Serum cholesterol level is dependent on a number of agents involved in Cholesterol Serum Influx/Efflux
- Total Cholesterol
- HDL Cholesterol
- LDL Cholesterol
ANALYTICAL TRICKS AND TIPS
THE BIOLOGICAL CONTEXT
Google:cholesterol circadian rhythm
Hunt Study Shows Thyroid Prevents Heart Attacks
Endocrine and liver interaction: the role of endocrine pathways in NASH, 2009
- We also showed that human LXR-alpha gene expression and promoter activities were up-regulated by thyroid hormone.
Liver X receptor-alpha gene expression is positively regulated by thyroid hormone. 2007
Cholesterol as Risk Factor (before statins)
As you can see, those with serum cholesterol levels below 5mmol/L made up 10% of the population yet represented less than 3% of total coronary heart disease deaths. Those with serum cholesterol levels above 8mmol/L made up slightly more than 10% of the total population but accounted for over a quarter of coronary heart disease deaths.
In addition, mean serum cholesterol levels increase in the average population by age, in particular in women
Is this figure true?
Specificity, sensitivity etc.
PROs and CONTROs
out of a sample of around 2000 patients
J Am Geriatr Soc. 2003 Jan;51(1):80-4.
Does inflammation or undernutrition explain the low cholesterol-mortality association in high-functioning older persons? MacArthur studies of successful aging.
Hu P, Seeman TE, Harris TB, Reuben DB.
Multicampus Program in Geriatric Medicine and Gerontology, UCLA School of Medicine, Los Angeles, California 90095, USA. firstname.lastname@example.org
* J Am Geriatr Soc. 2004 Mar;52(3):469-70; author reply 471.
OBJECTIVES: To explore the effect of inflammation and undernutrition on the association between hypocholesterolemia and higher overall mortality in high-functioning older persons. DESIGN: Prospective cohort study. SETTING: Three U.S. communities. PARTICIPANTS: A cohort of 870 participants from the MacArthur Studies of Successful Aging. MEASUREMENTS: Baseline information was obtained for serum levels of cholesterol, C-reactive protein, interleukin-6, and albumin; body mass index; prevalent medical conditions; health behaviors; and medications. Crude and multivariate logistic regression analyses were used to examine the association between serum total cholesterol levels and 7-year all-cause mortality, while adjusting for potential confounders. RESULTS: In univariate analysis, the risk ratio of low serum total cholesterol level (<169 mg/dL) for 7-year total mortality was 1.90 (95% confidence interval (CI) = 1.18-3.07). The multiple adjusted risk ratios were 1.82 (95% CI = 1.10-3.00) after controlling for markers of inflammation and nutrition and 1.39 (95% CI = 0.80-2.40) after adjustment for additional cardiovascular risk factors. Sex was an important confounding variable that contributed to the observed inverse association between low serum cholesterol and overall mortality in univariate analysis. CONCLUSIONS: Hypocholesterolemia is not an independent risk factor for increased overall mortality in high-functioning community-dwelling older men and women. The association between low total cholesterol and high mortality observed in crude analysis is mainly confounded by common cardiovascular risk factors, rather than underlying inflammation or undernutrition.
Premeditated aggression is associated with serum cholesterol in abstinent drug and alcohol dependent men 2008
an inverse association between lower cholesterol and higher impulsivity and anxiety.
Serum leptin and cholesterol values in suicide attempters. 2002
Atmaca M, Kuloglu M, Tezcan E, Ustundag B, Gecici O, Firidin B.
Department of Psychiatry, Medical Faculty, Firat University, Elazig, Turkey. email@example.com
The growing number of studies examining the relationship between suicide and lipid metabolism are based upon studies suggesting that cholesterol-lowering procedures may increase the risk of death due to suicide or impulsive-aggressive behavior. Leptin seems to be strongly associated with lipid metabolism. In the present study, serum total cholesterol and leptin levels were compared in 24 suicide attempters and 24 healthy controls. The patients with suicide attempts had significantly lower serum cholesterol and leptin levels than controls. There was a positive correlation between cholesterol and leptin levels in both groups. Our results suggest that suicide attempts seem to be associated with decreased serum cholesterol and leptin levels. Copyright 2002 S. Karger AG, Basel
Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review , 2016
un altro fallimento l'evacetrapib;
Gli inibitori della CETP¹ (proteina di trasferimento degli esteri del colesterolo), nonostante la diminuzione del colesterolo LDL e l’aumento del colesterolo HDL, non sono riusciti ad ottenere risultati clinici.
Nello studio ACCELERATE è stato testato un altro inibitore della CEPT, l’evacetrapib, confrontandolo con placebo in pazienti ad alto rischio cardio-vascolare in trattamento standard. Lo studio, sponsorizzato dall’industria farmaceutica, ha riguardato 12.092 soggetti, un terzo dei quali era andato incontro ad un evento coronarico acuto nei 6 mesi precedenti.
Quasi tutti erano in terapia con statine. Lo studio, internazionale, è stato interrotto per futilità dopo un follow-up medio di 28 mesi. I livelli delle LDL erano notevolmente differenti tra i gruppi: con l’evacetrapib risultavano diminuite del 31% a fronte di un aumento del 6% con il placebo.
A livello delle HDL si è avuto un aumento del 133% con l’evacetrapib, contro il 2% con il placebo. Da questi esiti biochimici ci si sarebbero attesi risultati clinici degni di nota, invece gli endpoint considerati (decessi da cause cardio-vascolari, infarti, rivascolarizzazioni coronariche, stroke, angine instabili) si sono verificati del 12.9% dei soggetti trattati con il farmaco e nel 12.8% dei soggetti trattati con il placebo.
¹ La funzione della CETP consiste nella redistribuzione del colesterolo esterificato e dei trigliceridi tra le lipoproteine circolanti. Il punto centrale è il trasferimento di colesterolo dalle HDL alle LDL in cambio di trigliceridi. La sua inibizione pertanto provoca una diminuzione delle LDL ed un aumento delle HDL.
Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia, 2005
NPC1L1 , a recently identified relative of Niemann-Pick C1, was characterized to determine its subcellular location and potential function(s). NPC1L1 was highly expressed in HepG2 cells and localized in a subcellular vesicular compartment rich in the small GTPase Rab5. mRNA expression profiling revealed significant differences between mouse and man with highest expression found in human liver and significant expression in the small intestine. In contrast, liver expression in mouse was extremely low with mouse small intestine exhibiting the highest NPC1L1 expression. A mouse knock-out model of NPC1L1 was generated and revealed that mice lacking a functional NPC1L1 have multiple lipid transport defects. Surprisingly, lack of NPC1L1 exerts a protective effect against diet-induced hyperlipidemia. Further characterization of cell lines generated from wild-type and knock-out mice revealed that in contrast to wild-type cells, NPC1L1 cells exhibit aberrant plasma membrane uptake and subsequent transport of various lipids, including cholesterol and sphingolipids. Furthermore, lack of NPC1L1 activity causes a deregulation of caveolin transport and localization, suggesting that the observed lipid transport defects may be the indirect result of an inability of NPC1L1 null cells to properly target and/or regulate caveolin expression.