 6 min walk test, the timed “up and go” test and a stair climbing test. Results Prevalence of neuropathy (40%) and obesity (53%) was high. Persons took a median of 6429 steps/day. In multivariate regression analysis, adjusted for age and sex, neuropathy was associated with a reduction of 1967 steps/day, decreased muscle strength with 1782 steps/day, and an increase in BMI of 1 kg/m2 with a decrease of 210 steps/day (all p

An increasing number of individuals will face age-related cognitive difficulties, as life expectancy has increased globally. It is therefore important to identify modifiable risk factors for cognitive impairment. Very short- to mid-term blood pressure variability (BPV) may be such factor, as it may cause cerebral ischemia via various mechanisms. To this end, we investigated whether greater diastolic (dBPV) and systolic BPV (sBPV) are cross-sectionally associated with memory function (MF; n = 1804), information processing speed (IPS; n = 1793), and executive function (EF; n = 1780), in 40- to 75-year-old individuals from The Maastricht Study. A composite BPV-index was derived by standardizing and averaging within-visit, 24-hour and 7-day BPV. We performed linear regression with adjustments for age, sex, educational level, 24-hour DBP or SBP, and cardiovascular risk factors. We found that a 1-SD greater dBPV was associated with lower IPS (beta [SD difference]; 95% CI: -0.10;-0.20 to -0.00) and EF (-0.12; -0.22 to -0.01), and borderline associated with lower MF (-0.09; -0.20 to 0.01). A 1-SD greater sBPV, however, was not associated with IPS (-0.040; -0.14 to 0.06), or EF (-0.09; -0.20 to 0.022), but was borderline associated with lower MF (-0.11; -0.21 to 0.00). This effect of greater dBPV on cognitive performance is equivalent to ±3 additional years of ageing. The stronger association of dBPV than sBPV with cognitive performance may be explained by the fact that DBP is the main determinant of MAP. Excessive dBPV may then lead to inadequate cerebral perfusion. In conclusion, greater very short-to mid-term dBPV and, to a lesser extent, sBPV could be a modifiable risk factor for cognitive impairment.

Carotid stiffening is considered a key element in the pathogenesis of stroke. However, results of studies evaluating the association between carotid stiffness and incident stroke have been inconsistent.This study investigated whether carotid stiffness (as determined by ultrasonography) is associated with incident stroke and whether this association is independent of aortic stiffness as estimated by carotid-femoral pulse wave velocity (cfPWV). Additionally, we evaluated the incremental value of carotid stiffness for stroke risk prediction beyond Framingham risk factors and cfPWV.This study included a systematic review and meta-analyses of aggregate and individual participant data (IPD), the latter of which was obtained by requesting individual-level data of all cohort studies with available data on carotid stiffness and cfPWV.Ten studies (n = 22,472) were included in the aggregate data meta-analysis and 4 (n = 4,540) in the IPD meta-analysis. After adjusting for cardiovascular (CV) factors, the aggregate data meta-analysis showed that greater carotid stiffness (per SD) was associated with stroke (hazard ratio: 1.18; 95% confidence interval: 1.05 to 1.33). In addition, carotid stiffness was associated with total CV events and CV and all-cause mortality, but not with coronary heart disease events. In the IPD meta-analysis, additional adjustment for cfPWV did not materially change these associations. Carotid stiffness did improve stroke risk prediction beyond Framingham and cfPWV (integrative discrimination improvement: 0.4 percentage point [95% confidence interval: 0.1 to 0.6 percentage point] and continuous net reclassification improvement: 18.6% [95% confidence interval: 5.8% to 31.3%]).Carotid stiffness is associated with incident stroke independently of CV factors and aortic stiffness. In addition, carotid stiffness improves stroke risk prediction beyond Framingham and aortic stiffness.

Objective: The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) leads to depressive symptoms by disruption of brain structures involved in mood regulation. However, longitudinal data on the association between CSVD and depressive symptoms are scarce. The authors investigated the association between CSVD and incident depressive symptoms. Method: Longitudinal data were taken from the Age, Gene/Environment Susceptibility-Reykjavik Study of 1,949 participants free of dementia and without baseline depressive symptoms (mean age: 74.6 years [SD=4.61; women, 56.6%). MRI markers of CSVD, detected at baseline (2002-2006) and follow-up (2007-2011), included white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces, and total brain parenchyma volume. Incident depressive symptoms were defined by a score >= 6 on the 15-item Geriatric Depression Scale and/or use of antidepressant medication. Results: Depressive symptoms occurred in 10.1% of the participants. The association for a greater onset of depressive symptoms was significant for participants with 1 standard deviation increase in white matter hyperintensity volume over time, new subcortical infarcts, new Virchow-Robin spaces, 1 standard deviation lower total brain volume at baseline, and 1 standard deviation decreased total brain volume overtime, after adjustments for cognitive function and sociodemographic and cardiovascular factors. Results were qualitatively similar when change in the Geriatric Depression Scale score over time was used as the outcome instead of incident depressive symptoms. Conclusions: Most markers of progression of CSVD overtime and some markers of baseline CSVD are associated with concurrently developing new depressive symptoms. These findings support the vascular depression hypothesis.

Arterial stiffness may be a cause of cerebral small vessel disease and cognitive impairment. We therefore performed a systematic review and meta-analysis of studies on the association between stiffness, cerebral small vessel disease and cognitive impairment. For the associations between stiffness (i.e. carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PWV (baPWV), carotid stiffness and pulse pressure) on the one hand and cerebral small vessel disease and cognitive impairment on the other, we identified 23 (n=15,666/20 cross-sectional; 1 longitudinal; 2 combined cross-sectional/longitudinal) and 41 studies (n=57,671/26 cross-sectional; 11 longitudinal; 4 combined cross-sectional/longitudinal), respectively. Pooled analyses of cross-sectional studies showed that greater stiffness was associated with markers of cerebral small vessel disease with odds ratios, per +1 SD, of 1.29-1.32 (P

In recent clinical investigations, visit-to-visit systolic blood pressure (SBP) variability was proven as a predictor of cardiovascular events and all-cause mortality. However, inconsistent results exist in this association. A meta-analysis of 13 prospective studies was conducted to evaluate the prognostic value of visit-to-visit SBP variability by different parameters in 77,299 patients with a mean follow-up of 6.3 years. The pooled age- and mean SBP-adjusted hazard ratios (HRs) for all-cause mortality were 1.03 (95% confidence interval [CI], 1.02-1.04; P

International audience; BACKGROUND It has been hypothesized that arterial stiffness leads to generalized microvascular dysfunction and that individuals with type 2 diabetes mellitus (T2DM) are particularly prone to the detrimental effects of arterial stiffness. However, evidence for an association between stiffness and markers of generalized microvascular dysfunction is lacking. We therefore investigated the association between arterial stiffness and skin microvascular function in individuals without and with T2DM. METHODS Cross-sectional data were used of The Supplementation en Vitamines et Mineraux Antioxydants 2 (SUVIMAX2) Study (n = 284/62.2 years/48.6% women/0% T2DM (by design)) and The Maastricht Study (n = 737/59.7 years/45.2% women/28.8% T2DM (by design)). Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). Skin capillaroscopy was used to determine capillary density at baseline, and during reactive hyperemia and venous congestion. Laser Doppler flowmetry was used to assess acetylcholine-and local heating-induced vasoreactivity, and skin flowmotion. RESULTS In The SUVIMAX2 Study, cfPWV (per + 1 SD) was not associated with baseline capillary density (regression coefficient: -0.48 (95% confidence interval: 2.37; 1.41)) or capillary recruitment during venous congestion (0.54% (-0.74; 1.81%)). In addition, cfPWV was not associated with acetylcholine (-0.02% (-0.14; 0.10%)) or local heating-induced vasoreactivity (0.03% (-0.07; 0.12%)). In The Maastricht Study, in individuals without T2DM, cfPWV was not associated with baseline capillary density (-1.20 (-3.17; 0.77)), and capillary recruitment during reactive hyperemia (1.22% (-0.41; 2.84%)) or venous congestion (1.50% (-0.25; 3.25%)). In addition, cfPWV was not associated with flowmotion (-0.01 (-0.07; 0.06)). Results were adjusted for age and sex. Additional adjustments for confounders did not materially change these results. Results were qualitatively similar in individuals with T2DM. CONCLUSIONS Arterial stiffness is not associated with skin microvascular function, irrespective of the presence of T2DM.

This study sought to investigate the association of local and segmental arterial stiffness with incident cardiovascular events and all-cause mortality.The association of different stiffness indices, in particular of carotid, brachial, and femoral stiffness, with cardiovascular disease and mortality is currently unknown.In a population-based cohort (n = 579, mean age 67 years, 50% women, 23% with type 2 diabetes [by design]), we assessed local stiffness of carotid, femoral, and brachial arteries (by ultrasonography), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index, and systemic arterial compliance.After a median follow-up of 7.6 years, 130 participants had a cardiovascular event and 96 had died. The hazard ratios (HRs) (95% confidence intervals [CIs]) per 1 SD for cardiovascular events and all-cause mortality, respectively, were HR: 1.22 (95% CI: 0.95 to 1.56) and 1.51 (95% CI: 1.11 to 2.06) for lower carotid distensibility; HR: 1.19 (95% CI: 1.00 to 1.41) and 1.28 (95% CI: 1.07 to 1.53) for higher carotid elastic modulus; HR: 1.08 (95% CI: 0.88 to 1.31) and 1.43 (95% CI: 1.10 to 1.86) for lower carotid compliance; HR: 1.39 (95% CI: 1.06 to 1.83) and 1.27 (95% CI: 0.90 to 1.79) for lower femoral distensibility; HR: 1.25 (95% CI: 0.96 to 1.63) and 1.47 (95% CI: 1.01 to 2.13) for lower femoral compliance; and HR: 1.56 (95% CI: 1.23 to 1.98) and 1.13 (95% CI: 0.83 to 1.54) for higher cfPWV. These results were adjusted for age, sex, mean arterial pressure, and cardiovascular risk factors. Mutual adjustments for each of the other stiffness indices did not materially change these results. Brachial stiffness, augmentation index, and systemic arterial compliance were not associated with cardiovascular events or mortality.Carotid and femoral stiffness indices are independently associated with incident cardiovascular events and all-cause mortality. The strength of these associations with events may differ per stiffness parameter.

Advanced glycation endproducts (AGEs) are hypothesized to play a role in the development of hypertension and arterial stiffness in people with type 2 diabetes mellitus (T2DM).

In the pathogenesis of cardiovascular events, interaction between risk factors has seldom been identified. However, endothelial dysfunction on the one hand and type 2 diabetes mellitus, impaired glucose metabolism (IGM), and insulin resistance on the other may act synergistically (ie, interact) in the development of cardiovascular disease. We therefore investigated the interaction between endothelial dysfunction and type 2 diabetes mellitus, IGM, and insulin resistance with regard to risk of cardiovascular events. In a prospective population-based cohort (n=445; 69 years; 55% women; 23% type 2 diabetes mellitus, 28% IGM [by design]), endothelial dysfunction (brachial artery flow-mediated dilatation), glucose tolerance (oral glucose tolerance test), and insulin sensitivity (homeostasis model assessment for insulin resistance [HOMA2-IR]) were determined. After a median follow-up of 7.6 years, 106 participants had had a cardiovascular event. After adjustments, 1 SD less flow-mediated dilatation was associated with cardiovascular events in type 2 diabetes mellitus (hazard ratio 1.69 [95% confidence interval, 1.14–2.52]) and IGM (1.50 [0.95–2.37]) and among those in the highest HOMA2-IR tertile (1.92 [1.42–2.60]), but not in normal glucose metabolism (0.85 [0.63–1.16]) or among those in the lower 2 HOMA2-IR tertiles combined (0.85 [0.65–1.12]). Interaction between flow-mediated dilatation and type 2 diabetes mellitus, IGM, or insulin resistance was present on an additive (relative excess risk caused by interaction >0) and on a multiplicative scale ( P interaction

Advanced glycation endproducts (AGEs) are thought to play a role in the development of cardiovascular disease (CVD), especially among individuals with T2DM. Certain AGEs, like pentosidine, form cross-links between proteins within the arterial wall, which may lead to arterial stiffening, and subsequently, an increased CVD risk.

Background and aims There is increasing evidence linking arterial (mainly aortic) stiffness and type 2 diabetes, a risk factor for arterial stiffness, to cognitive impairment and dementia. However, data on carotid stiffness, which may be especially relevant for cognitive performance, are scarce, and few studies have addressed the interplay between arterial stiffness, type 2 diabetes, and cognitive performance. Methods We studied individuals with (n = 197) and without (n = 528) type 2 diabetes, who completed a neuropsychological test battery and underwent applanation tonometry and vascular ultrasound to evaluate aortic (i.e. carotid-to-femoral pulse wave velocity) and carotid stiffness (i.e. distensibility, compliance and Young's elastic modulus). Linear regression analyses were performed and adjusted for demographics, vascular risk factors, and depression. Results Overall, our results showed that carotid, but not aortic, stiffness was associated with worse cognitive performance, primarily in the domains of processing speed (standardized regression coefficient for distensibility −0.083, p = 0.040; compliance −0.077, p = 0.032) and executive function and attention (distensibility −0.133, p = 0.001; compliance −0.090, p = 0.015; Young's elastic modulus −0.081, p = 0.027). These associations did not differ by diabetes status. The differences in cognitive performance between individuals with and without type 2 diabetes (mean difference in domain scores relative to those without diabetes for free recall memory −0.23, processing speed −0.19, executive function and attention −0.23; all p ≤ 0.009 and adjusted for demographics, traditional vascular risk factors, and depression) were not substantially altered after additional adjustment for carotid stiffness. Conclusions Our findings suggest that carotid stiffness is associated with cognitive performance in both individuals with and without diabetes, but does not mediate the relationship between type 2 diabetes and cognitive dysfunction.