Amarenco et al. 2008(1111. Amarenco P, Labreuche J, Touboul PJ. High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: A systematic review. Atherosclerosis. 2008;196(2):489-96.) |
10 prospective cohorts and 8 case-control studies analyzed the outcome of stroke. Six longitudinal studies and 36 cross-sectional studies were included to analyze carotid thickness. |
Only 2 prospective studies did not show an association between HDL-C and stroke. Five studies showed a reduction by 11-15% of the risk for stroke for 10 mg/dL increase in HDL-C. Of the case-control studies, only 3 did not show an association, with a mean adjusted RR of 0.66 for each 10 mg/dL increase in HDL. As to carotid atherosclerosis, data show a tendency towards protective effect |
Prospective Studies Collaboration 2007(1212. Prospective Studies Collaboration, Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet. 2007;370(9602):1829-39.) |
61 observational prospective studies, with age range of 40 to 89 years, included 222 thousand longevous elderly persons per year. Information on HDL was available for 150,000 individuals. Average follow-up was 13 years. |
Among the indices that assessed HDL-C, the TC/HDL ratio obtained the best positive predictive value for cardiovascular mortality. An increase of 0.33 mmol/L in HDL-C or a reduction of 1.33 in TC/HDL-C reduced by about 33% the mortality by CAD |
Vliet et al., 2010(1313. van Vliet P, Oleksik AM, van Heemst D, de Craen AJ, Westendorp RG Dynamics of traditional metabolic risk factors associate with specific causes of death in old age. J Gerontol A Biol Sci Med Sci. 2010;65(5):488-94.) |
599 participants of the Leiden 85-plus study, aged 85 years, 34% males. Follow-up of 5 years and for mortality,10 years |
Among the markers studied, HDL-C and CRP increased during follow-up in those aged 85 to 90 years (p < 0.001). The participants with the smallest increase in HDL-C presented the greatest mortality (p < 0.001). CRP was analyzed along with TC, HDL-C, LDL-C, hemoglobin, blood glucose, albumin, and leukocytes, showing a significant association with total mortality and mortality by cancer (p < 0.01) |
Willems, 2010(1414. Willems JM, Trompet S, Blauw GJ, Westendorp RG, de Craen AJ. White blood cell count and C-reactive protein are independent predictors of mortality in the oldest old. J Gerontol A Biol Sci Med Sci. 2010;65(7):764-8.) |
599 participants of the Leiden 85-plus study, aged 85 years, 34% males. Follow-up of 5 years and for mortality,10 years |
CRP showed a significant association with mortality, with a relative risk of 1.17 (1.09-1.33) |
Cesari et al., 2009(1515. Cesari M, Onder G, Zamboni V, Capoluongo E, Russo A, Bernabei R, et al. C-reactive protein and lipid parameters in older persons aged 80 years and older. J Nutr Health Aging. 2009;13(7):587-93.) |
336 participants of the ilSIRENTE study aged over 80 years, with a mean age of 85.8 years. Follow-up of 2 years |
CRP showed an inverse relation with HDL-C, but with statistical signifcance only in the group over 85 years of age. CRP was the only biomarker with a significant association with mortality after linear regression+D31 |
Kravitz et al., 2009(1616. Kravitz BA, Corrada MM, Kawas CH. High levels of serum C-reactive protein are associated with greater risk of all-cause mortality, but not dementia, in the oldest-old: results from The 90+ Study. J Am Geriatr Soc. 2009;57(4):641-6.) |
227 participants of the Vitality 90+ study, age range of 90-102 years, and mean age of 93.9 years, 62.1% of them females |
Elderly subjects with CRP ≥ 0.5mg/dL had a significant increase in mortality risk, with a HR: 1.7 (CI: 1-2.9), whereas in individuals with the APOE4 allele the association+D15 was even stronger, with RR: 5.6 (CI:1-30.7) |
Ruijter et al., 2008(1717. de Ruijter W, Westendorp RG, Assendelft WJ, den Elzen W P, de Craen AJ, le Cessie S, et al. Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study. BMJ. 2009;8;338:a3083.) |
302 participants of the Leiden-85 study, aged 85 years, 71.1% females. Follow-up was 5 years |
The classic risk factors, including TC and HDL-C, were not predictors of cardiovascular mortality when used in Framingham's risk score, with a relative risk of 1.2 (CI: 0.51-2.6). CRP and IL6 were not cardiovascular mortality predictors, with p = 0.68 and 0.44, respectively |
Carriere et al., 2008(1818. Carriere I, Dupuy AM, Lacroux A, Cristol J P, Delcourt C. Pathologies Oculaires Liées à l'Age Study Group Biomarkers of inflammation and malnutrition associated with early death in healthy elderly people. J Am Geriatr Soc. 2008;56(5):840-6.) |
1,441 participants with mean age of 70 years and standard deviation of 6.6 years. Of these,134 were over 80 years old, 38% of them, males |
Elevated CRP was associated with total, early, and late mortality in both genders, but with statistical significance only in males. HDL-C was not analyzed |
Berbée et al., 2008(1919. Berbée JFP, Mooijaart S P, Craen AJM, Havekes LM, Heemst D, Rensen PCN, Westerdorn RGJ. Plasma apolipoprotein CI protects against mortality from infection in old age. J Gerontol Series A. 2008;63(2):122-6.) |
561 participants, all of them 85 years old |
A high level of apoC1 was associated with mortality due to all causes. Both HDL-C and CRP showed a significant positive association with apoC1 |
Clarke et al., 2008(2020. Clarke R, Emberson JR, Breeze E, Casas J P, Parish S, Hingorani AD, et al. Biomarkers of inflammation predict both vascular and non-vascular mortality in older men. Eur Heart J. 2008;29(6):800-9.) |
5,360 male participants, with a mean age of 76.9 years, range of 66-96 years |
CRP and the TC/HDL-C ratio showed a significant positive association with vascular and non-vascular mortality |
Landi et al., 2008(2121. Landi F, Russo A, Pahor M, Capoluongo E, Liperoti R, Cesari M, et al. Serum high-density lipoprotein cholesterol levels and mortality in frail, community-living elderly. Gerontology. 2008;54(2):71-8.) |
359 elderly subjects, all over 80 years of age, with a mean age of 85.9 years. 67% were females. Analysis was performed during a two-year period |
HDL-C showed an inverse relation with mortality. Comparing the third with the highest HDL-C (> 45.1mg/dL for men and 51.1 mg/dL for women) with that of the lowest HDL-C (< 38mg/dL and < 41mg/dL for men and women, respectively), the HR was 0.41, CI: 0.21-0.79, similar between genders, and maintaining statistical significance after analysis of the indicators of fragility and albumin |
Akerblom et al., 2008(2222. Akerblom JL, Costa R, Luchsinger JA, Manly JJ, Tang MX, Lee JH, et al. Relation of plasma lipids to all-cause mortality in caucasian, african-american and hispanic elders. Age Ageing. 2008;37(2):207-13.) |
2,556 subjects were analyzed, with a mean age of 77 years, range of 65 - 103 years. Of these, 27.6% were Caucasian, 31.2% Afro-American, and 41.2% Hispanic |
The highest levels of HDL-C were obtained among Afro-Americans, which also presented with highest mortality rates. However, there was no significant association between HDL-C and mortality |
Kompoti et al., 2008(2323. Kompoti M, Drimis S, Papadaki A, Kotsomytis K, Poulopoulou C, Gianneli D, et al. Serum C-reactive protein at admission predicts in-hospital mortality in medical patients. Eur J Intern Med. 2008;19(4):261-5.) |
382 patients admitted to a ward during the period of 6 months. Mean age was 70.8 ± 15.7 years, and the main cause of hospitalization was stroke |
CRP was greatest in patients that died, with p < 0.001, increasing with age. Among those older than 80 years, CRP was predictive of hospital mortality, with a HR: 5.41 and p = 0.01 |
Shinkai et al., 2008(2424. Shinkai S, Chaves PH, Fujiwara Y, Watanabe S, Shibata H, Yoshida H, et al. Beta2-microglobulin for risk stratification of total mortality in the elderly population: comparison with cystatin C and C-reactive protein. Arch Intern Med. 2008;28;168(2):200-6.) |
1,034 elderly Japanese subjects, age range of 65-89 years, and mean follow-up of 7.9 years |
Participants were divided into 3 groups as per level of CRP. The group with intermediate levels of CRP displayed HR for mortality of 1.39, with CI: 0.98-1.98, and the group with elevated CRP had a HR of 1.44, with a CI: 1-2.06 |
Spada et al., 2007(2525. Spada RS, Toscano G, Cosentino FI, Iero I, Lanuzza B, Tripodi M, et al. Low total cholesterol predicts mortality in the nondemented oldest old. Arch Gerontol Geriatr. 2007;44 Suppl 1:381-4.) |
23 residents of a rural area, all aged between 85 and 94 years, 65% of them males, were analyzed for 2 years |
Total cholesterol varied from 116 to 239 mg/dL. Assessing 4 variables (gender, BMI, age, and total cholesterol), only the low level of TC (<160mg/dL) showed a significant relationship with mortality, with p < 0.002. |
Dupuy et al., 2007(2626. Dupuy AM, Jaussent I, Lacroux A, Durant R, Cristol J P, Delcourt C. Waist circumference adds to the variance in plasma C-reactive protein levels in elderly patients with metabolic syndrome. Gerontology. 2007;53(6):329-39.) |
1,709 participants with a mean age of 69.3 years, range of 60-92.9 years. Of these, 169 were over 80 years of age, and 38% were males |
CRP showed no statistical difference between genders. Comparing the quartiles with the highest and lowest levels of CRP (> 3.05 and < 0.82mg/L), there was a significant relationship with metabolic syndrome. Analyzing HDL-C < 40 mg/dL for men or < 50mg/dL for women, the OR for the prevalence of the metabolic syndrome was 1.6 in women, with a CI: 1.03-2.48, and there was no statistical significance among the men |
Jylha et al., 2007(2727. Jylhä M, Paavilainen P, Lehtimäki T, Goebeler S, Karhunen PJ, Hervonen A, et al. Interleukin-1 receptor antagonist, interleukin-6, and C-reactive protein as predictors of mortality in nonagenarians: the vitality 90+ study. J Gerontol A Biol Sci Med Sci. 2007;62(9):1016-21.) |
285 nonagenarians were accompanied for a period of 4 years |
Both HDL-C and CRP were greater in survivors, with an inverse relationship between HDL-C and CRP with statistical significance (p < 0.001). CRP also presented a positive relationship with mortality, but with no statistical significance after adjustment for all D70 variables |
Mooijaart et al., 2006(2828. Mooijaart S P, van Vliet P, van Heemst D, Rensen PC, Berbée J F, Jolles J, et al. Westendorp RG. Plasma levels of apolipoprotein E and cognitive function in old age. Ann N Y Acad Sci. 2007;1100:148-61) |
546 elderly individuals, all aged 85 years |
HDL-C showed an inverse relation with APOE4 and with cardiovascular mortality. CRP also showed a significant positive relation with APOE4 and with cardiovascular mortality, with the risk of cardiovascular mortality related to APOE4 dependent on CRP+D77 |
Kistorp et al., 2005(2929. Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA. 2005;293(13):1609-16.) |
626 participants with a mean age of 67.9 years, range of 50-89 years, were evaluated for a period of 5 years |
The group formed by 20% of the participants with highest levels of CRP showed a positive relationships with mortality, with a HR: 1.46, but no statistical significance, p = 0.14 |
Schupf et al., 2005(3030. Schupf N, Costa R, Luchsinger J, Tang MX, Lee JH, Mayeux R.0. Relationship between plasma lipids and all-cause mortality in nondemented elderly. J Am Geriatr Soc. 2005;53(2):219-26.) |
2,277 elderly subjects with no cognitive deficit and a mean age of 76 years, range of 65-98 years, 65.6% of them females. Mean follow-up of 3 years, with a standard deviation of 2.5 years |
HDL-C displayed no statistical relation+D87 with mortality. Participants over 75 years of age had higher HDL-C levels than those younger than 75 years, with p < 0.05 |
Psaty et al., 2004(3131. Psaty BM, Anderson M, Kronmal RA, Tracy R P, Orchard T, Fried L P, et al. The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study. J Am Geriatr Soc. 2004;52(10):1639-47.) |
4,885 elderly individuals, over 65 years of age, and mean age of 73 ± 5.7 years for men and 72.3 ± 5.3 years for women, 60% of them females. Mean follow-up was 7.5 years |
HDL-C showed an inverse relation with the risk of AMI in both genders, with a HR:0.85 and CI: 0.76-0.96. This relation is more important in the <75 years of age group. HR: 0.75 versus 0.95 in those older than 75 years. As to the ischemic stroke+D144 outcome, HDL-C showed an inverse relation+D171 in men, with a HR: 0.74, but not in women (HR:1). There was no interaction with CRP (p = 0.61) nor a significant relation+D102 with total mortality |
Weverling-Rijnsburger et al,. 2003(3232. Weverling-Rijnsburger AW, Jonkers IJ, van Exel E, Gussekloo J, Westendorp RG. High-density vs low-density lipoprotein cholesterol as the risk factor for coronary artery disease and stroke in old age. Arch Intern Med. 2003;163(13):1549-54.) |
599 participants of the Leiden 85-Plus study. All over 85 years of age, 67% of them females. Mean follow-up was 2.6 years |
The primary cause of death was cardiovascular, with results similar at all levels of LDL-C, but with relative risk for fatal cardiovascular disease of 2 for the group with lowest levels of HDL-C, a relative risk of 2 for CAD, and of 2.6 for cerebrovascular accident |
Lloyd-Jones et al., 2003(3333. Lloyd-Jones DM, Wilson PW, Larson MG, Leip E, Beiser A, D'Agostino RB, et al. Lifetime risk of coronary heart disease by cholesterol levels at selected ages. Arch Intern Med. 2003;163(16):1966-72.) |
7,288 participants of the “Framingham Heart Study” in which 55% were females, age range of 40- 94 years |
In the 80-years-of-age bracket, dividing the participants into 3 subgroups according to the levels of HDL-C, the risk of developing CAD was 19.4 and 12.7% in the third with the highest level of HDL-C, 18.8 and 20.1% in the intermediate subgroup, and 40.4 and 20.9% in those with lowest levels of HDL-C, in men and women, respectively. Considering the TC/HDL-C index, results showed a risk of 16.3 and 0% in the group with the smallest index, 18.6 and 18.5% in the intermediate group, and 36.2 and 21.9% in those with the highest indices, among men and women, respectively |
Shor et al., 2008(3434. Shor R, Wainstein J, Oz D, Boaz M, Matas Z, Fux A, Halabe A. Low HDL levels and the risk of death, sepsis and malignancy. Clin Res Cardiol. 2008;97(4): 227-33.) |
204 patients hospitalized during the year 2005, were divided into two groups, as per HDL-C. Group 1 (HDL-C < 20mg/dL) with a mean age of 66.6 years and a standard deviation of 18.9 years, and Group 2 (HDL-C >6 5 mg/dL) with a mean age of 66.3 years and a standard deviation of 16.9 years |
Group 1 presented an OR: 17.5 for mortality (p < 0.0001), OR: 15 for fever or SEPSIS (p < 0.0001), and OR: 6.7 for the development of malignancies (p = 0.004). |
Yokohawa et al., 2008(3535. Yokokawa H, Goto A, Terui K, Funami Y, Watanabe K, Yasumura S. Prevalence of metabolic syndrome and serum marker levels in patients with four subtypes of cerebral infarction in Japan. J Clin Neurosci. 2008;15(7):769-73) |
171 patients diagnosed with stroke, ages 36 to 96 years. The patients were subdivided into 4 etiological subtypes and analyzed as to markers of fibrinolysis and atherosclerosis |
The level of HDL-C varied significantly among the subtypes of cerebrovascular accidents, with a mean of 37.8 mg/dL for the embolic type, 40.2 mg/dL for the atherothrombotic type, 47mg/dL in the lacunar type, and 48.2 mg/dL in the TIA, with p < 0.05. Embolic cerebrovascular accident present with the worst prognosis, with the greatest disability and time of hospitalization. CRP showed no statistical significance |
Fujisawa et al., 2008(3636. Fujisawa M, Okumiya K, Matsubayashi K, Hamada T, Endo H, Doi Y. Factors associated with carotid atherosclerosis in community-dwelling oldest elderly aged over 80 years. Geriatr Gerontol Int. 2008;8(1):12-8.) |
136 longevous elderly individuals aged over 80 years were evaluated for carotid atherosclerosis. Mean age was 84 years, and 39% were males. Factors related to atherosclerosis were analyzed by multiple regression |
HDL-C was significantly higher in women, while the thickness of the intima layer of the carotid was greater in men. There was no significant difference between the HDL-C of the group with less and with more than 1 mm of carotid intima layer thickness |
Flegar-Meštrić et al., 2007(3737. Flegar-Mestrić Z, Vrhovski-Hebrang D, Preden-Kereković V, Perkov S, Hebrang A, Grga A, et al. C-reactive protein level in severe stenosis of cerebral arteries. Cerebrovasc Dis. 2007;23(5-6):430-4.) |
119 patients with carotid insufficiency and stenosis were investigated, with a mean age of 66 years in the group with stenosis less than 70%, and of 68 years in the group with stenosis greater than 70%, age range of 41-83 years |
Comparing the group without stenosis with the two other groups, HDL-C showed a significant association with carotid stenosis, but comparing the two groups with stenosis, there was no statistical significance. As to CRP, there was a significant association with carotid stenosis, and statistical significance was lost only when compared to the groups with stenosis of less than 70% with the controls. There was a positive relation between the CRP and the total cholesterol/HDL-C ratio in the group with stenosis >70% |
Rontu et al., 2006(3838. Rontu R, Ojala P, Hervonen A, Goebeler S, Karhunen PJ, Nikkilä M, et al. T. Apolipoprotein E genotype is related to plasma levels of C-reactive protein and lipids and to longevity in nonagenarians. Clin Endocrinol (Oxf). 2006;64(3):265-70.) |
291 nonagenarians were analyzed comparing them with 3 other populations as controls, involving newborns, a cohort of 40 years and another of 70 years |
HDL-C showed no association with the ApoE genotype. Elevated CRP was positively associated with the ε2/3 genotype and inversely associated with ε3/4, with statistical significance when comparing only the 3 most common genotypes. Apoε4 has an inverse relation with longevity |
Lehtimaki et al., 2005(3939. Lehtimäki T, Ojala P, Rontu R, Goebeler S, Karhunen PJ, Jylhä M, et al. Interleukin-6 modulates plasma cholesterol and C-reactive protein concentrations in nonagenarians. J Am Geriatr Soc. 2005;53(9):1552-8.) |
291 nonagenarians were analyzed and compared to a group of 227 healthy adults with a mean age of 44 years. 20% were males |
Nonagenarians had the highest levels of IL6 and CRP (p < 0.001). As per the quartile of IL6, the levels of CRP (p < 0.001) were higher and of HDL-C (p = 0.002) were lower. These associations were not found in young adults |
Hoekstra et al.,2005(4040. Hoekstra T, Geleijnse JM, Schouten EG, Kok FJ, Kluft C. Relationship of C-reactive protein with components of the metabolic syndrome in normal-weight and overweight elderly. Nutr Metab Cardiovasc Dis. 2005;15(4):270-8.) |
605 participants with a mean age of 73 years for men and 74 years for women, age range of 65-84 years |
In participants with BMI < 25 kg/m2, the CRP had a negative association with HDL-C (p < 0.001). However, in participants with BMI > 25 kg/m2, statistical significance is lost |