ObjectiveIt is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.Setting, participants and outcome measuresWe sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.ResultsWe identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.ConclusionsHigh LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit. Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This article delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis. Expert commentary: Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.

Statins have been prescribed for primary prevention of cardiovascular disease (CVD) for nearly 3 decades. Throughout this period key opinion leaders in the field have been dismayed by the high rate of non-adherence of patients to follow their statin regimen. Hope et al., [1] have addressed this issue by providing a systematic review of research on predictors of statin adherence for primary prevention of CVD. However, their review does not address the ongoing debate as to whether statin treatment is warranted for primary prevention of CVD, nor does it adequately address concerns regarding adverse effects of statins. We have therefore written a commentary which provides a broader perspective on the benefits versus harms of statin therapy. Our perspective of the literature is that non-adherence to statin treatment for primary prevention of CVD is justified because the meager benefits are more than offset by the extensive harms.

Multiple sclerosis (MS) is a devastating disease that can occur in early life, progressing to rapid disability and loss of physical, psychosocial and economic functioning, significantly affecting quality of life. The traditional treatment for MS has been symptomatic, treating acute relapses without affecting the underlying disease. The introduction of interferon-beta (IFN beta) has offered significant clinical benefits by reducing the frequency of relapses and slowing disease progression. Although the costs of this treatment are high, the costs to society of caring for a patient disabled by MS are greater, and if IFN beta can delay disease progression in the longer term, the economic impact would be substantial. Previous pharmacoeconomic studies of IFN beta have suggested that benefits can only be achieved at extremely high cost, with reported cost-effectiveness measures of up to 1 million pounds sterling (Pound) per quality-adjusted life year (QALY) [1995 values]. However, these studies have considered only the short term benefits of IFN beta treatment: over 2 to 3 years, the impact of treatment on patients' quality of life is relatively small, and cost-utility analyses that do not consider longer term benefits nor include societal costs may be misleading. The model reported here is based on the hypothesis that the delay in disease progression seen in short term clinical trials is likely to continue if treatment is continued. The model also assumes that the delay in disease progression, which represents a reduction in brain atrophy, will result in lasting clinical benefits even if treatment is stopped. These assumptions are strongly supported by clinical trial data and the treatment hypothesis itself. A delay in disease progression will result in a significant improvement in functioning and quality of life, and if the costs associated with increased disability can be postponed, even long term treatment of MS with IFN beta can be shown to be cost effective. Using resource utilisation costs derived from an economic evaluation of MS in the UK, it was possible to calculate the impact of delaying disease progression in terms of both health service and societal costs. An estimate of mean disease progression in patients with MS treated with IFN beta-1a compared with patients who did not receive disease-modifying agents suggested that significant cost savings would be realised after about 12 years' treatment with IFN beta-1a. The application of utility scores to the disease progression curves also facilitated estimates of cost effectiveness, with cost per QALY values ranging from 27,036 Pounds after 2 years' treatment with IFN beta-1a to 37,845 Pounds after 20 years' treatment (1995 values).

We have evaluated dietary recommendations for people diagnosed with familial hypercholesterolaemia (FH), a genetic condition in which increased low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk for coronary heart disease (CHD). Recommendations for FH individuals have emphasised a low saturated fat, low cholesterol diet to reduce their LDL-C levels. The basis of this recommendation is the ‘diet-heart hypothesis’, which postulates that consumption of food rich in saturated fat increases serum cholesterol levels, which increases risk of CHD. We have challenged the rationale for FH dietary recommendations based on the absence of support for the diet-heart hypothesis, and the lack of evidence that a low saturated fat, low cholesterol diet reduces coronary events in FH individuals. As an alternative approach, we have summarised research which has shown that the subset of FH individuals that develop CHD exhibit risk factors associated with an insulin-resistant phenotype (elevated triglycerides, blood glucose, haemoglobin A1c (HbA1c), obesity, hyperinsulinaemia, high‐sensitivity C reactive protein, hypertension) or increased susceptibility to develop coagulopathy. The insulin-resistant phenotype, also referred to as the metabolic syndrome, manifests as carbohydrate intolerance, which is most effectively managed by a low carbohydrate diet (LCD). Therefore, we propose that FH individuals with signs of insulin resistance should be made aware of the benefits of an LCD. Our assessment of the literature provides the rationale for clinical trials to be conducted to determine if an LCD would prove to be effective in reducing the incidence of coronary events in FH individuals which exhibit an insulin-resistant phenotype or hypercoagulation risk.

No abstract

No abstract

No abstract