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The cardiovascular robustness hypothesis: Unmasking young adults' hidden risk for premature cardiovascular death
Lutz E Kraushaar1, Alexander Dressel2
1adiphea Alliance for Disease Prevention & Healthy Aging GmbH, Bad Nauheim, Germany.
Insights
Cardiovascular disease (CVD) risk prediction can be improved by assessing vascular robustness, not just risk factors. A new robustness score, derived from cardiovascular function, offers a novel way to stratify risk and enhance CVD prevention strategies.
Area of Science:
- Cardiovascular Science
- Systems Biology
- Biomedical Engineering
Background:
- Current cardiovascular disease (CVD) prevention faces challenges in identifying high-risk individuals with low-to-moderate risk factor levels.
- Conventional risk factor models may not fully capture an individual's susceptibility to CVD due to variations in vascular health.
- Aging-associated degeneration of arterial hemodynamics impacts biomarker-mortality associations, necessitating advanced risk stratification methods.
Purpose of the Study:
- To introduce and hypothesize the utility of a vascular robustness score as a novel cardiovascular risk stratifier.
- To complement existing CVD risk factor models by incorporating the vasculature's resilience against risk factor load.
- To propose a method for validating this robustness score against time-to-event data and outline a study design for hypothesis testing.
Main Methods:
- Development of a robustness score based on physical parameters quantifying cardiovascular function, inspired by systems biology principles.
- Utilization of the VascAssist 2 system, employing an electronic-hydraulic analogy to model arterial tree hemodynamics non-invasively.
- Derivation of functional parameters from pulse pressure waves and expression of the robustness score as a correction factor to calendar age (CA).
Main Results:
- Hypothesized that individuals with low robustness scores facing risk factor challenges will have higher mortality, leading to a significant robustness-CA correlation in this subgroup.
- The robustness score is conceptualized to identify individuals at high risk of premature death from CVD, even with seemingly low conventional risk factors.
- Proposed a cross-sectional study design to test the hypothesis that low robustness leads to preferential elimination in risk-factor-challenged populations.
Conclusions:
- Vascular robustness is proposed as a critical, complementary factor in cardiovascular risk prediction beyond traditional risk factors.
- The novel robustness score, derived from functional cardiovascular parameters, offers a promising new tool for enhancing CVD prevention.
- Further validation studies are encouraged to confirm the predictive power of the robustness score in diverse populations.
Abstract:
An undetected high risk for premature death of cardiovascular disease (CVD) among individuals with low-to-moderate risk factor levels is an acknowledged obstacle to CVD prevention. In this paper, we present the hypothesis that the vasculature's robustness against risk factor load will complement conventional risk factor models as a novel stratifier of risk. Figuratively speaking, mortality risk prediction without robustness scoring is akin to predicting the breaking risk of a lake's ice sheet considering load only while disregarding the sheet's bearing strength. Taking the cue from systems biology, which defines robustness as the ability to maintain function against internal and external challenges, we develop a robustness score from the physical parameters that comprehensively quantitate cardiovascular function. We derive the functional parameters using a recently introduced novel system, VascAssist 2 (iSYMED GmbH, Butzbach, Germany). VascAssist 2 (VA) applies the electronic-hydraulic analogy to a digital model of the arterial tree, replicating non-invasively acquired pule pressure waves by modulating the electronic equivalents of the physical parameters that describe in vivo arterial hemodynamics. As the latter is also subject to aging-associated degeneration which (a) progresses at inter-individually different rates, and which (b) affects the biomarker-mortality association, we express the robustness score as a correction factor to calendar age (CA), the dominant risk factor in all CVD risk factor models. We then propose a method for the validation of the score against known time-to-event data in reference populations. Our conceptualization of robustness implies that risk factor-challenged individuals with low robustness scores will face preferential elimination from the population resulting in a significant robustness-CA correlation in this strata absent in the unchallenged stratum. Hence, we also present an outline of a cross-sectional study design suitable to test this hypothesis. We finally discuss the objections that may validly be raised against our robustness hypothesis, and how available evidence encourages us to refute these objections.