Comment: The findings in this randomized controlled trial of 5,804 elderly participants are unequivocal: after a mean follow-up of 42 months, pravastatin demonstrated absolutely no difference in cognitive decline across any domain—including executive function, processing speed, or memory. It also celebrates a 24% RRR in cardiovascular mortality while the Absolute Risk Reduction (ARR) was a […]
Comment: This is another in a long line of studies where a randomized trial fails to show the benefit seen in observational cohorts. It is crucial to prioritize hard, randomized data because it is the only way to strip away the Healthy User Bias that plagues nutritional and pharmaceutical research. In observational studies, people who […]
Comment: Although meta-analyses are considered to be a higher level method, there are significant issues with them. I am always suspicious of pooled averages that ignore massive internal contradictions. This study reports high I2 for all-cause dementia ranging from 81.5% to 93%, which is a red flag. This number indicates that the studies being combined […]
Comment: This UK Biobank cohort study highlights a conflict between the narrative of statins as a vascular panacea and the documented reality that their use is associated with a 19% increased risk of incident Alzheimer’s disease (HR = 1.19). Looking carefully at the “protective” finding in APOE ε 4 homozygotes (HR = 0.72), there are […]
Comment: This was one of the earlier articles that really helped illustrate how important it is to keep the focus on absolute risk reduction to truly understand how effective an intervention is. Although this is a narrative review and has many risks of bias, other studies have borne out the concerns raised that the absolute […]
Comment: This study presents a fascinating potential validation of the ‘on-target’ theory regarding lipid lowering and metabolic risk. The fact that genetically mimicking PCSK9 inhibition yields the same small increase in diabetes risk as mimicking statins implies a common downstream pathway—likely intracellular cholesterol accumulation in pancreatic beta cells. This means we should be looking at […]
Comment: This study reinforces a critical physiological reality often obscured by the aggressive ‘lower is better’ paradigm for lipids. While the cardiovascular benefits of managing dyslipidemia are well-established, we frequently ignore the risks of hypocholesterolemia, such as in this study. Beyond the diabetes signal identified here, very low LDL (<70 mg/dL) has been consistently linked […]
Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins,
Comment: The traditional cardiological focus on lowering LDL-C in the elderly rests on a foundation of biochemical plausibility that is increasingly dismantled by actual survival data. This systematic review identified a critical physiological disconnect: for those over age 60, high LDL-C is not a mortality stressor but is actually associated with a longer lifespan. In […]
Comment: Another in a line of studies showing that our concept of cholesterol is wrong when it comes to the outcomes that matter. This one is particularly interesting as it breaks it down by age, showing that as we get older, higher cholesterol becomes more protective. The Wonk Debate – Audio Critique & Clinical Commentary: […]
