Non-linear Relationship Between Plasma Amyloid-ß 40 Level and Cognitive Decline in a Cognitively Normal Population.

OBJECTIVES: Recent studies regarding the relationships between plasma amyloid-ß (Aß) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aß levels in a large-sample cognitively normal population. METHODS: This population-based, prospective cohort study included 1,240 participants with normal cognition. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and 2 years later. Restricted cubic splines, multivariate logistic regression, and multivariate linear regression models were used to evaluate the type of relationship between cognitive decline during the 2-year follow-up period and plasma Aß levels (Aß40, Aß42, and Aß42 / 40). RESULTS: Participants with moderate Aß40 levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low Aß40 [odds ratio (OR): 0.60, 95% confidence interval (CI): 0.45-0.81, p < 0.001] or high Aß40 (OR: 0.65, 95% CI: 0.49-0.87, p = 0.004) levels. The association between Aß40 and cognitive decline did not depend on sex, education level, or APOE ε4 status. There was an interaction found between age (≤ 65 and > 65 years) and Aß40 (p for interaction = 0.021). In individuals older than 65 years, there was a positive linear relationship between plasma Aß40 and cognitive decline (OR: 1.02, 95% CI: 1.00-1.04, p = 0.027). For participants ≤ 65 years old, the lower Aß40 and higher Aß40 groups had a lower risk of cognitive decline than the medium Aß40 group (OR: 0.69, 95% CI: 0.50-0.94, p = 0.02; OR: 0.63, 95% CI: 0.45-0.86, p = 0.004). None of relationship between plasma Aß42, Aß42 / 40 and cognitive decline was found during a 2-year follow-up. CONCLUSION: The relationship between plasma Aß40 and cognitive decline was not linear, but an inverted-U shape in a cognitively normal population. The underlying mechanism requires further investigation.

Relationship Between Peripheral Transport Proteins and Plasma Amyloid-ß in Patients with Alzheimer's Disease Were Different from Cognitively Normal Controls: A Propensity Score Matching Analysis.

BACKGROUND: Transport proteins, soluble LRP1 (sLRP1) and soluble RAGE (sRAGE), play a pivotal role in the peripheral clearance of plasma amyloid-ß (Aß). However, their relationship is seldom discussed, especially in Alzheimer's disease (AD). OBJECTIVE: To explore whether their relationship in patients with AD varied from those in cognitively normal (CN) controls. METHODS: We initially recruited 70 patients with AD and 725 CN controls, then applied propensity score matching (PSM) analysis to balance the differences between two groups. Plasma levels of sLRP1, sRAGE, and Aß were measured using commercial ELISA kits and log transformed when skewed distributed. The relationship between sLRP1/sRAGE and plasma Aß were analyzed using Pearson's correlation analysis followed by multiple linear regression separately in the original population and matched participants. RESULTS: After PSM, 70 patients with AD and 140 matched controls were included for further analysis. Log sLRP1 was positively correlated with plasma Aß40 in matched CN controls (r = 0.222, p = 0.008) but not in patients with AD (r = 0.137, p = 0.260). After multivariable adjustment, Log sLRP1 remained significantly associated with plasma Aß40 in the CN group (ß= 7.347, p = 0.014) but not in the AD group (ß= 10.409, p = 0.105). In contrast, Log sLRP1 was not correlated with plasma Aß42 in patients with AD or CN controls, and Log sRAGE was consistently not associated with plasma Aß40 or Aß42 in either group. CONCLUSION: The significant correlation between sLRP1 and plasma Aß40 present in CN controls was not found in patients with AD, suggesting that their relationship was different in AD. However, the specific mechanisms and its influence on cerebral amyloid burden require further validation.

The relationship between blood lipids and plasma amyloid beta is depend on blood pressure: a population-based cross-sectional study.

BACKGROUND: It is believed that deposition of amyloid beta (Aß) in the brain is the central pathological changes of Alzheimer's disease (AD), which triggers a series of pathological processes. However, the relationship between dyslipidemia and AD is uncertain. Considering the peripheral Aß levels are related to brain Aß deposition, we explore the relationships between blood lipids and plasma Aß. METHODS: Participants who lived in the selected village of Xi'an for more than 3 years were enrolled, aged 40-85 years (n = 1282, 37.9% male). Fasting blood lipid, plasma Aß levels, basic information and living habits were measured. Multiple linear regressions were used. RESULTS: In total population, blood lipids were not associated with plasma Aß. After stratified by blood pressure, serum total cholesterol (TC) and low-density lipoprotein (LDL-c) were positively associated with plasma Aß42 levels (ßTC = 0.666, PTC = 0.024; ßLDL-c = 0.743, PLDL-c = 0.011, respectively) in normal blood pressure. LDL-c was negatively associated with plasma Aß40 levels (ß = - 0.986, P = 0.037) in high blood pressure. CONCLUSION: Elevated plasma Aß42 levels are associated with higher TC and LDL-c in normal blood pressure. Elevated plasma Aß40 levels are associated with lower LDL-c in high blood pressure. This indicated that the relationships between blood lipids and plasma Aß were confounded by blood pressure.

The gender- and age- dependent relationships between serum lipids and cognitive impairment: a cross-sectional study in a rural area of Xi'an, China.

BACKGROUND: Serum lipids [total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG)] are risk factors for stroke, but the relationships between serum lipids and cognitive impairment have not been verified completely. In this study, we studied the relationships between serum lipids and cognitive impairment and explored whether gender and age had effects on the relationships. METHODS: In this cross-sectional study, we collected serum lipids and cognitive function information from 1762 participants (aged 40-85). Univariate analysis, multivariate analysis, and both gender- and age-based stratified multivariate analysis were used. RESULTS: In the entire sample set, there was no significant correlation between serum lipid parameters (TC, LDL-C, HDL-C and TG) and cognitive impairment. In both gender- and age-based stratified multivariate analysis, high serum TC was positively associated with cognitive impairment in the elderly (> 55) male participants (OR = 4.404, 95% CI = 1.264-15.344, p = 0.02), and high serum LDL-C was positively correlated with cognitive impairment in the elderly female subjects (OR = 2.496, 95% CI = 1.057-5.896, p = 0.037), while high serum TG was negatively associated with cognitive impairment in the middle-aged (≤ 55) male participants (OR = 0.157, 95% CI = 0.051-0.484, p = 0.001). CONCLUSIONS: The relationships between serum lipids and cognitive impairment are gender- and age- dependent, with high serum TC and LDL-C may be risk factors of cognitive impairment in the elderly male and female subjects respectively, while high serum TG may be protector of cognitive impairment in the middle-aged male participants.

The Level of Plasma Amyloid-ß40 Is Correlated with Peripheral Transport Proteins in Cognitively Normal Adults: A Population-Based Cross-Sectional Study.

BACKGROUND: Transport proteins, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), and soluble receptor of advanced glycation end products (sRAGE), play an important role in the clearance of plasma amyloid-ß (Aß). However, their relationship is not clear. OBJECTIVE: The aim was to explore the relationship between plasma levels of sLRP1, sRAGE, and Aß in a cross-sectional study. METHODS: A total of 1,185 cognitively normal participants (age above 40) from a village in the suburbs of Xi'an, China were enrolled from October 8, 2014 to March 30, 2015. Plasma Aß40, Aß42, sLRP1, and sRAGE were tested using a commercial ELISA. Apolipoprotein E (APOE) genotyping was conducted using PCR and sequencing. The relationship between plasma levels of sLRP1, sRAGE, and Aß was analyzed using Pearson's correlation analysis and multiple linear regression. RESULTS: In the total population, Log sLRP1 and Log sRAGE were positively correlated with plasma Aß40 (r= 0.103, p < 0.001; r= 0.064, p = 0.027, respectively), but neither were associated with plasma Aß42. After multivariable adjustment in the regression model, Log sLRP1 and Log sRAGE were still positively related with plasma Aß40 (ß= 2.969, p < 0.001; ß= 1.936, p = 0.017, respectively) but not Aß42. Furthermore, the positive correlations between transport proteins and plasma Aß40 remained significant only in APOEɛ4 non-carriers after Pearson's analysis and multiple regression analysis after stratification by gene status. CONCLUSION: The concentrations of plasma sLRP1 and sRAGE had a significant impact on the level of plasma Aß40 in cognitively normal adults, especially in APOEɛ4 non-carriers. However, the mechanism by which the transport proteins are involved in peripheral Aß clearance and the relationship between transporters and amyloid burden in the brain needs further validation.

Elevation of Plasma Amyloid-ß Level is More Significant in Early Stage of Cognitive Impairment: A Population-Based Cross-Sectional Study.

BACKGROUND: Aggregation and deposition of amyloid-ß (Aß) in the brain is the main pathological change of Alzheimer's disease (AD). Decreased Aß42 in the cerebrospinal fluid has been confirmed as a biomarker of AD; however, the relationship between plasma Aß and cognitive impairment is currently unclear. OBJECTIVE: The aim was to explore the relationship between plasma Aß and cognitive impairment in a cross-sectional study. METHODS: A total of 1,314 subjects (age above 40) from a village in the suburbs of Xi'an, China were enrolled between October 8, 2014 and March 30, 2015. A validated Chinese version of the Mini-Mental State Examination and neuropsychological battery were used to assess cognition. Levels of plasma Aß42 and Aß40 were tested using commercial enzyme-linked immunosorbent assay. Relationship of plasma Aß and cognitive impairment was analyzed using logistic regression analysis. RESULTS: Of the enrolled subjects, 1,180 (89.80%) had normal cognition, 85 (6.47%) had possible cognitive impairment and 49 (3.73%) had probable cognitive impairment. Logistic regression analysis showed that the Aß42/Aß40 ratio (OR = 4.042, 95% CI: 1.248-11.098, p = 0.012) and plasma Aß42 (OR = 1.036, 95% CI: 1.003-1.071, p = 0.031) was higher in the possible cognitive impairment than that in the normal cognition group. Furthermore, the plasma Aß42/Aß40 ratio was higher in the possible cognitive impairment group than that in the probable cognitive impairment group (OR = 0.029, 95% CI: 0.002-0.450, p = 0.011). CONCLUSIONS: Levels of plasma Aß42 and Aß42/Aß40 ratio were elevated in patients with possible cognitive impairment, indicating that plasma Aß42 and Aß42/Aß40 ratio increases may be more pronounced in early stage of cognitive impairment.

Pulse pressure is associated with plasma amyloid-ß transport dysfunction.

OBJECTIVE: Increased pulse pressure (PP) has been implicated in the development and progression of Alzheimer's disease in middle-aged and elderly adults. Considering the close relationship between peripheral amyloid-ß clearance and brain amyloid-ß deposition, we investigated the potential association between PP and plasma amyloid-ß transport function. METHODS: In this cross-sectional study, a total of 1118 participants underwent a health assessment and quantification of plasma amyloid-ß and amyloid-ß transporter expression. Relationships between plasma levels of amyloid-ß1-40, amyloid-ß1-42, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), soluble receptor for advanced glycation end products (sRAGE), and PP were determined using multiple linear regressions. RESULTS: PP was a significant determinant of amyloid-ß1-40 level (ß = 0.059, P = 0.036) and log-transformed sRAGE (ß = -0.002, P = 0.029) independent of age, sex, body mass index, pulse rate, mean arterial pressure, blood glucose, blood lipids, lifestyle, and medical history. Additionally, log-transformed soluble low-density lipoprotein receptor-related protein-1 and log-transformed sRAGE were positively associated with plasma amyloid-ß1-40 level (ß = 3.610, P < 0.001; ß = 2.573, P = 0.001). Similar associations were observed between log-transformed sRAGE and plasma amyloid-ß1-42 level (ß = 1.350, P = 0.022). CONCLUSION: An elevation in PP is associated with increased plasma amyloid-ß1-40 and decreased log-transformed sRAGE among individuals not taking antihypertensive medication. The underlying mechanism of this effect may be relevant to peripheral amyloid-ß clearance.

Asociación entre el tabaquismo actual y el deterioro cognitivo y su relación con la edad: estudio transversal realizado en Xi’an (China) / Association between current smoking and cognitive impairment depends on age: A cross-sectional study in Xi’an, China

Antecedentes: El consumo de tabaco es un factor de riesgo modificable para el deterioro cognitivo, no entendiéndose plenamente la relación entre dichas situaciones. El objetivo de este trabajo fue identificar la posible asociación entre el consumo actual de tabaco y el deterioro cognitivo, dependiendo de la edad, en la población rural de China. Métodos: El estudio incluyó a 1.782 participantes (de 40 años de edad o más) que vivían en un pueblo rural de las cercanías de Xi’an (China). Se recogieron datos acerca del historial de consumo de tabaco y la función cognitiva. La función cognitiva se puntuó mediante la escala Mini-Mental State Examination. El efecto de la edad en la relación entre el consumo de tabaco actual y el deterioro cognitivo se analizó mediante análisis de interacción y estratificación, utilizando modelos de regresión logística. Resultados: El análisis de interacción reflejó que el consumo de tabaco actual guarda una relación positiva con el deterioro cognitivo (odds ratio [OR]=9,067; intervalo de confianza del 95% [IC 95%] 1,3056-2,979; p=0,026). Sin embargo, el plazo de interacción y la edad del tabaquismo actual guardan una relación negativa con el deterioro cognitivo (OR=0,969; IC 95% 0,939-0,999; p=0,045). La regresión logística estratificada reflejó que en el subestrato de 40 a 65 años, la OR del tabaquismo actual es de 1,966 (p=0,044), mientras que en el subestrato > 65 años, la OR es de 0,470 (p=0,130). Esto significa que la asociación entre el tabaquismo actual y el deterioro cognitivo con la edad podría ser positiva (OR>1) en los subestratos de menor edad, aunque no existe una diferencia significativa en subestratos de mayor edad. Conclusiones: En conclusión, el tabaquismo actual podría estar positivamente asociado al deterioro cognitivo en la edad mediana, aunque dicha relación disminuye con el incremento de la edad (AU)

Background: Cigarette smoking is a modifiable risk factor for cognitive impairment, while the relationship between current smoking and cognitive impairment is not fully understood. The objectives were to identify a possible association between current smoking and cognitive impairment depending on age in the Chinese rural population. Methods: Data for the study consisted of 1,782 participants (40 years and older) who lived in a rural village in the vicinity of Xi’an, China. Data about smoking history and cognitive function were collected. Cognitive function was scored by the Mini-Mental State Examination. The effect of age on the relationship between current smoking and cognitive impairment was analyzed with interaction and stratified analysis by logistic regression models. Results: Interaction analysis showed that current smoking is positively related with cognitive impairment (odds ratio [OR]=9.067; 95% confidence interval [95% CI] 1.305-62.979; P=.026). However, the interaction term, age by current smoking, is negatively related with cognitive impairment (OR=0.969; 95%CI 0.939-0.999; P=.045). Stratified logistic regression showed that in the 40-65 years of age sublayer, OR of current smoking is 1.966 (P=.044), whereas in the>65 years of age sublayer, the OR is 0.470 (P=.130). This means that the association between current smoking and cognitive impairment with age might be positive (OR>1) in lower age sublayers, but no significant difference in higher age sublayers. Conclusions: In conclusion, current smoking might be positively associated with cognitive impairment in the middle-aged but the relationship declines with increasing age (AU)

Association between current smoking and cognitive impairment depends on age: A cross-sectional study in Xi'an, China. / Asociación entre el tabaquismo actual y el deterioro cognitivo y su relación con la edad: estudio transversal realizado en Xi'an (China).

BACKGROUND: Cigarette smoking is a modifiable risk factor for cognitive impairment, while the relationship between current smoking and cognitive impairment is not fully understood. The objectives were to identify a possible association between current smoking and cognitive impairment depending on age in the Chinese rural population. METHODS: Data for the study consisted of 1,782 participants (40 years and older) who lived in a rural village in the vicinity of Xi'an, China. Data about smoking history and cognitive function were collected. Cognitive function was scored by the Mini-Mental State Examination. The effect of age on the relationship between current smoking and cognitive impairment was analyzed with interaction and stratified analysis by logistic regression models. RESULTS: Interaction analysis showed that current smoking is positively related with cognitive impairment (odds ratio [OR]=9.067; 95% confidence interval [95% CI] 1.305-62.979; P=.026). However, the interaction term, age by current smoking, is negatively related with cognitive impairment (OR=0.969; 95%CI 0.939-0.999; P=.045). Stratified logistic regression showed that in the 40-65 years of age sublayer, OR of current smoking is 1.966 (P=.044), whereas in the>65 years of age sublayer, the OR is 0.470 (P=.130). This means that the association between current smoking and cognitive impairment with age might be positive (OR>1) in lower age sublayers, but no significant difference in higher age sublayers. CONCLUSIONS: In conclusion, current smoking might be positively associated with cognitive impairment in the middle-aged but the relationship declines with increasing age.

The Age-Dependent Relationship between Blood Pressure and Cognitive Impairment: A Cross-Sectional Study in a Rural Area of Xi'an, China.

BACKGROUND: Hypertension is a modifiable risk factor for cognitive impairment, although the relationship between hypertension and cognitive impairment is not fully understood. The objective of this study was to investigate the effect of age on the relationship between blood pressure and cognitive impairment. METHODS: Blood pressure and global cognitive function information was collected from 1799 participants (age 40-85) who lived in a village in the suburbs of Xi'an, China, during in-person interviews. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score lower than the cutoff value. The effect of age on the relationship between blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), and high blood pressure (HBP, SBP≥140 mm Hg and/or DBP≥90 mm Hg)] and cognitive impairment was analyzed by logistic regression models using interaction and stratified analysis. Blood pressure and age were regarded as both continuous and categorical data. RESULTS: A total of 231 participants were diagnosed as having cognitive impairment based on our criteria. Interaction analysis for the total population showed that SBP (when regarded as continuous data) was positively correlated with cognitive impairment (OR = 1.130 [95% CI, 1.028-1.242] per 10mmHg, P = 0.011); however, the age by SBP interaction term was negatively correlated with cognitive impairment (OR = 0.989 [95% CI, 0.982-0.997] per 10mmHg×year, P = 0.006), indicating that the relationship between SBP and cognitive impairment was age-dependent (OR = 1.130×0.989(age-55.5) per 10mmHg,40 ≤age≤85). When the blood pressure and age were considered as binary data, the results were similar to those obtained when they were considered as continuous variables. Stratified multivariate analysis revealed that the relationship between SBP (when regarded as continuous data) and cognitive impairment was positive for patients aged 40-49 years (OR = 1.349 [95% CI: 1.039-1.753] per 10mmHg, P = 0.025) and 50-59 years (OR = 1.185 [95% CI: 1.028-1.366] per 10mmHg, P = 0.019), whereas it tended to be negative for patients aged 60-69 years (OR = 0.878 [95% CI: 0.729-1.058] per 10mmHg, P = 0.171) and ≥70 years (OR = 0.927 [95% CI: 0.772-1.113] per 10mmHg, P = 0.416). Results similar to those for SBP were obtained for DBP, MABP and HBP as well. Subsequently, SBP, DBP and MABP were transformed into categorical data (SBP<140mmHg, 140mmHg≤SBP<160mmHg, and SBP≥160mmHg; DBP<90mmHg, 90mmHg≤DBP<100mmHg, and DBP≥100mmHg; MABP<100mmHg, 100mmHg≤MABP<110mmHg, and MABP≥110mmHg), and the stratified multivariate analysis was repeated. This analysis showed that the age-dependent association continued to exist and was especially prominent in the SBP≥160 mmHg, DBP≥90 mmHg and MABP≥110 mmHg groups. CONCLUSIONS: Elevated blood pressure is positively correlated with cognitive impairment in the middle-aged, but this positive association declines with increasing age. These results indicated that specific blood pressure management strategies for various age groups may be crucial for maintaining cognitive vitality.

Association between Carotid Intima-Media Thickness and Cognitive Impairment in a Chinese Stroke Population: A Cross-sectional Study.

This study aimed to investigate the potential associations between carotid intima-media thickness and cognitive impairment among patients with acute ischemic stroke and to identify the clinical implications. We measured carotid intima-media thickness (IMT) and performed the Mini-Mental State Examination (MMSE) upon the admission of 1,826 acute ischemic stroke patients. The association between IMT and cognitive impairment evaluated by the MMSE was assessed with a multivariate regression analysis. Other clinical variables of interest were also assessed. After adjusting for potential confounders, participants in the highest IMT quartile had a higher likelihood of having cognitive impairments compared with the lowest IMT quartile (odds ratio: 3.01, 95% confidence interval: 2.07-4.37, p < 0.001). Stratified analyses indicated that this positive correlation was similar for the maxIMT and meanIMT of carotid artery measurements. A positive correlation was found between IMT and cognitive impairment in participants with acute ischemic stroke.

[Investigation on plasma homocysteine level and cognition in population at high risk for stroke in Xi'an].

OBJECTIVE: To investigate the relationship between plasma homocysteine (Hcy) and cognitive impairment so as to provide basis for dementia prevention. METHODS: Subjects at high risk for stroke were selected from the Screening and Prevention Program of Stroke (organized by the Ministry of Health, from August to December, 2012) in Yanta area, Xi'an. Fasting blood was taken from cubital vein to measure Hcy. When Hcy>15 µmol/L was defined as hyperhomocysteinemia, Hcy in the range of 16-30 µ mol/L was considered mild, ≥ 31 µ mol/L as moderate-severe hyperhomocysteinemia. The cognitive function was evaluated by the Mini Mental State Examination (MMSE). MMSE grades under normal value were defined as cognitive impairment. RESULTS: 393 subjects were randomly recruited, including 173 men (44.0%) and 220 women (56.0%). Number of cases with cognitive impairment was 70 (17.8% of the total subjects), with hyperhomocysteinemia was 220 (56.0% of the total subjects). The prevalence of cognitive impairment did not show significant difference with hyperhomocysteinemia or normal Hcy group (16.8% vs. 19.1%, P>0.05), neither with mild and moderate-severe hyperhomocysteinemia group (17.0% vs. 16.3% , P > 0.05). Results from Spearman correlation analysis indicated that there was no correlation between MMSE grades and Hcy (rs = -0.01, P = 0.85). Prevalence of cognitive impairment in the smoking group was higher than that in the non-smoking group (21.3% vs. 7.8%, P < 0.01), but higher in hypertension group than that in the normal blood pressure group (21.7% vs. 8.0%, P < 0.01). In the stroke group, prevalence of cognitive impairment was seen higher than that in the non-stroke group (25.3% vs. 15.4%, P < 0.05). Based on the results from Binary logistic regression, cognitive impairment appeared to be associated with the levels of education (OR = 0.90, 95% CI:0.81-0.98, P = 0.02), histories of hypertension (OR = 1.02, 95%CI:1.01-1.04, P = 0.01) and stroke(OR = 1.86, 95%CI:1.04-3.33, P = 0.04), but there was no correlation seen between Hcy and cognitive impairment (OR = 0.90, 95% CI:0.51-1.58, P = 0.71). CONCLUSION: Plasma homocysteine did not seem a risk factor for cognitive impairment.

Plasma lipoprotein(a) indicates risk for 4 distinct forms of vascular disease.

BACKGROUND: Increased lipoprotein(a) [Lp(a)] concentrations are predictive for coronary artery disease (CAD). The risk conferred by Lp(a) for other types of vascular disease compared with CAD has not been investigated within a single population. This study aimed to investigate Lp(a) risk association for 4 different types of vascular disease (including CAD) within a predominantly white population. METHODS: We used an Lp(a) ELISA that measures Lp(a) independently of apolipoprotein(a) size to measure plasma Lp(a) in patients [384 CAD, 262 peripheral vascular disease, 184 ischemic stroke (stroke), 425 abdominal aortic aneurysm] and 230 disease-free controls. We then conducted association studies with logistic regression, integrating the potential confounding effects of age, sex, diabetes, plasma lipids, and a history of previous hypertension, hypercholesterolemia, and smoking. RESULTS: Multivariate analyses with Lp(a) concentrations of >45 nmol/L (the 75th percentile value for controls) as the clinical cutoff showed increased Lp(a) concentrations to be a risk factor for all disease groups, with adjusted odds ratios ranging from 1.96 [95% confidence interval (CI) 1.24-3.08] for CAD to 2.33 (95% CI 1.39-3.89) for PVD. The risk conferred by Lp(a) appeared to be independent of other confounders, including exposure to statin/fibrate therapies. Similar odds ratios and CIs between disease groups indicated that increased Lp(a) conferred a similar risk for all groups studied. CONCLUSIONS: Lp(a) constitutes a stable risk factor of similar magnitude for 4 major forms of vascular disease. This association was not altered by exposure to standard lipid-lowering therapy.