Scharf, Eugene L

Objective: This single-arm, pre–post interventional trial (clinicaltrials.gov, NCT04515095) investigates the safety, feasibility, and potential effectiveness of prolonged water-only fasting followed by a whole-plant-food diet in the long-term management of hypertension and other cardiometabolic disorders. Methods: Safety was assessed based on adverse events (AEs) that were recorded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Feasibility was assessed based on retention rate, ability to complete minimal fast length, and intervention acceptability. Twenty-nine participants with stage 1 and 2 hypertension and without type 2 diabetes were enrolled from a residential fasting center. Results: Study retention was 100% at the end of the refeed and 93% at the six-week follow-up visit. Median (range) fasting and refeeding duration were 11 (7–40) and 5 (3–17) days, respectively, and 90% of participants were able to complete at least 7 days of fasting. The majority of AEs were mild (grade 1) and transient and there were no higher-grade or serious AEs. At the end of the intervention, median systolic/diastolic blood pressure had normalized to below 130/80 mmHg, body weight reduced by >5%, and anti-hypertensive medication was completely discontinued. These results were sustained for at least six weeks and potentially up to one year. Conclusions: Our data suggest that the intervention may be a feasible, well-tolerated, low-risk option for lowering and managing high blood pressure, excess body weight, and other cardiometabolic disorders in people with stage 1 and 2 hypertension.

(1) Background: Chronic inflammation and insulin resistance are associated with cardiometabolic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Therapeutic water-only fasting and whole-plant-food refeeding was previously shown to improve markers of cardiometabolic risk and may be an effective preventative treatment but sustained outcomes are unknown. We conducted a single-arm, open-label, observational study with a six-week post-treatment follow-up visit to assess the effects of water-only fasting and refeeding on markers of cardiometabolic risk. (2) Methods: Patients who had voluntarily elected and were approved to complete a water-only fast were recruited from a single-center residential medical facility. The primary endpoint was to describe changes to Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores between the end-of-refeed visit and the six-week follow-up visit. Additionally, we report on changes in anthropometric measures, blood lipids, high-sensitivity C-reactive protein (hsCRP), and fatty liver index (FLI). Observations were made at baseline, end-of-fast (EOF), end-of-refeed (EOR), and six-week follow-up (FU). (3) Results: The study enrolled 40 overweight/obese non-diabetic participants, of which 33 completed the full study protocol. Median fasting, refeeding, and follow-up lengths were 14, 6, and 45 days, respectively. At the FU visit, body weight (BW), body mass index (BMI), abdominal circumference (AC), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein (LDL), hsCRP, and FLI were significantly decreased from baseline. Triglycerides (TG) and HOMA-IR scores, which had increased at EOR, returned to baseline values at the FU visit. (4) Conclusion: Water-only fasting and whole-plant-food refeeding demonstrate potential for long-term improvements in markers of cardiovascular risk including BW, BMI, AC, SBP, DBP, blood lipids, FLI, and hsCRP.

(1) Background: Cardiometabolic disease, including insulin resistance, hyperlipidemia, and hypertension, are major contributors to adverse health outcomes. Fasting has gained interest as a nonpharmacological therapeutic adjunct for these disorders. (2) Methods: We conducted a prospective, single-center study on the effects of prolonged water-only fasting followed by an exclusively whole-plant-food refeeding diet on accepted measures of cardiovascular risk and metabolic health. Participants were recruited from patients who had voluntarily elected to complete a water-only fast in order to improve their overall health according to an established protocol at an independent, residential medical center. Median fasting and refeed lengths were 17 and 8 days, respectively. The primary endpoint was to describe the mean glucose tolerance as indicated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores at baseline, end-of-fast (EOF), and end-of-refeed (EOR) visits. Secondary endpoints were to describe the mean weight, body mass index (BMI), abdominal circumference (AC), systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid panel, and high-sensitivity C-reactive protein (hsCRP) at the same time points. (3) Results: The study enrolled 48 overweight/obese non-diabetic participants, of which 26 completed the full study protocol. At the EOF visit, the median SBP, AC, low-density lipoprotein (LDL), and hsCRP were decreased and triglycerides (TG) and HOMA-IR scores were increased. Conclusion: Prolonged water-only fasting and whole-plant-food refeeding holds potential as a clinical therapy for cardiometabolic disease but increased TG and HOMA-IR values after refeeding necessitate further inquiry.

Background White matter hyperintensity (WMH), characterized by hyperintensities on T2‐weighted fluid‐attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS. Methods and Results We enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson r =0.24, P =0.03; >50 years, Pearson r =0.62, P <0.0001; juxtacortical WMH: ≤50 years, Pearson r =0.09, P =0.40; >50 years, Pearson r =0.55, P <0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient −0.17, P =0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow‐up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05–1.92; P =0.03). Conclusions Peripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.

Endovascular management of acute ischemic stroke secondary to septic emboli from bacterial endocarditis is case-specific and outside established guidelines. We report three new cases of an acute ischemic stroke secondary to septic embolus from two different centers. All cases reported here were large vessel occlusions of the middle cerebral artery in anticoagulated patients. In one case the embolus was noted to be firm and aspiration thrombectomy was attempted in lieu of stent retrieval. Thrombolysis in Cerebral Ischemia (TICI) 3 recanalization was achieved and the patient experienced a good outcome with resolution of deficits. In this case, pathologic analysis of the embolus was available. These additional three cases from two centers add to the small but growing literature for interventional management of acute ischemic stroke in bacterial endocarditis.