Global Cardiovascular Risk Profile and Cerebrovascular Abnormalities in Presymptomatic Individuals with CADASIL or Autosomal Dominant Alzheimer’s Disease

Background: Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer’s disease and vascular dementia. Objective: Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer’s disease and vascular dementia. Methods: We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer’s disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score. Results: In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (B = –0.06, p < 0.05) and an increased severity of cerebral microbleeds (B = 0.13, p < 0.001), lacunes (B = 0.30, p < 0.001), and perivascular space enlargement in the basal ganglia (B = 0.50, p < 0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (B = 0.06, p < 0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD. Conclusion: Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks.

Effectiveness of an Intervention Aimed at Improving Information for Patients with High Cardiovascular Risk: INFORISK Clinical Trial

Background: The concept of global cardiovascular risk is not usually well understood by patients in consultation. Methods: This was a multicenter, prospective, randomized, open clinical trial of one-year duration to evaluate the effectiveness in reducing global cardiovascular risk with an intervention aimed at high-risk patients to improve information on the cardiovascular risk compared to the usual care. The intervention was focused on providing information about cardiovascular risk in a more understandable way, explaining the best practices to reduce cardiovascular risk, and tailoring information to the individual. Results: Four-hundred and sixty-four subjects participated in the study; 59.3% were men, and the mean age was 61.0 (SD 8.0) years. Significant reductions in systolic blood pressure (SBP) (−3.12 mmHg), body mass index (BMI) (−0.34 kg/m2), abdominal circumference (−1.24 cm), and REGICOR cardiovascular risk (−0.63) were observed in the intervention group. Overall, no differences in cardiovascular risk score were observed between groups at the end of follow-up. Conclusions: Providing an easy-to-understand assessment of the cardiovascular risk motivated high-risk patients to adopt a healthier lifestyle and improved cardiovascular risk after one year in the intervention group. Clinicians should assess a patient’s baseline understanding of their CV risk using tools other than absolute risk before making treatment recommendations.

P635The addition of yoga to aerobic exercise programs reduces global cardiovascular risk

Introduction Regular physical activity may modulate the inflammatory process and be cardio-protective. Yoga is a form of exercise that may have cardiovascular benefits. The effects of yoga on global cardiovascular risk have not been adequately described. The purpose of this study is to determine whether the addition of yoga to a regular exercise regimen reduces global cardiovascular risk. Methods Sixty consecutive individuals with essential hypertension were recruited in a lifestyle intervention program. All individuals with known hypertensive end organ damage, known cardiovascular diseases, as well as those taking medications/supplements that affected blood pressure, blood sugar, cholesterol or vascular inflammation were excluded. Participants were randomized to either a yoga group or similar duration stretching control group. Participants, over the 3-month intervention regimen, performed 15 minutes of either yoga or stretching in addition to 30 minutes of aerobic exercises thrice weekly. Blood pressure, cholesterol levels and hs-CRP were measured, and Reynold's Global Cardiovascular Risk Score was calculated at baseline and at the end of the 3-month intervention program. Results At screening, there were no statistically significant differences between the groups in any measured parameters or the 10-year risk of a cardiovascular event as measured by the Reynolds Risk Score. (8.2 vs. 9.0%; yoga vs. control group) After the 3-month intervention period, there was a statistically significantly greater decrease in the Reynold's Risk Score in the yoga vs. the control group. (7.0 vs. 8.4%, p=0.003, relative reduction 13.2 vs. 6.5%, p<0.0001) Baseline and 3 Month Outcomes Conclusions In patients with essential hypertension on no medications and with no known end organ damage, the practice of yoga incorporated into a 3-month exercise intervention program was associated with significant greater improvement in the Reynold's Risk of a 10-year cardiovascular event, when compared to the control stretching group. If these results are validated in more diverse populations over a longer duration of follow up, yoga may represent an important addition to traditional cardiovascular disease prevention programs.

4-Pyridoxic Acid/Pyridoxine Ratio in Patients with Type 2 Diabetes is Related to Global Cardiovascular Risk Scores

Background: Vascular diseases are multifactorial and several risk factors may have synergetic effect on the global vascular risk. Among patients with diabetes, we investigated whether vitamin B6 species differ according to global cardiovascular risk. Methods: The present observational study included 122 patients with type 2 diabetes (mean (SD) age = 69.9 (9.1) years; 50% men). Concentrations of vitamin B6 vitamers were measured. Classical blood biomarkers and risk factors were used to compute a multivariate risk score. Results: Plasma concentrations of 4-pyridoxic acid were higher in patients with high risk versus those with low risk scores (48.2 (63.7) vs. 31.9 (15.0) nmol/L; p = 0.031). Plasma pyridoxine was significantly lowered in patients at high risk (2.8 (28.4) vs. 38.1 (127.8) nmol/L; p = 0.003). PAr index (4-pyridoxic acid/pyridoxal + pyridoxal 5′-phosphate) (1.05 (0.07) vs. 0.84 (0.06); p = 0.017) and the ratio of 4-pyridoxic acid/pyridoxine (7.0 (4.8) vs. 3.9 (3.2); p < 0.001) were higher in patients at high risk. After adjustment for cystatin C and C-reactive protein, only pyridoxine and 4-pyridoxic acid/pyridoxine ratio remained significantly different according to vascular risk scores. 4-Pyridoxic acid/pyridoxine ratio was the best marker to discriminate between patients according to their risk scores—area under the curve (AUC) (95% confidence intervals (CI)) = 0.72 (0.62–0.81). 4-Pyridoxic acid/pyridoxine ratio was directly related to plasma levels of soluble vascular cell adhesion molecule 1. Conclusion: Vitamin B6 metabolism was shifted in patients with multiple vascular risk factors. The catabolism to 4-pyridoxic acid was enhanced, whereas the catabolism to pyridoxine was lowered. High 4-Pyridoxic acid/pyridoxine ratio is independently associated with global cardiovascular risk.