Encyclopedia of Gerontology and Population Aging

Living Edition
| Editors: Danan Gu, Matthew E. Dupre

Cholesterol Levels

  • Zhi-Jun Ou
  • Zhi-Wei Mo
  • Jing-Song OuEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-69892-2_1055-1



Cholesterol is indispensable for tissues and cells of human beings. It is not only an important substance participating in the formation of cell membranes but also a kind of material for the synthesis of bile acids, vitamin D, and steroid hormones. A human being can get cholesterol from routine diet. But the main source of cholesterol is synthesized by the liver. Cholesterol is transported through the blood by the apolipoprotein to vessels, adrenal gland, ovary, and other oranges or tissues. However, excessive cholesterol can be deposited in the vascular wall, leading to a variety of cardiovascular diseases. LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) are two main components of plasma cholesterol. High total cholesterol and high LDL-C levels are widely regarded as casual predicted factors for cardiovascular events. However, the relevance of HDL-C level to cardiovascular disease is not certain (Holmes et al. 2018). Cardiovascular disease is a leading cause of death worldwide, and it has now surpassed tumor diseases as the main killer of human beings. Monitoring and maintaining cholesterol homeostasis is an important means of preventing cardiovascular disease.


Aging is a natural process of human life. The functions of multiple organs and systems decline gradually, and the metabolism changes correspondingly, including cholesterol metabolism. The changes in plasma cholesterol levels cause various physiological and pathological effects, which in turn affect various organs of the body and interfere with normal physiological functions. As a result, it causes multiple diseases further, especially cardiovascular diseases. Very low-density lipoprotein cholesterol (VLDL-C) is formed from the liver cholesterol pool. Lipoprotein lipase (LPL) partially hydrolyzes VLDL-C to form medium-density lipoprotein cholesterol (IDL-C), a kind of low-density lipoprotein cholesterol (LDL-C) precursor. IDL-C is further hydrolyzed by liver lipase to form LDL-C. VLDL, IDL, and LDL transport triacylglycerol and cholesterol to tissues. High-density lipoprotein (HDL) can remove cholesterol from tissues and transport it back to the liver for metabolism. Elevated plasma level of LDL-C is a good predictive factor for cardiovascular disease risk (Ference et al. 2017), while the plasma level of high-density lipoprotein cholesterol (HDL-C) is negatively correlated with cardiovascular risk. There have been many simple and effective methods to reduce the level of LDL-C, and they can effectively decrease the risk of cardiovascular disease. However, elevating HDL-C level in the prevention and treatment of cardiovascular diseases is not necessarily effective as that we expected. Cardiovascular risk is not reduced by solely elevating plasma HDL-C level (Soria-Florido et al. 2020). It is necessary to improve the function of HDL while raising HDL-C level. Cholesterol level management is a simple and effective strategy to maintain the health of older people.

Key Research Findings

Changes in Cholesterol Metabolism During Aging

An abnormal feature of aging is the dysregulation of cholesterol metabolism of the whole body (Mc Auley and Mooney 2014; also see “Aging and Cholesterol Metabolism” in this volume). The clinical manifestation of this process is an age-related rise in the plasma levels of VLDL-C, IDL-C, and LDL-C (Abbott et al. 1983; Dayimu et al. 2019). VLDL-C, IDL-C, and LDL-C in the circulation can be absorbed into the hepatic cells by the LDL receptor (LDLr) (Veniant et al. 1998; Spolitu et al. 2019). However, the hepatic LDLr decreases with age, which results in the accumulation of LDL-C in the circulation (Millar et al. 1995; Mc Auley et al. 2012). On the contrary, the level of HDL-C decreases with age (Wilson et al. 1994; Cho et al. 2020). It has been reported that estrogen deficiency can cause female dyslipidemia (van Beresteijn et al. 1993; Taylor et al. 2017). In addition, the level of follicle-stimulating hormone (FSH) in peripheral blood circulation increases during menopause. Blocking the effect of FSH can inhibit hepatic cholesterol synthesis and reduces plasma cholesterol (Guo et al. 2019). Metabolism of cholesterol can be affected by the decline of organ function in the aging process of human body, and it is an important index to judge whether the aging process is normal.

Changes in Cholesterol Levels Affect Aging

Cardiovascular and cerebrovascular diseases are common diseases in older people. They are the leading cause of mortality internationally (Lozano et al. 2012). VLDL transports cholesterol in the circulation, where it is hydrolyzed to form IDL, a precursor of LDL. Then, IDL is further hydrolyzed to form LDL. Plasma VLDL-C is closely related to cardiovascular disease and it can be a predictor of coronary events (Sacks et al. 2000). Similarly, decreasing plasma IDL-C can effectively improve cardiovascular health (Zambon et al. 2014). Hirowatari introduced the anion-exchange chromatographic method to obtain IDL-C, which may serve as useful markers for risk of cardiovascular disease in chronic kidney disease patients with hemodialysis treatment (Hirowatari et al. 2012). Apolipoprotein (Apo)C-II, ApoC-III, and ApoE are three VLDL-associated apolipoproteins in de novo lipogenesis, glucose metabolism, complement activation, blood coagulation, and inflammation. In addition, ApoC-II/ApoC-III/ApoE correlated with a pattern of lipid species previously linked to coronary vascular disease (CVD) risk (Pechlaner et al. 2017). ApoC-III is a vital apolipoprotein for ApoB lipoproteins, which may contribute directly to atherogenesis by activating endothelial cells and recruiting monocytes to them (Kawakami et al. 2006a, b). Drug targeting ApoC-III succeeds in lowering plasma levels of ApoC-II, ApoC-III, triacylglycerols, and diacylglycerols, but increasing ApoA-I, ApoA-II, and ApoM without affecting ApoB-100 (Pechlaner et al. 2017). This supports the concept of targeting triacylglycerol-rich lipoproteins to reduce the risk of CVD.

Elevated plasma total cholesterol or LDL-C level is an important risk factor for cardiovascular events (Wadhera et al. 2016). LDL-C level is positively correlated with the risk of cardiovascular diseases. Atherosclerosis is the basic vasculopathy of multiple cardiovascular diseases, characterized by cholesterol deposition in macrophages in large and medium-sized arteries. Elevated plasma LDL-C level leads to increased adhesion of circulating monocytes to arterial endothelial cells. In addition, under various pathological stresses, LDL can undergo chemical modifications, turn to modified LDL or caused oxidized LDL. Modified LDL is cytotoxic, which makes LDL particles more proatherogenic, contributing to the damage of endothelial cells. Decreasing LDL-C level has been proved to be effective in reducing the incidence of cardiovascular diseases (Cannon et al. 2015).

High-density lipoprotein (HDL) can reversely transport cholesterol back to the liver for metabolism and excrete them from bile or stool to prevent lipid oxidation and deposition in the peripheral blood vessel wall (van Vlijmen and Herz 1999). In addition, HDL has been proved to be of anti-oxidative, anti-inflammatory, and protective for vascular endothelium (Nofer et al. 2002; Norata et al. 2005). The level of plasma HDL-C is negatively correlated with the risk of cardiovascular disease (Castelli et al. 1986). However, solely elevating plasma HDL-C level cannot effectively reduce the occurrence of cardiovascular events. Cholesteryl ester transfer protein (CETP) can promote the transport of cholesterol esters from HDL to LDL and VLDL (Ohashi et al. 2005). CETP inhibitors significantly increase the plasma HDL-C levels, but the risk of cardiovascular disease does not decrease accordingly (Schwartz et al. 2012). On the contrary, statins and exercise effectively reduce the cardiovascular risk while elevating plasma HDL-C level. But statin has limited effect on the increase of HDL-C level (Grundy et al. 2001). It is now believed that statins may play a protective role in improving the function of HDL. Similarly, exercise can not only increase the level of plasma HDL-C (Igarashi and Nogami 2019) but also improve the function of HDL (Blazek et al. 2013). Compared with HDL-C level, the function of HDL may be more critical. While suffering from pathological stress, HDL may lose its normal physiological function. At present, there is a lack of easy and effective methods to evaluate the function of HDL.

Examples of Application

Cholesterol level is of great importance for health. There are many clinical treatments for cholesterol dysregulation.

Application of Reducing LDL-C Level

A number of approaches for LDL-C lowering have been well studied, such as lifestyle interventions, pharmacologic treatment, and surgical therapy. When the baseline level of plasma LDL-C is high, lowering LDL-C can reduce cardiovascular mortality more effectively (Navarese et al. 2018).

Statin Therapy

Statin is an inhibitor of rate-limiting enzyme for cholesterol synthesis, hydroxy methylglutaryl coenzyme A reductase. It can reduce the production of endogenous cholesterol by inhibiting the synthesis of cholesterol, thus reducing LDL-C. A 1 mmol/L of LDL-C reduction was associated with 38% and 31% decreases in the relative risk of major vascular events (nonfatal myocardial infarction, coronary death, coronary revascularization, or stroke) in subgroups of 5-year predicted risk <5% and ≥5% to <10%, respectively (Mihaylova et al. 2012).

Nonstatin Pharmacologic Therapies

Many drugs have been used clinically to reduce LDL-C levels such as bile sequestrant resins, fibrates, nicotinic acid drugs, ezetimibe, and ω-3 fatty acid drugs. Cholestyramine, a bile acid sequestrant, 24 g/d lowers LDL-C levels by 53.4 mg/dL and TC levels by 50.7 mg/dL compared with matching placebo, with a trend toward reduced risk of CAD (odds ratio 0.81) (Ross et al. 2015). Fibrates can reduce triglycerides by 20–50%, LDL-C levels by up to 20% (Wierzbicki 2009). Fibrates alone can reduce cardiovascular events by 10–15% (Jun et al. 2010). The study of heart and renal protection (SHRP) trial shows that simvastatin, combined with ezetimibe, is able to significantly reduce the mortality of primary endpoint events such as nonfatal heart failure or coronary events and nonhemorrhagic stroke, and that the combined group did not show any adverse reactions like increased cancers, myolysis, or liver damage (Baigent et al. 2011).

Surgical Therapy

The partial ileal bypass has been shown to reduce LDL-C levels before statins appear. Liver transplantation has become the most effective method to implant LDLr in homozygous family hypercholesterolemia patients with gene mutations affecting the LDLr (Ishigaki et al. 2019). However, surgical therapy will inevitably cause great damage and many complications.

Application of Improving HDL Function

Several clinical studies have reported that elevating plasma HDL-C levels by CETP inhibitors fail to reduce cardiovascular risk. Currently, more attention has been paid to improve HDL function.

Apolipoprotein A-I (ApoA-I) Mimetic Peptide

ApoA-I, a major component protein of HDL, is an important carrier of ABCA1-mediated reverse cholesterol transport (Wang and Tall 2003). Rubin reported that the overexpression of ApoA-I increased the plasma levels of ApoA-I and HDL. As a result, the progress of arterial lipid plaque was impeded (Rubin et al. 1991). Studies have shown that ApoA-I mimetic peptide can improve HDL function, which not only inhibits the formation of atherosclerosis but also prevents the development of pulmonary hypertension (Sharma et al. 2014; Ou et al. 2005; Navab et al. 2002).


Otocka-Kmiecik and colleagues suggested that statins may play a role in improving HDL function and delaying the progression of atherosclerosis (Otocka-Kmiecik et al. 2012). Patients accepting simvastatin therapy, who were with noncoronary heart disease and scheduled to undergo heart operation, had a significant improvement in cardiac function, oxidative stress, and inflammatory reaction after cardiac surgery compared with the control group. Subgroup analysis showed that simvastatin significantly decreased HDL pro-inflammatory index in patients with valvular heart disease (Almansob et al. 2012). HDL of patients treated with simvastatin was improved significantly, suggesting that simvastatin promotes recovery of patients after cardiac surgery at least partially by improving HDL function (Chang et al. 2014).

Future Directions of Research

Many studies have achieved great success in reducing the level of LDL-C. New drugs for lowering LDL-C have been put on the market gradually, while HDL research is still in its infancy. More attention should be paid to the changes in HDL function and its subcomponents while suffering from diseases, and we should think about how to prevent new HDL from becoming pro-inflammatory HDL and improve the functions of pro-inflammatory HDL. There have been some methods to detect the function of HDL, such as its ability to reverse cholesterol transport, anti-apoptotic activity, the number of HDL particles in circulation, and so on. However, these methods have their own disadvantages, such as lack of standardization and unstable clinical correlation, which makes it impossible to integrate these indicators into risk prediction model or to evaluate the clinical efficacy of new lipid-lowering drugs. It is an urgent need to develop an easy and reliable method to accurately evaluate the function of HDL in clinical practice.


Cholesterol is an important nutrient. It not only participates in the composition and renewal of cell structure but also plays an important part in the signal transmission between human cells through the synthesis of steroid hormones. Cholesterol that ingested from food or synthesized by the liver is then transported to peripheral tissues by combining with apolipoproteins to form VLDL, IDL, and LDL. The excessive cholesterol from peripheral tissues is transported back to the liver to be discharged from the body through HDL, thus maintaining the delicate balance of cholesterol metabolism in the human body. If excessive cholesterol synthesis is ingested or peripheral cholesterol cannot be removed in time, excessive cholesterol will be deposited in peripheral tissues and organs, resulting in organ dysfunction and even disease. Aging is accompanied by the functional decline of organs, which affects the normal metabolism of cholesterol. Therefore, older people are prone to suffer from various lipid metabolic dysregulation, as well as cardiovascular and cerebrovascular diseases, which seriously threaten the health in older people. Various interventions have been applied to regulate the metabolism balance of cholesterol in clinical practice, and plasma cholesterol level has been used as a diagnosis reference of cardiovascular diseases. It is of great benefit to judge and utilize cholesterol levels in the prevention and treatment of various cardiovascular and cerebrovascular diseases in older people.



  1. Abbott RD, Garrison RJ, Wilson PW et al (1983) Joint distribution of lipoprotein cholesterol classes. The Framingham study. Arteriosclerosis 3(3):260–272.  https://doi.org/10.1161/01.ATV.3.3.260CrossRefGoogle Scholar
  2. Almansob MA, Xu B, Zhou L et al (2012) Simvastatin reduces myocardial injury undergoing noncoronary artery cardiac surgery: a randomized controlled trial. Arterioscler Thromb Vasc Biol 32(9):2304–2313.  https://doi.org/10.1161/atvbaha.112.252098CrossRefGoogle Scholar
  3. Baigent C, Landray MJ, Reith C et al (2011) The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (study of heart and renal protection): a randomised placebo-controlled trial. Lancet 377(9784):2181–2192.  https://doi.org/10.1016/s0140-6736(11)60739-3CrossRefGoogle Scholar
  4. Blazek A, Rutsky J, Osei K et al (2013) Exercise-mediated changes in high-density lipoprotein: impact on form and function. Am Heart J 166(3):392–400.  https://doi.org/10.1016/j.ahj.2013.05.021CrossRefGoogle Scholar
  5. Cannon CP, Blazing MA, Giugliano RP et al (2015) Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 372(25):2387–2397.  https://doi.org/10.1056/NEJMoa1410489CrossRefGoogle Scholar
  6. Castelli WP, Garrison RJ, Wilson PW et al (1986) Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham study. JAMA 256(20):2835–2838.  https://doi.org/10.1001/jama.1986.03380200073024CrossRefGoogle Scholar
  7. Chang FJ, Yuan HY, Hu XX et al (2014) High density lipoprotein from patients with valvular heart disease uncouples endothelial nitric oxide synthase. J Mol Cell Cardiol 74:209–219.  https://doi.org/10.1016/j.yjmcc.2014.05.015CrossRefGoogle Scholar
  8. Cho KH, Park HJ, Kim JR (2020) Decrease in serum HDL-C level is associated with elevation of blood pressure: correlation analysis from the Korean National Health and nutrition examination survey 2017. Int J Environ Res Public Health 17(3).  https://doi.org/10.3390/ijerph17031101
  9. Dayimu A, Wang C, Li J et al (2019) Trajectories of lipids profile and incident cardiovascular disease risk: a longitudinal cohort study. J Am Heart Assoc 8(21):e013479.  https://doi.org/10.1161/jaha.119.013479CrossRefGoogle Scholar
  10. Ference BA, Ginsberg HN, Graham I et al (2017) Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel. Eur Heart J 38(32):2459–2472.  https://doi.org/10.1093/eurheartj/ehx144CrossRefGoogle Scholar
  11. Grundy SM, D’Agostino RB Sr, Mosca L et al (2001) Cardiovascular risk assessment based on US cohort studies: findings from a National Heart, lung, and blood institute workshop. Circulation 104(4):491–496.  https://doi.org/10.1161/01.CIR.104.4.491CrossRefGoogle Scholar
  12. Guo Y, Zhao M, Bo T et al (2019) Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol. Cell Res 29:151–166.  https://doi.org/10.1038/s41422-018-0123-6CrossRefGoogle Scholar
  13. Hirowatari Y, Homma Y, Yoshizawa J et al (2012) Increase of electronegative-LDL-fraction ratio and IDL-cholesterol in chronic kidney disease patients with hemodialysis treatment. Lipids Health Dis 11:111.  https://doi.org/10.1186/1476-511x-11-111CrossRefGoogle Scholar
  14. Holmes MV, Millwood IY, Kartsonaki C et al (2018) Lipids, lipoproteins, and metabolites and risk of myocardial infarction and stroke. J Am Coll Cardiol 71(6):620–632.  https://doi.org/10.1016/j.jacc.2017.12.006CrossRefGoogle Scholar
  15. Igarashi Y, Nogami Y (2019) Response of lipids and lipoproteins to regular aquatic endurance exercise: a meta-analysis of randomized controlled trials. J Atheroscler Thromb 26(1):14–30.  https://doi.org/10.5551/jat.42937CrossRefGoogle Scholar
  16. Ishigaki Y, Kawagishi N, Hasegawa Y et al (2019) Liver transplantation for homozygous familial hypercholesterolemia. J Atheroscler Thromb 26:121–127.  https://doi.org/10.5551/jat.RV17029CrossRefGoogle Scholar
  17. Jun M, Foote C, Lv J et al (2010) Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375(9729):1875–1884.  https://doi.org/10.1016/s0140-6736(10)60656-3CrossRefGoogle Scholar
  18. Kawakami A, Aikawa M, Alcaide P et al (2006a) Apolipoprotein CIII induces expression of vascular cell adhesion molecule-1 in vascular endothelial cells and increases adhesion of monocytic cells. Circulation 114(7):681–687.  https://doi.org/10.1161/circulationaha.106.622514CrossRefGoogle Scholar
  19. Kawakami A, Aikawa M, Libby P et al (2006b) Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation 113(5):691–700.  https://doi.org/10.1161/circulationaha.105.591743CrossRefGoogle Scholar
  20. Lozano R, Naghavi M, Foreman K et al (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet 380(9859):2095–2128.  https://doi.org/10.1016/s0140-6736(12)61728-0CrossRefGoogle Scholar
  21. Mc Auley MT, Mooney KM (2014) Lipid metabolism and hormonal interactions: impact on cardiovascular disease and healthy aging. Expert Rev Endocrinol Metab 9(4):357–367.  https://doi.org/10.1586/17446651.2014.921569CrossRefGoogle Scholar
  22. Mc Auley MT, Wilkinson DJ, Jones JJ et al (2012) A whole-body mathematical model of cholesterol metabolism and its age-associated dysregulation. BMC Syst Biol 6:130.  https://doi.org/10.1186/1752-0509-6-130CrossRefGoogle Scholar
  23. Mihaylova B, Emberson J, Blackwell L et al (2012) The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380(9841):581–590.  https://doi.org/10.1016/s0140-6736(12)60367-5CrossRefGoogle Scholar
  24. Millar JS, Lichtenstein AH, Cuchel M et al (1995) Impact of age on the metabolism of VLDL, IDL, and LDL apolipoprotein B-100 in men. J Lipid Res 36(6):1155–1167Google Scholar
  25. Navab M, Anantharamaiah GM, Hama S et al (2002) Oral administration of an Apo A-I mimetic peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation 105(3):290–292.  https://doi.org/10.1161/hc0302.103711CrossRefGoogle Scholar
  26. Navarese EP, Robinson JG, Kowalewski M et al (2018) Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: a systematic review and meta-analysis. JAMA 319(15):1566–1579.  https://doi.org/10.1001/jama.2018.2525CrossRefGoogle Scholar
  27. Nofer JR, Kehrel B, Fobker M et al (2002) HDL and arteriosclerosis: beyond reverse cholesterol transport. Atherosclerosis 161(1):1–16.  https://doi.org/10.1016/S0021-9150(01)00651-7CrossRefGoogle Scholar
  28. Norata GD, Callegari E, Marchesi M et al (2005) High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells. Circulation 111(21):2805–2811.  https://doi.org/10.1161/circulationaha.104.472886CrossRefGoogle Scholar
  29. Ohashi R, Mu H, Wang X et al (2005) Reverse cholesterol transport and cholesterol efflux in atherosclerosis. QJM 98(12):845–856.  https://doi.org/10.1093/qjmed/hci136CrossRefGoogle Scholar
  30. Otocka-Kmiecik A, Mikhailidis DP, Nicholls SJ et al (2012) Dysfunctional HDL: a novel important diagnostic and therapeutic target in cardiovascular disease? Prog Lipid Res 51(4):314–324.  https://doi.org/10.1016/j.plipres.2012.03.003CrossRefGoogle Scholar
  31. Ou J, Wang J, Xu H et al (2005) Effects of D-4F on vasodilation and vessel wall thickness in hypercholesterolemic LDL receptor-null and LDL receptor/apolipoprotein A-I double-knockout mice on Western diet. Circ Res 97(11):1190–1197.  https://doi.org/10.1161/01.RES.0000190634.60042.cbCrossRefGoogle Scholar
  32. Pechlaner R, Tsimikas S, Yin X et al (2017) Very-low-density lipoprotein-associated Apolipoproteins predict cardiovascular events and are lowered by inhibition of APOC-III. J Am Coll Cardiol 69(7):789–800.  https://doi.org/10.1016/j.jacc.2016.11.065CrossRefGoogle Scholar
  33. Ross S, D’Mello M, Anand SS et al (2015) Effect of bile acid Sequestrants on the risk of cardiovascular events: a Mendelian randomization analysis. Circ Cardiovasc Genet 8(4):618–627.  https://doi.org/10.1161/circgenetics.114.000952CrossRefGoogle Scholar
  34. Rubin EM, Krauss RM, Spangler EA et al (1991) Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 353(6341):265–267.  https://doi.org/10.1038/353265a0CrossRefGoogle Scholar
  35. Sacks FM, Alaupovic P, Moye LA et al (2000) VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the cholesterol and recurrent events (CARE) trial. Circulation 102(16):1886–1892.  https://doi.org/10.1161/01.CIR.102.16.1886CrossRefGoogle Scholar
  36. Schwartz GG, Olsson AG, Abt M et al (2012) Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 367(22):2089–2099.  https://doi.org/10.1056/NEJMoa1206797CrossRefGoogle Scholar
  37. Sharma S, Umar S, Potus F et al (2014) Apolipoprotein A-I mimetic peptide 4F rescues pulmonary hypertension by inducing microRNA-193-3p. Circulation 130(9):776–785.  https://doi.org/10.1161/circulationaha.114.007405CrossRefGoogle Scholar
  38. Soria-Florido MT, Castaner O, Lassale C et al (2020) Dysfunctional high-density lipoproteins are associated with a greater incidence of acute coronary syndrome in a population at high cardiovascular risk: a nested case-control study. Circulation 141(6):444–453.  https://doi.org/10.1161/circulationaha.119.041658CrossRefGoogle Scholar
  39. Spolitu S, Okamoto H, Dai W et al (2019) Hepatic glucagon signaling regulates PCSK9 and low-density lipoprotein cholesterol. Circ Res 124(1):38–51.  https://doi.org/10.1161/circresaha.118.313648CrossRefGoogle Scholar
  40. Taylor HS, Giudice LC, Lessey BA et al (2017) Treatment of endometriosis-associated pain with Elagolix, an oral GnRH antagonist. N Engl J Med 377(1):28–40.  https://doi.org/10.1056/NEJMoa1700089CrossRefGoogle Scholar
  41. van Beresteijn EC, Korevaar JC, Huijbregts PC et al (1993) Perimenopausal increase in serum cholesterol: a 10-year longitudinal study. Am J Epidemiol 137(4):383–392.  https://doi.org/10.1093/oxfordjournals.aje.a116686CrossRefGoogle Scholar
  42. van Vlijmen BJ, Herz J (1999) Gene targets and approaches for raising HDL. Circulation 99(1):12–14.  https://doi.org/10.1161/01.CIR.99.1.12CrossRefGoogle Scholar
  43. Veniant MM, Zlot CH, Walzem RL et al (1998) Lipoprotein clearance mechanisms in LDL receptor-deficient “Apo-B48-only” and “Apo-B100-only” mice. J Clin Invest 102(8):1559–1568.  https://doi.org/10.1172/jci4164CrossRefGoogle Scholar
  44. Wadhera RK, Steen DL, Khan I et al (2016) A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. J Clin Lipidol 10(3):472–489.  https://doi.org/10.1016/j.jacl.2015.11.010CrossRefGoogle Scholar
  45. Wang N, Tall AR (2003) Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 23(7):1178–1184.  https://doi.org/10.1161/01.Atv.0000075912.83860.26CrossRefGoogle Scholar
  46. Wierzbicki AS (2009) Fibrates in the treatment of cardiovascular risk and atherogenic dyslipidaemia. Curr Opin Cardiol 24(4):372–379.  https://doi.org/10.1097/HCO.0b013e32832c0b3dCrossRefGoogle Scholar
  47. Wilson PW, Anderson KM, Harris T et al (1994) Determinants of change in total cholesterol and HDL-C with age: the Framingham study. J Gerontol 49(6):M252–M257.  https://doi.org/10.1093/geronj/49.6.M252CrossRefGoogle Scholar
  48. Zambon A, Zhao XQ, Brown BG et al (2014) Effects of niacin combination therapy with statin or bile acid resin on lipoproteins and cardiovascular disease. Am J Cardiol 113(9):1494–1498.  https://doi.org/10.1016/j.amjcard.2014.01.426CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Division of Hypertension and Vascular Diseases, Heart CenterThe First Affiliated Hospital, Sun Yat-sen UniversityGuangzhouPeople’s Republic of China
  2. 2.Division of Cardiac Surgery, Heart CenterThe First Affiliated Hospital, Sun Yat-sen UniversityGuangzhouPeople’s Republic of China

Section editors and affiliations

  • Xiao-Li Tian
    • 1
  1. 1.Human Aging Research Institute (HARI), School of Life ScienceNanchang UniversityNanchangChina