A six question screen to facilitate primary cardiovascular disease prevention

Background: European guidelines on primary prevention of cardiovascular disease (CVD) recommend the SCORE risk charts for determining CVD risk, which include blood pressure and serum cholesterol as risk parameters. To facilitate cost-effective large-scale screening, we aimed to construct a risk score with 'non-invasive' parameters as a first screening step to identify persons at increased CVD risk requiring further risk assessment. Methods: We used data of Dutch employees from 25 organisations participating in a health risk assessment between August 2007 and January 2013. Backward multivariate logistic regression analysis was employed to select non-invasive, independent predictors of high CVD risk, defined as the 10-year risk of fatal CVD of ≥5 % based on the SCORE formula. The total CVD risk score was calculated as the summed coefficients of the retained variables. Results: Data of 6189 male participants was used for the development and validation of the risk score. Age, tobacco use, history of hypertension, alcohol consumption, BMI, and waist circumference were independent predictors of high CVD risk. Ten-fold cross-validation resulted in an area under the curve of 0.95 (SE 0.01, 95 % confidence interval 0.94-0.96). A cut-off score ≥45 on the CVD risk score yielded a sensitivity of 0.93, and a specificity of 0.85. Conclusions: We developed a simple, non-invasive risk score that accurately identifies persons at increased CVD risk according to the SCORE formula in a population of working men. The risk score enables a stepwise approach in large screening programmes, strongly reducing the number of persons that require full risk estimation including blood pressure and cholesterol measures

Sympathetic activation by lower body negative pressure decreases kidney perfusion without inducing hypoxia in healthy humans

Purpose There is ample evidence that systemic sympathetic neural activity contributes to the progression of chronic kidney disease, possibly by limiting renal blood flow and thereby inducing renal hypoxia. Up to now there have been no direct observations of this mechanism in humans. We studied the effects of systemic sympathetic activation elicited by a lower body negative pressure (LBNP) on renal blood flow (RBF) and renal oxygenation in healthy humans. Methods Eight healthy volunteers (age 19-31 years) were subjected to progressive LBNP at - 15 and - 30 mmHg, 15 min per level. Brachial artery blood pressure was monitored intermittently. RBF was measured by phase-contrast MRI in the proximal renal artery. Renal vascular resistance was calculated as the MAP divided by the RBF. Renal oxygenation (R2*) was measured for the cortex and medulla by blood oxygen level dependent (BOLD) MRI, using a monoexponential fit. Results With a LBNP of - 30 mmHg, pulse pressure decreased from 50 +/- 10 to 43 +/- 7 mmHg; MAP did not change. RBF decreased from 1152 +/- 80 to 1038 +/- 83 mL/min to 950 +/- 67 mL/min at - 30 mmHg LBNP (p = 0.013). Heart rate and renal vascular resistance increased by 38 +/- 15% and 23 +/- 8% (p = 0.04) at - 30 mmHg LBNP, respectively. There was no change in cortical or medullary R2* (20.3 +/- 1.2 s(-1) vs 19.8 +/- 0.43 s(-1); 28.6 +/- 1.1 s(-1) vs 28.0 +/- 1.3 s(-1)). Conclusion The results suggest that an increase in sympathetic vasoconstrictor drive decreases kidney perfusion without a parallel reduction in oxygenation in healthy humans. This in turn indicates that sympathetic activation suppresses renal oxygen demand and supply equally, thus allowing adequate tissue oxygenation to be maintained.Cardiovascular Aspects of Radiolog

Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases

A large number of cardiovascular events are not prevented by current therapeutic regimens. In search for additional, innovative strategies, immune cells have been recognized as key players contributing to atherosclerotic plaque progression and destabilization. Particularly the role of innate immune cells is of major interest, following the recent paradigm shift that innate immunity, long considered to be incapable of learning, does exhibit immunological memory mediated via epigenetic reprogramming. Compelling evidence shows that atherosclerotic risk factors promote immune cell migration by pre-activation of circulating innate immune cells. Innate immune cell activation via metabolic and epigenetic reprogramming perpetuates a systemic low-grade inflammatory state in cardiovascular disease (CVD) that is also common in other chronic inflammatory disorders. This opens a new therapeutic area in which metabolic or epigenetic modulation of innate immune cells may result in decreased systemic chronic inflammation, alleviating CVD, and its co-morbidities

Liposomal prednisolone promotes macrophage lipotoxicity in experimental atherosclerosis

Atherosclerosis is a lipid-driven inflammatory disease, for which nanomedicinal interventions are under evaluation. Previously, we showed that liposomal nanoparticles loaded with prednisolone (LN-PLP) accumulated in plaque macrophages, however, induced proatherogenic effects in patients. Here, we confirmed in low-density lipoprotein receptor knockout (LDLr−/−) mice that LN-PLP accumulates in plaque macrophages. Next, we found that LN-PLP infusions at 10 mg/kg for 2 weeks enhanced monocyte recruitment to plaques. In follow up, after 6 weeks of LN-PLP exposure we observed (i) increased macrophage content, (ii) more advanced plaque stages, and (iii) larger necrotic core sizes. Finally, in vitro studies showed that macrophages become lipotoxic after LN-PLP exposure, exemplified by enhanced lipid loading, ER stress and apoptosis. These findings indicate that liposomal prednisolone may paradoxically accelerate atherosclerosis by promoting macrophage lipotoxicity. Hence, future (nanomedicinal) drug development studies are challenged by the multifactorial nature of atherosclerotic inflammation

The challenge of choosing in cardiovascular risk management

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.Cardiolog