Background— Aortic stenosis (AS) is an active process with similarities to atherosclerosis. The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS. Methods and Results— This was a randomized, double-blind, placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering. The patients were randomized to receive either placebo or rosuvastatin 40 mg daily. A total of 269 patients were randomized: 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo. Annual echocardiograms were performed to assess AS progression, which was the primary outcome; the median follow-up was 3.5 years. The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8±11.1 to 57.8±22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6±10.9 mm Hg at baseline to 54.8±19.8 mm Hg at the end of follow-up. The annualized increase in the peak AS gradient wa...

Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis Results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial

ContextLandmark clinical trials have demonstrated the survival benefits of
statins, with benefits usually starting after 1 to 2 years of treatment. Research
prior to these trials of older lipid-lowering agents demonstrated low levels
of 1-year adherence.ObjectiveTo compare 2-year adherence following statin initiation in 3 cohorts
of patients: those with recent acute coronary syndrome (ACS), those with chronic
coronary artery disease (CAD), and those without coronary disease (primary
prevention).Design and SettingCohort study using linked population-based administrative data from
Ontario.PatientsAll patients aged 66 years or older who received at least 1 statin prescription
between January 1994 and December 1998 and who did not have a statin prescription
in the prior year were followed up for 2 years from their first statin prescription.
There were 22 379 patients in the ACS, 36 106 in the chronic CAD,
and 85 020 in the primary prevention cohorts.Main Outcome MeasuresAdherence to statins, defined as a statin being dispensed at least every
120 days after the index prescription for 2 years.ResultsTwo-year adherence rates in the cohorts were only 40.1% for ACS, 36.1%
for chronic CAD, and 25.4% for primary prevention. Relative to the ACS cohort,
nonadherence was more likely among patients receiving statins in the chronic
CAD (relative risk [RR], 1.14; 95% CI, 1.11-1.16) and primary prevention cohorts
(RR, 1.92; 95% CI, 1.87-1.96).ConclusionsElderly patients with and without recent ACS have low rates of adherence
to statins. This suggests that many patients initiating statin therapy may
receive no or limited benefit from statins because of premature discontinuation.

Adherence with statin therapy in elderly patients with and without acute coronary syndromes

During the last several years interest has focused on the importance of the lipid-transporting apolipoproteins--apoB transports all potentially atherogenic very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and LDL particles, and apoA-I transports and acts as the major antiatherogenic protein in the HDL particles. The evidence for the apoB/apoA-I ratio being a strong, new risk factor for cardiovascular (CV) disease and a target for lipid-lowering therapy is reviewed. Results from clinical prospective studies and lipid-lowering trials in healthy subjects and in patients with different clinical manifestations of atherosclerosis are reported. Risk of nonfatal and fatal myocardial infarction and stroke, and manifestations of atherosclerosis documented by angiographic, ultrasound and other techniques has been related to conventional lipids and apolipoproteins (apo). The cholesterol balance determined as the apoB/apoA-I ratio has repeatedly been shown to be a better marker than lipids, lipoproteins and lipid ratios. The results indicate that the apoB/apoA-I ratio is a simple, accurate and new risk factor for CV disease--the lower the apoB/apoA-I ratio, the lower is the risk. Guidelines should be developed in order to recognize the important clinical risk information embedded in the apoB/apoA-I ratio.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2006.01643.x

The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy--a review of the evidence.

Objective To establish the predictive accuracy of the Framingham risk score for coronary heart disease in a representative British population. Design Prospective cohort study. Setting 24 towns in the United Kingdom. Participants 6643 British men aged 40-59 years and free from cardiovascular disease at entry into the British regional heart study. Main outcome measures Comparison of observed 10 year coronary heart disease mortality and event rates with predicted rates for each individual, using the relevant Framingham risk equation. Results Of 6643 men, 2.8% (95% confidence interval 2.4% to 3.2%) died from coronary heart disease compared with 4.1% predicted (relative overestimation 47%, P Conclusion Guidelines for the primary prevention of coronary heart disease advocate offering preventive measures to individuals at high risk. Currently recommended risk scoring methods derived from the Framingham study significantly overestimate the absolute coronary risk assigned to individuals in the United Kingdom.

https://www.bmj.com/content/bmj/327/7426/1267.full.pdf

Predictive accuracy of the Framingham coronary risk score in British men:prospective cohort study

Background Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)–low HDL-C dyslipidemia. Methods A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. Results The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles ( P Conclusion Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/752318/ioi01029.pdf

Total Cholesterol/HDL Cholesterol Ratio vs LDL Cholesterol/HDL Cholesterol Ratio as Indices of Ischemic Heart Disease Risk in Men: The Quebec Cardiovascular Study

1Although the age-adjusted rate of death from cardiovascular disease is declining, the prevalence of cardiac conditions is increasing because of the growing number of elderly people, better acute care and improved survival. 1 People with heart disease often remain in the community, requiring long-term medical care. In quantitative terms, $7.3 billion (17%) of total direct health care costs and $12.3 billion (14.5%) of total indirect health care costs for all disease categories can be attributed to cardiovascular disease. 1 The largest proportion of cardiovascular diseases is represented by CAD and cerebral and peripheral vascular disease. During the past 3 decades efficacious strategies have been developed for primary and secondary prevention of these diseases. These strategies involve general lifestyle changes (to promote healthy diet, optimal weight, physical activity, moderate or no alcohol consumption, and smoking cessation), treatment of high blood pressure, control of diabetes mellitus and, in particular, treatment of dyslipidemias. The causal relation between hypercholesterolemia and atherosclerosis was established more than 80 years ago by Anitschkow. 2 Since the 1950s, there have been steady improvements in our ability to treat hypercholesterolemia through diet and the use of lipid-lowering drugs. The earliest angiographic and clinical studies demonstrated that intensive therapy to lower low-density lipoprotein cholesterol (LDL-C) levels slowed the progression of atherosclerosis and decreased the incidence of major coronary events; 3,4 however, these early studies did not have sufficient power to detect beneficial mortality trends. The results of these early clinical studies and the extensive epidemiological data on the relation between plasma lipoprotein levels and CAD, as well as experimental information from animal models of atherosclerosis, led to the development of policies to manage and treat lipid disorders. In Canada, guidelines for the management of hypercholesterolemia were first issued in 1988. 5 Major clinical trials carried out over the past decade have shown a clear benefit of LDL-C reduction in terms of both CAD events and total mortality. A similar reduction in the relative risk of coronary events has been documented in patients with and without clinically evident CAD and in patients with mild or severe dyslipidemia.

/pdf/report-of-the-working-group-on-hypercholesterolemia-and-q54v22un4q.pdf

J. George Fodor

Papers

Report of the Working Group on Hypercholesterolemia and Other Dyslipidemias