One in every two deaths in the United States is caused by cardiovascular disease. Despite strong mechanistic links established between a diet rich in lipids and the pathogenesis of cardiovascular disease, therapeutic advances have focused on reduction in either ingestion or synthesis of cholesterol, and reduction in dietary trans and saturated fatty acids and triglycerides. Even in the setting of aggressive high potency statin therapy and global cardiovascular risk reduction efforts, most clinical trials reveal a significant residual cardiovascular risk with, at best, only 30% reduction in major adverse cardiovascular events. There exists a significant unmet clinical need for identifying novel therapies for the prevention and treatment of cardiovascular disease. This requires identification of additional contributory processes to cardiovascular disease pathogenesis, so that mechanism-based interventions may be developed. Endothelial dysfunction is a pathological state in which there is systemic inflammation of vascular endothelium with consequent expression of pro-vasoconstrictive mediators, thrombotic and atherogenic tendencies. Endothelial dysfunction precedes the development of atherosclerosis and portends an increased risk of future adverse cardiovascular events. Endothelial dysfunction, therefore, can serve as a "barometer" of future cardiovascular risk. Measurement of Flow-mediated dilation ( FMD) is widely accepted as a method to assess vascular endothelial function.

Researchers at MCW have discovered a new pathway that links the type of bacteria present in the intestines to the severity of heart attacks. This discovery of a relationship between intestinal bacteria, bacterial metabolites, and severity of heart attacks means that for the first time, we may be able to determine a person's probability of having a heart attack via non-conventional risk factors. This may provide opportunities for novel diagnostic tests as well as a potential for therapeutic intervention. The link between gut microbiota and the severity of heart attacks may also lead to novel therapeutic approaches (probiotics, non-absorbable antibiotics) to prevent heart attacks from happening. Our pilot study has demonstrated that supplementation of Lactobacillus plantarum 299v (Lp299v) for 6 weeks to adults with a history of coronary artery disease showed improvement in endothelial function. Whether acute ingestion of a single drink containing Lp299v supplementation favorably impacts vascular endothelial function is not known. The study proposed will test the hypothesis that supplementation of Lp299v favorably impacts vascular endothelial function after ingestion of a single supplement containing Lp299v.

Specific Aim 1 will determine the acute impact of probiotic supplementation on endothelial cell function as measured by brachial artery flow mediated dilation (FMD)

Specific Aim 2 will determine the impact of acute probiotic supplementation on blood biomarkers for inflammation.

Specific Aim 3 will be to determine the impact of baseline constitution of intestinal microbiota (assessed by stool microbiome) on change in FMD as a result of acute response to probiotic supplementation.

Specific Aim 4 will be to determine the impact of baseline constitution of intestinal microbiota (assessed by stool microbiome) on change in levels of blood markers for inflammation as a result of acute response probiotic supplementation.

Inclusion Criteria:

Have at least one of the following conditions:

• Hypertension
• Hyperlipidemia
• Diabetes mellitus (Type 1 or Type 2)
• Peripheral vascular disease
• Cerebrovascular disease
• Cardiovascular disease.

Exclusion Criteria:

• Unstable angina or myocardial infarction by history, ECG, and/or enzymatic criteria within 1 month of enrollment.
• LV dysfunction as defined by an LV ejection fraction documented as < 45% within 1 year of enrollment by an echocardiogram, MRI, or nuclear imaging.

Uncontrolled hypertension with blood pressure greater than 170/100 mmHg at the screening visit.

• Known history of chronic renal insufficiency, liver dysfunction, or cancer besides non-melanoma skin carcinomas or localized prostate cancer requiring systemic treatment within five years of enrollment.
• Known history of cognitive impairment or inability to follow study procedures
• Patient with an implanted defibrillator or permanent pacemaker on which the potential participant is known to rely upon for greater than 50% of ventricular depolarizations.
• Patients who received probiotics, prebiotics, and antibiotics in the last 12 weeks.
• Patients with dosing changes of vasoactive medications and HMG-CoA reductase inhibitors in the 6 weeks prior to enrollment.
• Pregnancy
• Patients who are currently taking Vitamin K antagonists such as coumadin, warfarin.
• Those who are daily drinkers.
• Patients with gastrointestinal diseases that might alter the impact of a probiotic (e.g. status post colectomy, short gut syndrome, or inflammatory bowel disease)