Cholesterol Reduction Yields Clinical Benefit

Gould, A. Lawrence; Rossouw, Jacques E.; Santanello, Nancy C.; Heyse, Joseph F.; Furberg, Curt D.

doi:10.1161/01.cir.91.8.2274

Cited by 272 publications

(152 citation statements)

References 54 publications

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“…A similar pattern of the protective effects of cholesterol has also been found among adults older than 55, who evince an inverse relationship between total cholesterol and several infectious diseases (Iribarren et al 1998). Conversely, studies of younger adults reveal that the effect of total cholesterol on noncardiovascular mortality is neutral (Kronmal et al 1993;Krumholz et al 1994;Gould et al 1995). Another study finds a trend of increased noncardiovascular mortality with decreased LDL, in both placebo and treatment groups (Razzolini et al 2008).…”

Section: Cholesterol and Infectionsupporting

confidence: 54%

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Amir¹,

Fessler²

2013

The Quarterly Review of Biology

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Section: Cholesterol and Infectionsupporting

confidence: 54%

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Amir¹,

Fessler²

2013

The Quarterly Review of Biology

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“…Gemfibrozil, unlike other fibrates, has also been shown to increase plasma apo E concentrations (24,66). Fibrates and other peroxisome proliferators clearly exhibit a wide array of biological activities and potential side-effects both in rodents and in humans (67). In particular, the impact of fibrates on HDL metabolism is obviously not restricted to apo A-I, since several clinical studies evidenced an increase in plasma apo A-II concentrations in fenofibrate-treated patients (6,27,43).…”

Section: Discussionmentioning

confidence: 99%

Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice.

Berthou¹,

Duverger²,

Emmanuel³

et al. 1996

J. Clin. Invest.

239

158

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The regulation of liver apolipoprotein (apo) A-I gene expression by fibrates was studied in human apo A-I transgenic mice containing a human genomic DNA fragment driving apo A-I expression in liver. Treatment with fenofibrate (0.5% wt/wt) for 7 d increased plasma human apo A-I levels up to 750% and HDL-cholesterol levels up to 200% with a shift to larger particles. The increase in human apo A-I plasma levels was time and dose dependent and was already evident after 3 d at the highest dose (0.5% wt/wt) of fenofibrate. In contrast, plasma mouse apo A-I concentration was decreased after fenofibrate in nontransgenic mice. The increase in plasma human apo A-I levels after fenofibrate treatment was associated with a 97% increase in hepatic human apo A-I mRNA, whereas mouse apo A-I mRNA levels decreased to 51%. In nontransgenic mice, a similar down-regulation of hepatic apo A-I mRNA levels was observed. Nuclear run-on experiments demonstrated that the increase in human apo A-I and the decrease in mouse apo A-I gene expression after fenofibrate occurred at the transcriptional level. Since part of the effects of fibrates are mediated through the nuclear receptor PPAR (peroxisome proliferator-activated receptor), the expression of the acyl CoA oxidase (ACO) gene was measured as a control of PPAR activation. Both in transgenic and nontransgenic mice, fenofibrate induced ACO mRNA levels up to sixfold. When transgenic mice were treated with gemfibrozil (0.5% wt/wt) plasma human apo A-I and HDL-cholesterol levels increased 32 and 73%, respectively, above control levels. The weaker effect of this compound on human apo A-I and HDL-cholesterol levels correlated with a less pronounced impact on ACO mRNA levels (a threefold increase) suggesting that the level of induction of human apo A-I gene is related to the PPAR activating potency of the fibrate used. Treatment of human primary hepatocytes with fenofibric acid (500 M) provoked an 83 and 50% increase in apo A-I secretion and mRNA levels, respectively, supporting that a direct action of fibrates on liver human apo A-I production leads to the observed increase in plasma apo A-I and HDLcholesterol. ( J. Clin. Invest. 1996. 97:2408-2416.)

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“…Raised serum cholesterol concentration is a well-established risk factor estimated to explain four-fifths of the geographic variation in CHD mortality . A meta-analysis (Gould et al, 1995) has estimated that a reduction of serum cholesterol by 10% would reduce cardiovascular death by 13% and total mortality by 10%.…”

Section: Introductionmentioning

confidence: 99%

Intake of dietary plant sterols is inversely related to serum cholesterol concentration in men and women in the EPIC Norfolk population: a cross-sectional study

et al. 2004

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Objective: We examined the relation between intake of natural dietary plant sterols and serum lipid concentrations in a freeliving population. Design, setting and participants: Cross-sectional population-based study of 22 256 men and women aged 39-79 y resident in Norfolk, UK, participating in the European Prospective Investigation into Cancer (EPIC-Norfolk). Main exposure and outcome measures: Plant sterol intake from foods and concentrations of blood lipids. Results: Mean concentrations of total cholesterol and low-density lipoprotein cholesterol, adjusted for age, body mass index and total energy intake, decreased with increasing plant sterol intake in men and women. Mean total serum cholesterol concentration for men in the highest fifth of plant sterol intake (mean intake 463 mg daily) was 0.25 mmol/l lower and for lowdensity lipoprotein cholesterol 0.14 mmol/l lower than those in the lowest fifth of plant sterol consumption (mean intake 178 mg daily); the corresponding figures in women were 0.15 and 0.13 mmol/l. After adjusting for saturated fat and fibre intakes, the results for total cholesterol and low-density lipoprotein cholesterol were similar, although the strength of the association was slightly reduced. Conclusions: In a free-living population, a high intake of plant sterols is inversely associated with lower concentrations of total and low-density lipoprotein serum cholesterol. The plant sterol content of foods may partly explain diet-related effects on serum cholesterol concentration.

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Cholesterol Reduction Yields Clinical Benefit

Abstract: The results suggest that cholesterol lowering itself is beneficial but that specific adverse effects of fibrates and hormones increase the risk of CHD (hormones only), non-CHD, and total mortality.

Cited by 272 publications

References 54 publications

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice.

Intake of dietary plant sterols is inversely related to serum cholesterol concentration in men and women in the EPIC Norfolk population: a cross-sectional study

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