Objective It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue. Setting, participants and outcome measures We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population. Results We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found. Conclusions High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Introduction For half a century, a high level of total cholesterol (TC) or low-density-lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated, and that statin treatment, in particular when used as primary prevention, is of doubtful benefit. Areas covered The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This paper delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis. Expert commentary Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality, and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.

Accurate characterisation of the mechanical properties of human atherosclerotic plaque is important for our understanding of the role of vascular mechanics in the development and treatment of atherosclerosis. The majority of previous studies investigating the mechanical properties of human plaque are based on tests of plaque tissue removed following autopsy. This study aims to characterise the mechanical behaviour of fresh human carotid plaques removed during endarterectomy and tested within 2h. A total of 50 radial compressive and 17 circumferential tensile uniaxial tests were performed on samples taken from 14 carotid plaques. The clinical classification of each plaque, as determined by duplex ultrasound is also reported. Plaques were classified as calcified, mixed or echolucent. Experimental data indicated that plaques were highly inhomogeneous; with variations seen in the mechanical properties of plaque obtained from individual donors and between donors. The mean behaviour of samples for each classification indicated that calcified plaques had the stiffest response, while echolucent plaques were the least stiff. Results also indicated that there may be a difference in behaviour of samples taken from different anatomical locations (common, internal and external carotid), however the large variability indicates that more testing is needed to reach significant conclusions. This work represents a step towards a better understanding of the in vivo mechanical behaviour of human atherosclerotic plaque.

To investigate experimentally the arterial wall/device compliance mismatch of four stent-graft devices and a multilayer flow modulator within the supra- and infrarenal locations for the treatment of abdominal aortic aneurysms (AAA). Five devices (MFM, EndurantII, Excluder, Zenith, and Fortron) were tested under physiological flow conditions within a flow simulator system comprising of a patient-specific thin-walled flexible AAA perfusion model with replicated intraluminal thrombus, supported by the spinal column. Devices were submitted to circumferential force tests and implanted in the perfusion model for circumferential arterial pressure/diameter measurements. Parameters, including radial resistive force, supra-/infrarenal compliance, pulsatile arterial energy loss (PAEL), pulse wave velocity (PWV), and wave reflection coefficient (Γ), were computed to characterise the devices' performance. The Zenith and EndurantII devices had the highest radial resistive force (up to 3 N/cm), while the Fortron device had the lowest (0.11 N/cm). Supra- and infrarenal compliance varied between 6.9-5.1 × 10(-4)/mmHg and 4.8-5.4 × 10(-4)/mmHg, respectively. Two devices (EndurantII and Excluder) significantly decreased infrarenal compliance by 13-26% (p < .001). Four devices increased the PAEL by 13-44% (p < .006). The PWV ranged from 10.9 m/s (MFM; p = .164) to 15.1 m/s (EndurantII; p < .001). There was an increase of 8-238% (p < .001) in the reflection coefficient for all devices. Commercially available endovascular devices lower the aortic wall compliance after implantation. The MFM was found to be the most compliant in the suprarenal region, while the Fortron device was the most compliant in the infrarenal region. Choosing the most compliant devices for treating AAAs produces positive gains in the aortic elastic recoil, thus minimising the device related complications.