Background: The role of high-density lipoprotein (HDL) function in cardiovascular disease represents an important emerging concept. The present study investigated whether HDL anti-inflammatory capacity is prospectively associated with first cardiovascular events in the general population. Methods: HDL anti-inflammatory capacity was determined as its ability to suppress TNFα (tumor necrosis factor α)–induced VCAM-1 (vascular cell adhesion molecule-1) mRNA expression in endothelial cells in vitro (results expressed as achieved percent reduction by individual HDL related to the maximum TNFα effect with no HDL present). In a nested case-control design of the PREVEND (Prevention of Renal and Vascular End Stage Disease) study, 369 cases experiencing a first cardiovascular event (combined end point of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization) during a median of 10.5 years of follow-up were identified and individually matched to 369 controls with respect to age, sex, smoking status, and HDL cholesterol. Baseline samples were available in 340 cases and 340 matched controls. Results: HDL anti-inflammatory capacity was not correlated with HDL cholesterol or hsCRP (high-sensitivity C-reactive protein). HDL anti-inflammatory capacity was significantly lower in cases compared with controls (31.6% [15.7–44.2] versus 27.0% [7.4–36.1]; P <0.001) and was inversely associated with incident CVD in a fully adjusted model (odds ratio [OR] per 1 SD, 0.74 [CI, 0.61–0.90]; P =0.002). Furthermore, this association was approximately similar with all individual components of the cardiovascular disease end point. The HDL anti-inflammatory was not correlated with cholesterol efflux capacity ( r =−0.02; P >0.05). When combining these 2 HDL function metrics in 1 model, both were significantly and independently associated with incident cardiovascular disease in a fully adjusted model (efflux: OR per 1 SD, 0.74; P =0.002; anti-inflammatory capacity: OR per 1 SD, 0.66; P <0.001). Adding HDL anti-inflammatory capacity improved risk prediction by the Framingham risk score, with a model likelihood-ratio statistic increase from 10.50 to 20.40 ( P =0.002). Conclusions: The HDL anti-inflammatory capacity, reflecting vascular protection against key steps in atherogenesis, was inversely associated with incident cardiovascular events in a general population cohort, independent of HDL cholesterol and HDL cholesterol efflux capacity. Adding HDL anti-inflammatory capacity to the Framingham risk score improves risk prediction.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Renal transplant recipients (RTRs) are known to have a high cardio-vascular disease (CVD) burden only partly explained by traditional CVD risk factors. The aim of this paper was therefore to determine: i) the prognostic value of autoantibodies against apoA-1 (anti-apoA-1 IgG) for incidence of CVD mortality, all-cause mortality and graft failure in RTR. Four hundred and sixty two (462) prospectively included RTRs were followed for 7.0 years. Baseline anti-apoA-1 IgG were determined and associations with incidence of CVD mortality (n = 48), all-cause mortality (n = 92) and graft failure (n = 39) were tested. Kaplan–Meier analyses demonstrated significant associations between tertiles of anti-apoA-1 IgG and CVD mortality (log rank test: p = 0.048). Adjusted Cox regression analysis showed a 54% increase in risk for CVD mortality for each anti-apoA-1 IgG levels standard deviation increase (hazard ratio [HR]: 1.54, 95% Confidence Interval [95%CI]: 1.14–2.05, p = 0.005), and a 33% increase for all-cause mortality (HR: 1.33; 95%CI: 1.06–1.67, p = 0.01), independent of CVD risk factors, renal function and HDL function. The association with all-cause mortality disappeared after excluding cases of CVD specific mortality. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-apoA-1 positivity for CVD mortality were 18.0%, 89.3%, 17.0%, and 90.0%, respectively. HDL functionality was not associated with anti-apoA-1 IgG levels. This prospective study demonstrates that in RTR, anti-apoA-1 IgG are independent predictors of CVD mortality and are not associated with HDL functionality.