Preventing Cardiovascular Disease. Complementary precision medicine

Abstract: AbstractBackground: Non-communicable diseases are the number one killer worldwide and the leading one,cardiovascular disease (CVD), is responsible for more than 30% of all deaths. CVD is a progressive disease whichalso makes it economical, easy and effective to prevent. There are many stages of CVD that ultimately can lead tocoronary atherosclerosis, measurable as coronary artery calcification (CAC) score by cardiac computed tomography(CT). Before coronary atherosclerosis develops there are many stages of the process: inflammation, reducedendothelial function, hypertension and impaired microcirculation. Precision medicine is a popular novelty inmedicine that combines well-established results and medical history with computer science and novel biomedicalinformation.Aims: The aims of the study were: (I) to evaluate whether aged garlic extract (AGE) can influence CAC and topredict the individual effect of AGE; (II) to assess the effect of long-term treatment with AGE on cutaneous tissueperfusion; (III) to evaluate whether a daily supplement of AGE could reduce inflammation in females with low risk ofcardiovascular disease; (IV) to assess the effect of long-term treatment with AGE on peripheral tissue perfusion inpatients with confirmed atherosclerosis; and (V) to validate a prediction model to explore whether an individualpatient will have a positive effect of AGE on their CAC score and blood pressure.Methods: Studies I-IV were single-centre parallel randomised controlled studies. Patients were randomised, in adouble-blind manner, through a computer-generated randomisation chart to an intake of placebo or AGE (2400 mgdaily) for 12 months. In Study I a prediction model was developed using a cross-industry standard process for datamining and in Study V this method for developing prediction models was validated in a new cohort.The cohort usedwas pooled from previously published studies in the USA.Results: There was a significant change in CAC progression (OR: 2.95 [1.05–8.27]), in favour of the AGE group.The developed algorithm could predict with 79% precision which patient would have a more favourable effect ofAGE on CAC score. Cutaneous microcirculation was measured at 0 and 12 months and the mean post-occlusivereactive hyperaemia (PORH) differed significantly between time points. The mean percent was 102, 64 (174, 15)%change for AGE and 78, 62 (107, 92)% change for the placebo group (F[1, 120] = 5. 95, p < 0.016). Femalestreated with AGE showed lower levels of inflammatory biomarker interleukin-6 (IL-6) after 12 months of AGEtreatment. After 12 months of AGE, an increase of 21.6% (95% CI 3.2%-40.0%, p < 0.05) was seen in the relativechange of PORH. The same response was seen for CVC and acetylcholine with an increase of 21.4% (95% CI3.4%-39.4%, p < 0.05) in the AGE group. Study V demonstrated that it is possible to develop predictive models.Theconstructed algorithm was able to predict with 64% precision which patient would have a significant reduction ofCAC.Conclusion: AGE inhibits CAC progression, lowers IL-6, glucose levels and blood pressure and increases themicrocirculation in patients at increased risk of cardiovascular events. It is also possible to predict which patient willhave a more favourable effect of AGE. AGE lowers IL-6 in females with a low risk of CVD. AGE regeneratedperipheral tissue perfusion and increased microcirculation in patients with arteriosclerosis.For many patients it is essential to know if they will have an effect of a treatment before changing their daily lives.The developed algorithm shows that it is feasible to develop predictive models for answering this question.