This study indicated that cognitive decline is a common adverse consequence after CVS. Better knowledge of the riskfactors for PSD should increase the effectiveness of preventive strategies for patients with stroke. A signiﬁ cant inverse relationship was identiﬁ ed between Hcy and cogni- tion despite the presence of other relevant riskfactors for stroke. It is possible that cognitive impairment may result from CVS and its related vascularriskfactors including the direct association with high Hcy levels. Longer follow up studies in large sample size are necessary to determine the impact of Hcy on progression of post-stroke cognitive impairment. Because HHcy is a potentially reversible risk factor and can be identiﬁ ed early, prospective intervention studies should investigate whether lowering Hcy levels by vitamin supplementations could reduce the incidence and progression of cognitive decline after stroke.
Abstract The objective was to evaluate the presence of a positive family history (FH) of vascularriskfactors between patients with migraine with aura (MA) and migraine without aura (MO), and in chronic migraine (CM) compared to other headache types. As migraine patients are typically too young to have developed vascular events, studying older relatives of migraine patients may be a practical means of evaluating associations between vascularriskfactors and migraine. A cross-sectional study of a clinic- based sample of adults with migraine headache was carried out at the University of Utah. Predictor variables comprised first or second degree relatives with stroke, hyper- tension, diabetes or hypercholes- terolaemia. Outcome measures comprised diagnosis of MA, MO or CM according to the revised International Headache Society cri- teria. There was no significant dif- ference in FH of vascularrisk fac- tors in MA compared to MO (adjusted OR 1.04, 95% CI 0.61–1.78). CM was associated with a decreased risk of FH of stroke (OR=0.11, 95% CI
incident dementia; ﬁ rst for VaD, but also for AD + VaD, and to a lesser extent for AD alone. When relative risk was reported by subgroup, the strength of association diminished in the following order: VaD > AD + VaD > AD (ﬁ ve of ﬁ ve studies for diabetes mellitus; four of four studies for HTN; one study for high cholesterol and one study of aggregate risk). Th e trends across dementia sub- groups is consistent with the hypothesis that vascularriskfactors increase atherosclerosis, which promotes subclinical vascular brain injury that exerts an additive eﬀ ect with AD pathology to symptomatically unmask dementia. Th ese data cannot prove or disprove the alter- native hypothesis that vascularriskfactors or athero- sclerosis increase AD pathology. Th e advent of biochemi- cal markers for AD (for example, amyloid imaging and cerebrospinal ﬂ uid Aβ and phospho-tau) may allow this question to be revisited in the future with improved speciﬁ city for the diagnosis of AD in clinical settings.
I hereby solemnly declare that this dissertation titled “Effects Of Longterm Antiepileptic Drugs On VascularRiskFactors And Atherosclerosis” was done by me in Institute of Neurology, Madras Medical college and Rajiv Gandhi Government General Hospital, Chennai -3, under the guidance and supervision of Prof. Dr. S. Balasubramanian.MD., D.M., Professor of Neurology, Institute of Neurology, Madras Medical College & Rajiv Gandhi Government General Hospital, Chennai. This dissertation is submitted to the Tamil Nadu Dr. M.G.R. Medical University towards the partial fulfillment of requirement for the award of D.M Degree Branch I (NEUROLOGY).
They were subsequently followed up at age 8 years as part of an ongoing lon- gitudinal cohort consisting of the original randomized trial participants. Vascularriskfactors and carotid IMT were assessed only at the 8-year visit. We have previously shown that these trial interventions did not alter any vascularriskfactors or body size measurements in these children. 12 Two
earlier at approximately age 69 was very similar; our “history of hypertension” captured prior hypertension and was the strongest risk factor. Age 72 is not par- ticularly “old.” The stroke cohort including much younger subjects produced the same result. Future studies could test other BP parameters. Adding other imaging markers of SVD might increase the sensitiv- ity for detecting causal relationships. Some variables were missing but without evidence of bias and we used all available data. The high prevalence of peri- pheral vascular disease in the LBC1936 may represent overreporting but is counterbalanced by the objective measure of peripheral vascular disease with the ABPI and by the MSS where history and examination were very detailed and the same associations were found.
One might expect the magnitude of benefit would be no greater than that seen in secondary prevention of car- diovascular disease including stroke. If that is the case, there needs to be a paradigm shift in clinical trials ad- dressing this issue. Much larger sample sizes are re- quired, in the thousands or even tens of thousands as have been recruited to cardiovascular trials, and the dur- ation of follow-up needs to be a number of years. Several cardiovascular trials, such as for statin therapy , have not shown separation between the treatment and pla- cebo arms until after one year. Because the timescale to show benefit is likely to be a few years, it may be most practical to perform trials in patients with early AD. One potentially attractive option would be to perform trials using a VRF package including treatment of com- mon riskfactors such as hypertension, DM, hypercholes- terolaemia and smoking cessation.
Abstract: Despite the fact that vascular dementia (VaD) represents the seconding leading cause of dementia in the USA, behind only Alzheimer’s disease (AD), there remains a lack of consensus on the pathological criteria required for diagnosis of this disease. A number of clinical diagnostic criteria exist but are poorly validated and inconsistently applied. It is clear that vascularriskfactors play an important role in the etiology of VaD, including hypertension, stroke, diabetes, and atherosclerosis. Vascularriskfactors may increase the risk for VaD by promoting inflammation, cerebral vascular disease, white matter lesions, and hippocampal sclerosis. Because vascularriskfactors seem to impart a high degree of risk for conferring VaD, it seems logical that the apolipoprotein E (APOE) status of individuals may be important. APOE plays a critical role in transporting cholesterol in and out of the CNS and in AD it is known that harboring the APOE allele increases the risk of AD perhaps due to the improper functioning of this protein. The purpose of this review is to examine the important pathological features and riskfactors for VaD and to provide a critical assessment of the current literature regarding whether or not apoE4 also confers disease risk in VaD. The preponderance of data suggests that harboring one or both APOE4 alleles elevates the risk for VaD, but not to the same extent as found in AD.
In summary, to make a diagnosis of TGA, all strict clinical criteria as shown in Table 1 should be met. The differential diagnosis includes structural (vascular) disease, epileptic amnesia, delirium, intoxication, and head injury and migraine headaches. When a general physician is presented with a typical case, no additional diagnostic tests, such as MRI and EEG, are needed. This even holds when such a patient has vascularriskfactors. However, when focal neurological signs accompany anterograde amnesia, neuroimaging is warranted and potentially a neurology consult. If retrograde amnesia is also affected and emotional distress is present, the clinician needs to consider psychogenic amnesia. Alternatively, albeit rare but more ominous, are those cases of “painless” aortic dissection, where TGA is the primary symptom as chest pain is lacking. Finally, research findings using DWI–MRI support the concept of focal ischemia. These focal lesions have a maximum detectability between 48 and 72 hours after the start of TGA. Focal lesions have been demonstrated in the
tions between adjusted cognitive scores and Framingham risk scores were assessed using the Pearson product–moment correla- tion coefficient. The risk of incident cardiovascular events associ- ated with quartile of adjusted cognitive test scores was studied using Cox proportional hazards analysis to estimate hazard ratios (HRs) with 95% CIs. Linear trend by quartile was assessed using a likelihood ratio test. The time to an event was defined as the time from completion of cognitive testing to the occurrence of an adjudicated MI, stroke, or CHD death. Participants were censored from the analysis at death, study dropout, or at the time of final contact. All multivariable models included terms for the following covariates unless otherwise noted: age, race (nonwhite vs white), gender, and education (at least some college, high school, or voca- tional school vs incomplete high school). We decided a priori to include demographic factors in the multivariable models to reduce the risk of residual confounding and to provide an estimate of the association of O/E ratios with cardiovascular disease that was independent of demographic characteristics. Covariates for the following vascularriskfactors were entered and remained in mod- els as a single group: hypertension, diabetes, current smoking status, LDL and HDL cholesterol, and LVH on EKG. The propor- tional hazards assumption was examined using both graphical and analytical methods and was adequately met. 20 We also per-
The resulting MRI was interpreted by trained readers at the ARIC MRI Reading Center at Johns Hopkins Medical Institutions in Baltimore, MD. Images were interpreted directly from a PDS-4 digital workstation consisting of four 1024 ⫻ 1024-pixel monitors capable of displaying all 96 images simultaneously. Each study had a primary and secondary interpretation rendered by different readers. All studies were assessed without knowledge of partici- pants’ age, gender, race, previous imaging findings, or vascularriskfactors. All primary readers were board-certified radiologists with subspecialty training in neuroradiology. Secondary readers included the same radiologists plus an experienced neuroimaging technician.
Recent work has identiﬁ ed at least two lineages of pro- inﬂ ammatory T cells contributing to GCA; Th 1 and Th 17 cells. It is currently unknown whether the process of immunosenescence aﬀ ects Th 1 and Th 17 cells in a lineage-speciﬁ c way or whether both T-cell types age in parallel. Th e molecular details of T-cell aging in GCA remain to be elucidated. In GCA patients, Th 1 and Th 17 cells diﬀ er in therapeutic responsiveness and participa- tion in early and chronic disease. Evidence suggests that the two lineages respond to distinct instigators. A combination of pathogen-derived and tissue-indigenous danger signals may result in the chronic granulomatous inﬂ ammation that characterizes GCA. Th erapeutic approaches for GCA patients need to be tailored to the special needs of the aging host. Immunosuppression needs to be restricted to avoid further weakening of immunocompetence. DCs originate from the bone marrow and the development of DC-target therapies will require a much better understanding of their life cycle. Enhancing immune cell regeneration could help in clearing chronic infections. Prevention of vascular aging is a long-drawn process that should begin during middle age. Given similarities in the inﬂ ammatory process that typiﬁ es atherosclerosis and GCA, it is possible that managing standard vascularriskfactors could function as adjuvant therapy in the treatment of large vessel vasculitis.
The median follow-up time was 42 days [IQR 35–49], providing 6493 patient-days of data. One hundred and three (62.8%) patients were cured at discharge at the end of our observation period. Twenty-nine patients (17.7%) experienced severe COVID-19 illness with a median (14 [7–27] days) duration between symptom onset to devel- oping a severe disease, an event rate of 4.47 per 1000- patient days (95%CI 3.10–6.43). Six patients (3.7%) died during hospitalization, an event rate of 0.84 per 1000- patient days (95%CI 0.38–1.88). Kaplan-Meier curves showed that the risk of severe COVID-19 illness tended to increase with the number of vascularriskfactors (log rank P < 0.001, Fig. 1). In univariable analysis, the risk of severe COVID-19 increased with increasing vascularrisk factor burden (unadjusted HR 2.06, 95%CI 1.51–2.80). After adjustment for age and sex, the vascularrisk factor burden remained significantly associated with severe COVID-19. (adjusted OR 1.55 95%CI 1.09–2.21, Table 3). This relationship did not change after additional con- founder adjustment for, separately, COPD, cardio- cerebrovascular disease, tumor and renal impairment, in addition to age and sex (Table S1). Separate adjustment for routine blood examinations and chest CT findings, in addition to age and sex, did not alter our results (Table S2). Sensitivity analyses revealed that it would need moderately robust unobserved confounding to ren- der the exposure-outcome association null. (Table 3, Table S1 and Table S2). For example, an E-value of 2.12 for the estimate (Table 3, and Figure S1) indicates that the observed risk ratio of 2.12 could only be explained away by an unmeasured confounder that was associated with both the exposure and the outcome by risk ratios of more than two, above and beyond the measured con- founders, but weaker confounding could not do so .
and most of the principal cardiovascular riskfactors, such as hypertension, hyperlipidemia, overweight and obesity, meta bolic syndrome, smoking, and sedentary lifestyles. Moreover, ED is an independent risk factor for the new onset of CVD, and it is an important predictor of the devel- opment of major cardiovascular events in diabetic patients with known CAD. The debate as to whether FSD should be classified as a dysfunction similar to ED or whether it should be considered a pathologic condition at all is not ended. Although diabetic women suffer from the same neurovas- cular complications that contribute to the pathogenesis of ED in men, results of sexual functioning of diabetic women are less conclusive. However, a high prevalence of FSD has been described in both type 1 and type 2 diabetic women as compared with non-diabetic women, with most studies reporting psychosocial issues as a main determinant of FSD. Although ED in men has been recognized as a powerful predictor of major cardiovascular events, it is still not clear whether FSD may be indicated as a risk factor for CVD. Based on the current limited data, it seems as though an association between female sexual health and vascularriskfactors (hypertension, hyperlipidemia, metabolic syndrome/ obesity, diabetes, and CAD) exists; however, at the present time, there are no data supporting the idea that FSD can be indicated as a predictor of future cardiovascular events. 25 The
score. Thus, our clustering mecha- nism is not inclusive of all known car- diovascular risks. Inﬂammatory mark- ers were omitted because they were not used in the PDAY score and are in- frequently measured in pediatric pa- tients. Smoking also was omitted from our clustering score because there were only 11 smokers in our popula- tion. Second, we found that in youth with 2 or more cardiovascular risk fac- tors, higher carotid vascular thickness and stiffness compared with those with 0 to 1 risk factor. To date, normal values for this age group have not been established. Therefore, we can not say whether there are no vascular changes in the low-risk group. Finally, our cross-sectional design does not al- low us detect when changes occur in the vasculature in relation to the devel- opment to riskfactors. Similarly, we can not prove that increased cardio- vascularriskfactors lead to vascula- ture changes. Longitudinal evaluation is needed to make these conclusions.
performed during the initial workup directly after the index stroke. Due to our longer follow-up, patients were older at the time of the MRI scan and had a higher prevalence of vascularriskfactors. In addition, WMHs in those studies was only rated by the Fazekas score and not quantitative. Due to the combination of a high prevalence of vascularriskfactors and long follow-up duration, patients may have been exposed to those riskfactors for a longer period. However, 10 years after the stroke, patients in our study still were young and had a mean age of only 49.8 years and the prevalence of vascularriskfactors was identical in our controls.
All patients were screened for type 2 Diabetes Mellitus and its complications. Each subject’s details regarding riskfactors like age, sex, Duration of Diabetes, B.M.I, socioeconomic status, family history, History of hypertension, Fasting Blood Sugar level, postprandial blood sugar level ,Systolic and diastolic blood pressure medical adherence and exercise and diet control is collected for all the patients. For measuring medical adherence Morisky Medication Adherence (MMAS-4) scale is used. The selected patients were observed for presence of vascular (micro and macro) complications who had undergone the test for Retinopathy by fundus examination, Nephropathy by micro albuminuria, serum creatinine and blood urea, Neuropathy by history of numbness paraesthesia, tingling sensation, burning sensation and confirmed by touch sensation 1 ,
Coagulase-negative staphylococci are the most common cause of central line – associated bloodstream infections in the United States. Therefore, the use of low-dose vancomycin in parenteral ali- mentation solutions (at concentrations above the minimal inhibitory concen- tration) has been suggested as a way to decrease the incidence of bacter- emia attributable to coagulase-negative staphylococci. Five randomized clinical trials of low-dose vancomycin in pre- term neonates have been conducted, all of which date from the late 1990s. In 4 of the studies, there was a statistically signi ﬁ cant reduction in the incidence of coagulase-negative staphylococcal sepsis (relative risk [RR], 0.11; 95% con ﬁ dence interval [CI], 0.05 – 0.24) 28 ;
The association of LFP with the metabolic syndrome is a clinically-significant one since the metabolic syndrome in patients with established vascular disease identifies a cohort at an increased risk of cardiovascular events [1-4]. Indeed, liver fat percent has been shown to be greater in obese insulin-resistant patients vs obese insulin-sensitive patients (10.5% vs 5.6%) with the obese insulin-sensitive patients having a carotid intima-media thickness compa- rable to healthy normal weight individuals . Hence, while the definition of obesity has evolved from weight to body mass index and more recently waist circumference and subsequently visceral fat area, liver fat percent may represent the future determinant of obesity-related car- diovascular risk assessment. Indeed, it is possible that obese patient with higher amount of visceral fat area but low liver fat percent may have a cardiovascular event rate comparable to normal-weight individuals. While our data are encouraging in showing that liver fat percent may bet- ter identify the at-risk patient than visceral fat area, our data set is small and cross-sectional. A large prospective cohort is required to determine if liver fat percent is inde- pendently associated with cardiovascular events. One limitation of this test is the availability of MRI; however, from a pragmatic perspective, such a measure would be preferable to visceral fat area since liver fat percent is eas- ier to measure and does not require tracing of fat areas on abdominal MRI slices. Further, it would be valuable to validate liver fat percent as a measure of obesity-related cardiovascular risk in various ethnic groups since Asians, in particular, are prone to cardiovascular disease and dia- betes at lower waist circumference or body mass index than Europids [17,18]. In summary, we have shown liver fat percent to be associated with the metabolic syndrome independently of visceral fat area. Our results suggest that this measure requires further validation as a maker of obesity-related cardiovascular risk and assessment in prospective cohort studies.
h. Loss of visual acuity: Microaneurysms, abnormalities of the veins, and small blot haemorrhages and exudates situated in the periphery will not interfere with vision unless they are associated with oedema and thickening in the macular area. Macular oedema should be suspected if there is impairment of visual acuity, even if this is associated with only mild peripheral non-proliferative retinopathy and no other obvious pathology. Macular oedema can only be confirmed or excluded on slit lamp retinal bio microscopy. If macular changes are observed by direct ophthalmoscopy or retinal photography, referable maculopathy should be suspected. Sudden visual loss occurs with vitreous haemorrhage or retinal detachment. In pre-proliferative and proliferative retinopathy, whether or not visual acuity is impaired, prompt laser treatment is important to reduce the risk of haemorrhage, fibrosis/gliosis and severe irreversible visual impairment.