| Amarenco et al. 2008*(11) |
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**(12) |
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***(13) |
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***(14) |
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***(15) |
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***(16) |
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***(17) |
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***(18) |
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***(19) |
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***(20) |
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***(21) |
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***(22) |
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***(23) |
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***(24) |
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***(25) |
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***(26) |
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***(27) |
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***(28) |
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***(29) |
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***(30) |
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***(31) |
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***(32) |
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***(33) |
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#(34) |
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##(35) |
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##(36) |
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##(37) |
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##(38) |
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##(39) |
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##(40) |
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 |
The importance of HDL-C and CRP in cardiovascular risk evaluation in longevous elderly individuals