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Aims Low levels of HDL cholesterol have been associated with increased risk of infectious disease morbidity and mortality. Nuclear magnetic resonance (NMR) spectroscopy permits the measurement of HDL particle count and allows further subclassification according to particle size. We tested the hypothesis that low number of different HDL subfractions is associated with increased infectious disease morbidity and mortality. Methods and results HDL particle counts were measured using NMR spectroscopy in 30 195 individuals aged 22–99 years from the Copenhagen General Population Study. Using multiple-event Cox regression and cause-specific hazard models, we assessed risk of hospitalizations due to infection and infectious disease-related death, from 2003 through 2018. During follow-up, 9303 individuals had one or more infectious disease events, and 1558 experienced infectious disease-related death. In multifactorial adjusted analyses, low number of small and medium HDL particles was associated with increased risk of any infection and infectious disease-related death, whereas low number of large and extra-large HDL particles was not. A very high number of small and medium HDL particles was also associated with increased risk of any infection, but not with infectious disease-related death. For small and medium HDL particles and compared to individuals in the 91–95th percentile, hazard ratios (HRs) in individuals in the lowest percentile were 2.31 (95% confidence interval: 1.75, 3.05) for any infection and 3.23 (2.08, 5.02) for infectious disease-related death. For the highest percentile, corresponding HRs were 1.36 (1.07, 1.74) and 1.06 (0.57, 1.98), respectively. Individuals in the lowest percentile had increased risk of pneumonia (HR: 1.86; 95% confidence interval: 1.30, 2.65), sepsis (2.17; 1.37, 3.35), urinary tract infection (1.76; 1.17, 2.63), skin infection (1.87; 1.24, 2.81), gastroenteritis (1.78; 1.01, 3.16), and other infections (2.57; 1.28, 5.16). Conclusion Low number of the small HDL particles was associated with increased infectious disease morbidity and mortality. [ABSTRACT FROM AUTHOR]

This commentary refers to 'Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and non-cardiovascular mortality', by B.N. Wadström I et al i . https://doi.org/10.1093/eurheartj/ehac822 and the discussion piece 'Remnant cholesterol as a lipid-lowering target may have a long way to go', by Y.-X. In the PROMINENT trial, the remnant cholesterol-lowering effect was counteracted by an LDL cholesterol I increase i of similar magnitude in mg/dL, leading to an increase in apolipoprotein B as a marker of all atherogenic lipoproteins combined. In summary, to determine if remnant cholesterol-lowering therapy can lower residual ASCVD risk, randomized trials should include individuals with elevated remnant cholesterol levels and use a therapy that does not increase LDL cholesterol or apolipoprotein B as seen in the PROMINENT trial.[5] Since LDL cholesterol is the primary lipid target, remnant cholesterol-lowering therapy should be tested as add-on therapy in individuals receiving intensive LDL cholesterol-lowering treatment. [Extracted from the article]

Meta-analyses and Mendelian randomization (MR) may clarify the associations of smoking, blood cells and myeloproliferative neoplasms (MPN). We investigated the association of smoking with blood cells in the Danish General Suburban Population Study (GESUS, n = 11 083), by meta-analyses (including GESUS) of 92 studies (n = 531 741) and MR of smoking variant CHRNA3 (rs1051730[A]) in UK Biobank, and with MPN in a meta-analysis of six studies (n (total/cases):1 425 529/2187), totalling 2 307 745 participants. In the meta-analysis the random-effects standardized mean difference (SMD) in current smokers versus non-smokers was 0·82 (0·75-0·89, P = 2·0 * 10 -108 ) for leukocytes, 0·09 (-0·02 to 0·21, P = 0·12) for erythrocytes, 0·53 (0·42-0·64, P = 8·0 * 10 -22 ) for haematocrit, 0·42 (0·34-0·51, P = 7·1 * 10 -21 ) for haemoglobin, 0·19 (0·08-0·31, P = 1·2 * 10 -3 ) for mean corpuscular haemoglobin (MCH), 0·29 (0·19-0·39, P = 1·6 * 10 -8 ) for mean corpuscular volume (MCV), and 0·04 (-0·04 to 0·13, P = 0·34) for platelets with trends for ever/ex-/current smokers, light/heavy smokers and female/male smokers. Analyses presented high heterogeneity but low publication bias. Per allele in CHRNA3, cigarettes per day in current smokers was associated with increased blood cell counts (leukocytes, neutrophils), MCH, red cell distribution width (RDW) and MCV. The pooled fixed-effects odds ratio for MPN was 1·44 [95% confidence interval (CI): 1·33-1·56; P = 1·8 * 10 -19 ; I 2  = 0%] in current smokers, 1·29 (1·15-1·44; P = 8·0 * 10 -6 ; I 2  = 0%) in ex-smokers, 1·49 (1·26-1·77; P = 4·4 * 10 -6 ; I 2  = 0%) in light smokers and 2·04 (1·74-2·39, P = 2·3 * 10 -18 ; I 2  = 51%) in heavy smokers compared with non-smokers. Smoking is observationally and genetically associated with increased leukocyte counts and red blood cell indices (MCH, MCV, RDW) and observationally with risk of MPN in current and ex-smokers versus non/never-smokers., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)