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.

In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, we present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and 'heme A', and thereby ATP generation. Statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency. Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. We propose that current statin treatment guidelines be critically reevaluated.

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Both transport delay (DELAY) and dynamic response (RESPONSE) of a mass spectrometer would theoretically result in considerable errors in the breath-by-breath calculation of VCO2 and VO2. However, curiously, the contribution of RESPONSE has been ignored. The purpose of this study is to quantify the error caused by RESPONSE. We found that RESPONSE of a mass spectrometer was regarded as a first-order response. We determined DELAY and time constant (T) of RESPONSE and compensated the on-line calculation for both DELAY and RESPONSE and for DELAY only. With T of 150 and 100 ms, deviations of VCO2 from the gas-collection method were 8 +/- 6 and 8 +/- 6 ml/min with compensation for both DELAY and RESPONSE, and 69 +/- 10 and 50 +/- 5 ml/min with compensation for DELAY only, respectively (mean +/- SD). Similar results were obtained with VO2. A computer simulation of error caused by RESPONSE disclosed that the error linearly increased with increasing T. We conclude that to be accurate within +/- 5% of the exact value, compensation should be made when T exceeds 25 ms.

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