Preventing Cardiovascular Disease. Complementary precision medicine.

Bidragets översatta titel : Förebyggande av Hjärt- och kärlsjukdom: Komplementär precisions medicin

Martiné Wlosinska

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

113 Nedladdningar (Pure)

Sammanfattning

Abstract
Background: 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 which
also makes it economical, easy and effective to prevent. There are many stages of CVD that ultimately can lead to
coronary 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, reduced
endothelial function, hypertension and impaired microcirculation. Precision medicine is a popular novelty in
medicine that combines well-established results and medical history with computer science and novel biomedical
information.
Aims: The aims of the study were: (I) to evaluate whether aged garlic extract (AGE) can influence CAC and to
predict the individual effect of AGE; (II) to assess the effect of long-term treatment with AGE on cutaneous tissue
perfusion; (III) to evaluate whether a daily supplement of AGE could reduce inflammation in females with low risk of
cardiovascular disease; (IV) to assess the effect of long-term treatment with AGE on peripheral tissue perfusion in
patients with confirmed atherosclerosis; and (V) to validate a prediction model to explore whether an individual
patient 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 a
double-blind manner, through a computer-generated randomisation chart to an intake of placebo or AGE (2400 mg
daily) for 12 months. In Study I a prediction model was developed using a cross-industry standard process for data
mining and in Study V this method for developing prediction models was validated in a new cohort.The cohort used
was 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 of
AGE on CAC score. Cutaneous microcirculation was measured at 0 and 12 months and the mean post-occlusive
reactive 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). Females
treated with AGE showed lower levels of inflammatory biomarker interleukin-6 (IL-6) after 12 months of AGE
treatment. After 12 months of AGE, an increase of 21.6% (95% CI 3.2%-40.0%, p < 0.05) was seen in the relative
change of PORH. The same response was seen for CVC and acetylcholine with an increase of 21.4% (95% CI
3.4%-39.4%, p < 0.05) in the AGE group. Study V demonstrated that it is possible to develop predictive models.The
constructed algorithm was able to predict with 64% precision which patient would have a significant reduction of
CAC.
Conclusion: AGE inhibits CAC progression, lowers IL-6, glucose levels and blood pressure and increases the
microcirculation in patients at increased risk of cardiovascular events. It is also possible to predict which patient will
have a more favourable effect of AGE. AGE lowers IL-6 in females with a low risk of CVD. AGE regenerated
peripheral 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.
Bidragets översatta titel Förebyggande av Hjärt- och kärlsjukdom: Komplementär precisions medicin
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Institutionen för kliniska vetenskaper, Lund
Handledare
  • Lindstedt, Sandra, handledare
  • Hlebowicz, Joanna, Biträdande handledare
  • Malmsjö, Malin, Biträdande handledare
  • Algotsson, Lars, Biträdande handledare
Tilldelningsdatum2021 nov. 26
UtgivningsortLund
Förlag
ISBN (tryckt)978-91-8021-125-3
StatusPublished - 2021

Bibliografisk information

Defence details
Date: 2021-11-26
Time: 13:00
Place: Astronomihuset, Sölvegatan 27 i Lund. Join by Zoom: https://lu-se.zoom.us/j/68011044619?pwd=eVVsdGZxNmNkRzJDaUxVR1UwVWU2Zz09
External reviewer(s)
Name: Risérus, Ulf
Title: professor
Affiliation: Uppsala University

Ämnesklassifikation (UKÄ)

  • Annan klinisk medicin

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