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The article focuses on a study on the number needed to treat (NNT) with rosuvastatin to prevent first cardiovascular events and death among individuals with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity c-reactive protein. Data from Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) were use to determine absolute risk reductions and consequent NNT values. Those who participated in the trial had a median age of 66 years.

Background: Familial hypercholesterolemia (FH) is a condition with very high concentrations of low-density lipoprotein (LDL) cholesterol and high risk of ischemic heart disease including myocardial infarction. However, there is limited and contradictory information on whether FH and high LDL cholesterol per se confer high risk of ischemic stroke. We tested the hypotheses that individuals in the general population with FH and/or high LDL cholesterol have higher risk of ischemic stroke.Methods: The associations of FH and high LDL cholesterol with ischemic stroke risk were tested in both causal, genetic, and observational analyses using 106 412 individuals from the CGPS (Copenhagen General Population Study; 2823 ischemic strokes and 3792 myocardial infarctions) and/or 10 372 individuals from the CCHS (Copenhagen City Heart Study; 945 ischemic strokes and 1142 myocardial infarctions). FH causative mutations were LDLR W23X(rs267607213), W66G(rs121908025) and W556S, and APOB R3500Q(rs5742904). A Mendelian randomization design tested whether high LDL cholesterol per se has a causal effect on ischemic stroke risk, using a combination of the FH causative mutations and common genetic variants associated with high LDL cholesterol.Results: The cumulative incidences in individuals in the CGPS with and without FH causative mutations were similar for ischemic stroke ( P=0.50) but not for myocardial infarction ( P<0.001): at age 80 years, 4% and 7% of these individuals developed ischemic stroke and 20% and 8% myocardial infarction, with similar results in the CCHS. There was no association between clinical FH and ischemic stroke, except if personal premature ischemic heart disease was included in the clinical FH criteria. Ischemic heart disease at baseline was associated with higher ischemic stroke risk, explaining the higher ischemic stroke risk in those with high LDL cholesterol. For a 1 mmol/L higher LDL cholesterol, the genetic causal risk ratio was 1.11 (0.62-2.02) for ischemic stroke and 1.45 (1.08-1.93) for myocardial infarction.Conclusions: FH and high LDL cholesterol did not confer an increased risk of ischemic stroke. A positive association with ischemic stroke observed for some clinical FH criteria and high LDL cholesterol appears to be due to previous ischemic heart disease, rather than to high LDL cholesterol per se. [ABSTRACT FROM AUTHOR]

Background--Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown. Methods and Results--We studied 60 608 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease study, of whom 10 668 had IHD diagnosed between 1977 and 2011. We genotyped for variants affecting levels of nonfasting remnant cholesterol, LDL cholesterol, C-reactive protein by CRP alleles, and C-reactive protein by IL6R alleles. Using a multidirectional mendelian randomization design, we investigated possible causal associations between the lipoproteins and C-reactive protein and between the lipoproteins and IHD. A 1-mmol/L(39 mg/dL) higher level of nonfasting remnant cholesterol was associated observationally with a 37% (95% confidence interval, 35-39) higher C-reactive protein level and causally with a 28% (95% confidence interval, 10-48) higher level. For LDL cholesterol, a 1-mmol/L (39-mg/dL) higher level was associated observationally with a 7% (95% confidence interval, 6-7) higher C-reactive protein level, but we found no causal association. Likewise, higher levels of C-reactive protein did not associate causally with elevated nonfasting remnant cholesterol or LDL cholesterol. Finally, the causal risk ratio for IHD for a 1-mmol/L (39-mg/dL) higher level was 3.3 (95% confidence interval, 2.1-5.2) for nonfasting remnant cholesterol and 1.8 (95% confidence interval, 1.5-2.2) for LDL cholesterol. The causal associations for remnant cholesterol were present even in those without diabetes mellitus and obesity. Conclusions--Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation. [ABSTRACT FROM AUTHOR]

A response by Anette Varbo, Marianne Benn and colleagues to letters to the editor about their paper "Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation" published in "Circulation" is presented.