Genetic variants of the promoter of the heme oxygenase-1 gene and their influence on cardiovascular disease (the Ludwigshafen Risk and Cardiovascular Health study).

BACKGROUND: Heme oxygenase-1 is an inducible cytoprotective enzyme which handles oxidative stress by generating anti-oxidant bilirubin and vasodilating carbon monoxide. A (GT)n dinucleotide repeat and a -413A>T single nucleotide polymorphism have been reported in the promoter region of HMOX1 to both influence the occurrence of coronary artery disease and myocardial infarction. We sought to validate these observations in persons scheduled for coronary angiography. METHODS: We included 3219 subjects in the current analysis, 2526 with CAD including a subgroup of CAD and MI (n = 1339) and 693 controls. Coronary status was determined by coronary angiography. Risk factors and biochemical parameters (bilirubin, iron, LDL-C, HDL-C, and triglycerides) were determined by standard procedures. The dinucleotide repeat was analysed by PCR and subsequent sizing by capillary electrophoresis, the -413A>T polymorphism by PCR and RFLP. RESULTS: In the LURIC study the allele frequency for the -413A>T polymorphism is A = 0,589 and T = 0,411. The (GT)n repeats spread between 14 and 39 repeats with 22 (19.9%) and 29 (47.1%) as the two most common alleles. We found neither an association of the genotypes or allelic frequencies with any of the biochemical parameters nor with CAD or previous MI. CONCLUSION: Although an association of these polymorphisms with the appearance of CAD and MI have been published before, our results strongly argue against a relevant role of the (GT)n repeat or the -413A>T SNP in the HMOX1 promoter in CAD or MI.

Low serum zinc concentrations predict mortality in patients referred to coronary angiography.

Zinc deficiency is common among the elderly and has been associated with oxidative stress, immune dysfunction and CVD. We examined whether low zinc concentrations are associated with total, cardiovascular and non-cardiovascular mortality. Serum zinc concentrations were measured in 3316 patients from the Ludwigshafen Risk and Cardiovascular Health study, who were routinely referred to coronary angiography at a single tertiary care centre in Southwest Germany. After a median follow-up period of 7.75 years, 769 patients had died, including 484 deaths due to cardiovascular and 261 due to non-cardiovascular causes. After adjustments for cardiovascular risk factors and other possible confounders, the hazard ratios in the first when compared with the fourth zinc quartile, and per quartile decrease were 1.44 (95 % CI 1.13, 1.83; P = 0.001) and 1.15 (95 % CI 1.07, 1.24; P < 0.001) for total mortality, 2.20 (95 % CI 1.42, 3.42; P < 0.001) and 1.32 (95 % CI 1.16, 1.50; P < 0.001) for non-cardiovascular mortality and 1.24 (95 % CI 0.92, 1.66; P = 0.162) and 1.10 (95 % CI 1.01, 1.21; P = 0.038) for cardiovascular mortality. Furthermore, serum zinc concentrations correlated negatively with age and markers of inflammation and positively with antioxidants. The present results suggest that zinc deficiency may contribute to a reduced life expectancy in patients scheduled for coronary angiography.

Low vitamin d levels predict stroke in patients referred to coronary angiography.

BACKGROUND AND PURPOSE: Vitamin D deficiency is common among the elderly and may contribute to cerebrovascular diseases. We aimed to elucidate whether low vitamin D levels are predictive for fatal stroke. METHODS: The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study includes 3316 patients who were referred to coronary angiography at baseline between 1997 and 2000. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured in 3299 and 3315 study participants, respectively. To account for the seasonal variation of vitamin D metabolites, we calculated z values for the 25(OH)D and 1,25(OH)2D concentrations within each month of blood draw. RESULTS: During a median follow-up time of 7.75 years, 769 patients died, including 42 fatal (ischemic and hemorrhagic) strokes. When compared with survivors in binary logistic-regression analyses, the odds ratios (with 95% CIs) for fatal stroke were 0.58 (0.43 to 0.78; P<0.001) per z value of 25(OH)D and 0.62 (0.47 to 0.81; P<0.001) per z value of 1,25(OH)2D. After adjustment for several possible confounders, these odds ratios remained significant for 25(OH)D at 0.67 (0.46 to 0.97; P=0.032) and for 1,25(OH)2D at 0.72 (0.52 to 0.99; P=0.047). Z values of 25(OH)D and 1,25(OH)2D were also reduced in the 274 patients who had a history of previous cerebrovascular disease events at baseline. CONCLUSIONS: Low levels of 25(OH)D and 1,25(OH)2D are independently predictive for fatal strokes, suggesting that vitamin D supplementation is a promising approach in the prevention of strokes.

Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography.

CONTEXT: Vitamin D has been shown to influence cardiac contractility and myocardial calcium homeostasis. OBJECTIVES: We aimed to elucidate whether insufficient vitamin D status is associated with heart failure and sudden cardiac death (SCD). DESIGN, SETTING, AND PARTICIPANTS: We measured 25-hydroxyvitamin D [25(OH)D] levels in 3299 Caucasian patients who were routinely referred to coronary angiography at baseline (1997-2000). MAIN OUTCOME MEASURES: The main outcome was cross-sectional associations of 25(OH)D levels with measures of heart failure and Cox proportional hazard ratios for deaths due to heart failure and for SCD according to vitamin D status. RESULTS: 25(OH)D was negatively correlated with N-terminal pro-B-type natriuretic peptide and was inversely associated with higher New York Heart Association classes and impaired left ventricular function. During a median follow-up time of 7.7 yr, 116 patients died due to heart failure and 188 due to SCD. After adjustment for cardiovascular risk factors, the hazard ratios (with 95% confidence intervals) for death due to heart failure and for SCD were 2.84 (1.20-6.74) and 5.05 (2.13-11.97), respectively, when comparing patients with severe vitamin D deficiency [25(OH)D <25 nmol/liter)] with persons in the optimal range [25(OH)D > or =75 nmol/liter]. In all statistical analyses, we obtained similar results with 25(OH)D and with 1,25-dihydroxyvitamin D. CONCLUSIONS: Low levels of 25(OH)D and 1,25-dihydroxyvitamin D are associated with prevalent myocardial dysfunction, deaths due to heart failure, and SCD. Interventional trials are warranted to elucidate whether vitamin D supplementation is useful for treatment and/or prevention of myocardial diseases.

Low serum levels of 25-hydroxyvitamin D predict fatal cancer in patients referred to coronary angiography.

Accumulating evidence suggests that vitamin D may protect against cancer, but results from epidemiologic studies are inconclusive so far, and other studies looking into the prospective association of total cancer mortality and serum 25-hydroxyvitamin D [25(OH)D] levels, which are considered to be the best indicator of vitamin D status, are scarce. We measured 25(OH)D and 1,25-dihydroxyvitamin D in 3,299 patients from the Ludwigshafen Risk and Cardiovascular Health study. The baseline examination was done between July 1997 and January 2000 and included a fasting blood sampling in the morning before coronary angiography. During a median follow-up period of 7.75 years, 95 patients died due to cancer. After adjustment for possible confounders, the Cox proportional hazard ratio (95% confidence interval) of the fourth 25(OH)D quartile was 0.45 (0.22-0.93) when compared with the first quartile and the hazard ratio per increase of 25 nmol/L in serum 25(OH)D concentrations was 0.66 (0.49-0.89). We found no association between serum 1,25-dihydroxyvitamin D levels and fatal cancer. In summary, our data suggest that low levels of 25(OH)D are associated with increased risk of fatal cancer in patients referred to coronary angiography and that the maintenance of a sufficient vitamin D status might therefore be a promising approach for the prevention and/or treatment of cancer.

Alanine to serine polymorphism at position 986 of the calcium-sensing receptor associated with coronary heart disease, myocardial infarction, all-cause, and cardiovascular mortality.

BACKGROUND: Disorders of calcium homeostasis have been implicated in atherosclerosis. The calcium-sensing receptor (CASR) is crucial to the regulation of calcium metabolism. An alanine (A) to serine (S) polymorphism at codon 986 (A986S) of the CASR gene has been associated with higher calcium and osteoporosis; the association with coronary artery disease (CAD) has not been studied. METHODS AND RESULTS: We investigated this polymorphism in individuals with CAD (n = 2561), including survivors of myocardial infarction (MI) (n = 1358) compared to 698 controls without angiographic CAD. Compared to AA homozygotes, the prevalence of CAD [multivariate odds ratio 1.25; 95% confidence interval (CI) 1.02-1.54] and previous MI (multivariate odds ratio 1.33; 95% CI 1.06-1.68) was increased in carriers of at least one S-allele. With each S-allele, the prevalence of CAD and MI increased 1.22-fold (95% CI 1.02-1.47) and 1.30-fold (95% CI 1.06-1.60), respectively. Fully adjusted hazard ratios for total and cardiovascular mortality per one S-allele were 1.24 (95% CI 1.05-1.46) and 1.38 (95% CI 1.13-1.67), respectively. In carriers of at least one S-allele, the adjusted hazard ratios for all-cause and cardiovascular death were 1.25 (95% CI 1.04-1.51) and 1.48 (95% CI 1.18-1.86), respectively. These associations were independent of cardiovascular risk factors, calcium and phosphate. The S-allele was associated with higher calcium (P < 0.001) and PTH (P < 0.02), and lower phosphate (P < 0.003) in CAD patients and controls. CONCLUSION: Serine at position 986 of CASR may be an independent genetic predictor of angiographic CAD, previous MI, and cardiovascular mortality.

Adiponectin and mortality in patients undergoing coronary angiography.

CONTEXT: The adipokine adiponectin has been suggested to protect against coronary artery disease (CAD). However, studies addressing the association between adiponectin and mortality are sparse. OBJECTIVE: The objective of the study was to elucidate the relationship between adiponectin and mortality. DESIGN, SETTING, AND PARTICIPANTS: Adiponectin was determined in 2473 persons with and 673 persons without angiographic CAD. During a mean follow-up period of 5.45 yr, 427 persons with CAD and 55 persons without CAD died. MAIN OUTCOME MEASURE: Hazard ratios for mortality according to adiponectin levels were measured. RESULTS: Adiponectin was positively related to female gender, age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, and N-terminal pro-B-type natriuretic peptide. It was inversely related to glomerular filtration rate, body mass index, and triglycerides and was low in diabetes mellitus and CAD. An increase of 1 sd in adiponectin was associated with unadjusted and fully adjusted hazard ratios for death from any cause of 1.31 [95% confidence interval (CI) 1.20-1.42] and 1.22 (95% CI 1.12-1.34), and for death from cardiovascular causes of 1.32 (95% CI 1.19-1.45) and 1.23 (95% CI 1.11-1.37), respectively. In angiographic CAD, stable CAD, and unstable CAD, the predictive value of adiponectin was similar to that in the entire cohort, but it did not attain statistical significance in persons without angiographic CAD. Adiponectin was also positively related to the risk of death from noncardiovascular causes. CONCLUSIONS: Despite the common view about adiponectin as a protective molecule in cardiovascular disease, high adiponectin independently predicts all-cause, cardiovascular, and noncardiovascular mortality in individuals with CAD.

Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease.

CONTEXT: Free fatty acids (FFAs) are associated with several cardiovascular risk factors and exert harmful effects on the myocardium. OBJECTIVE: The aim of our study was to elucidate the relationship between FFAs and mortality in subjects who underwent coronary angiography. DESIGN, SETTING, AND PARTICIPANTS: Ludwigshafen Risk and Cardiovascular Health is a prospective cohort study of Caucasians who had undergone coronary angiography at baseline (1997-2000). During a median time of follow-up of 5.38 yr, 513 deaths had occurred among 3315 study participants with measured FFAs. MAIN OUTCOME MEASURE: Hazard ratios for mortality according to FFA levels were measured. RESULTS: At the fourth quartile of FFAs, fully adjusted hazard ratios for death from any cause and cardiovascular causes were 1.58 (P = 0.002) and 1.83 (P = 0.001), respectively. In persons with angiographic coronary artery disease (CAD), stable CAD, and unstable CAD, the predictive value of FFAs was similar to that in the entire cohort, but the association did not attain statistical significance in persons without CAD analyzed separately. FFA levels were not related to the presence of angiographic CAD but were elevated in subjects with unstable CAD, compared with probands with stable CAD. Furthermore, FFAs increased with the severity of heart failure and were positively correlated with N-terminal pro-B-type natriuretic peptide (P < 0.001). CONCLUSIONS: FFA levels independently predict all-cause and cardiovascular mortality in subjects with angiographic CAD. A possible diagnostic use of FFAs warrants further studies, but our results may underline the importance of therapeutic approaches to influence FFA metabolism.

Serum gamma-glutamyl transferase and mortality in persons undergoing coronary angiography-The Ludwigshafen Risk and Cardiovascular Health Study.

OBJECTIVE: Serum gamma-glutamyl transferase (GGT) seems to be a predictor for coronary artery disease (CAD). The objective of this study was to elucidate the relationship between GGT and total as well as cardiovascular mortality. METHODS: Serum levels of GGT were determined in 2556 subjects with and 699 subjects without angiographic evidence of CAD in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. RESULTS: Serum GGT was positively associated with male gender, alcohol consumption and markers of the metabolic syndrome (triglycerides, blood pressure, waist circumference and insulin resistance). It was positively related to aspartate aminotransferase, alanine aminotransferase, C-reactive protein, interleukin-6, and negatively related to glutathione and increased age. During a mean follow-up period of 7.75 years, 754 subjects died. Compared with subjects in the lowest quartile of GGT, the unadjusted hazard ratios (95% CI) for all-cause death were 1.2 (0.9-1.5), 1.4 (1.1-1.8) and 1.9 (1.5-2.3), respectively, in other GGT quartiles. Hazard ratios (CI) for death from cardiovascular causes were 1.4 (1.0-2.0), 1.8 (1.4-2.5) and 2.2 (1.6-2.9). After adjustment for age, gender and cardiovascular risk factors GGT remained a significant predictor for total and cardiovascular mortality. In angiographic CAD the predictive value of GGT was also significant and similar to that in the entire cohort. CONCLUSION: Serum GGT is predictive of all-cause and cardiovascular mortality in individuals with CAD independently of other cardiovascular risk factors.

Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality.

BACKGROUND: In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality. METHODS: Prospective cohort study of 3258 consecutive male and female patients (mean [SD] age, 62 [10] years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths. RESULTS: During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for all-cause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29-2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels). CONCLUSIONS: Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.

Lymphocytes of type 2 diabetic women carry a high load of stable chromosomal aberrations: a novel risk factor for disease-related early death.

OBJECTIVE: Diabetes is associated with an increased risk of death in women. Oxidative stress due to chronic hyperglycemia leads to the generation of reactive oxygen species and loss of chromosomal integrity. To clarify whether diabetes is a premature aging syndrome, we determined telomere erosion dynamics and occurrence of structural chromosomal aberrations in women of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. RESEARCH DESIGN AND METHODS: Telomere lengths and karyotypes were examined in peripheral blood mononuclear cells. Regarding these parameters, surviving and deceased type 2 diabetic women of the LURIC study were compared with nondiabetic LURIC women with or without coronary heart disease and with healthy female control subjects. RESULTS: Significantly enhanced telomere attrition was seen in all LURIC subjects compared with healthy control subjects. Although the average telomere-length loss is equivalent to well >10 years of healthy aging, telomere erosion was not associated with outcome within the LURIC cohort. However, strikingly high numbers of stable chromosomal aberrations were found in type 2 diabetic women but not in LURIC disease control subjects or in healthy individuals. Furthermore, within the younger age- groups, deceased type 2 diabetes patients had significantly more marker chromosomes than the surviving type 2 diabetic patients. CONCLUSIONS: All women at high risk for cardiovascular death have accelerated telomere erosion, not caused by type 2 diabetes per se but likely linked to other risk factors, including dyslipidemia. By contrast, the occurrence of marker chromosomes is associated with type 2 diabetes and is a novel risk factor for type 2 diabetes-related early death.

Implications of resistin plasma levels in subjects undergoing coronary angiography.

BACKGROUND: The adipokine resistin, which is thought to serve as a link between obesity and insulin resistance, was recently shown to exert proatherosclerotic features. OBJECTIVE: Our study aimed to explore the involvement of resistin in cardiovascular disease by investigating the associations of resistin with angiographic coronary artery disease (CAD), cardiovascular risk factors and mortality. DESIGN: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a prospective study of white subjects who had undergone coronary angiography. PATIENTS AND MEASUREMENTS: Resistin levels were determined in 1162 subjects with (n = 911) and without (n = 251) angiographic CAD. During a mean follow-up period of 5.47 years, 198 deaths occurred among our probands. RESULTS: Resistin was positively correlated with C-reactive protein (CRP; r = 0.245, P < 0.001), vascular adhesion molecule-1 (VCAM-1; r = 0.327, P < 0.001) and intercellular adhesion molecule-1 (ICAM-1; r = 0.197, P < 0.001) and was negatively correlated with glomerular filtration rate (GFR; r = -0.438, P < 0.001) and high density lipoprotein (HDL; r = -0.196, P < 0.001). Multiple regression analysis revealed that GFR was the strongest predictive variable for resistin. Angiographic CAD, type 2 diabetes, smoking, hypertension and body mass index (BMI) were not associated with resistin. Compared to the first quartile, we observed an increased risk for cardiovascular and noncardiovascular mortality at the fourth quartile of resistin, but only the association between resistin and noncardiovascular mortality remained significant after multivariable adjustments [hazard ratio (HR) 4.92, 95% confidence interval (CI) 1.66-14.6, P = 0.004]. CONCLUSIONS: Resistin plasma concentrations are related to inflammatory processes and renal function but our study does not support the hypothesis of resistin as an independent cardiovascular risk factor. The unexpected association of resistin with noncardiovascular mortality still warrants further study.

Asymmetrical dimethylarginine independently predicts total and cardiovascular mortality in individuals with angiographic coronary artery disease (the Ludwigshafen Risk and Cardiovascular Health study).

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is increased in conditions associated with increased risk of atherosclerosis. We investigated the use of ADMA to predict total and cardiovascular mortality in patients scheduled for coronary angiography. METHODS: In 2543 persons with and 695 without coronary artery disease (CAD) identified by angiography we measured ADMA and recorded total and cardiovascular mortality during a median follow-up of 5.45 years. RESULTS: ADMA was correlated positively to age, female sex, diabetes mellitus, former and current smoking, and C-reactive protein and inversely to HDL cholesterol and triglycerides. ADMA was not associated with body mass index, hypertension, LDL cholesterol, or the presence or absence of angiographic CAD. Glomerular filtration rate and homocysteine were the strongest predictors of ADMA. At the 2nd, 3rd and 4th quartile of ADMA, hazard ratios for all-cause mortality adjusted for age, sex, and cardiovascular risk factors were 1.12 [95% confidence interval (CI) 0.83-1.52], 1.35 (95% CI 1.01-1.81), and 1.87 (95% CI 1.43-2.44), respectively, compared with the 1st quartile. Hazard ratios for cardiovascular death were 1.13 (95% CI 0.78-1.63), 1.42 (95% CI 1.00-2.02), and 1.81 (95% CI 1.31-2.51). ADMA in the highest quartile remained predictive of mortality after accounting for medication at baseline. The predictive value of ADMA was similar to that in the entire cohort in persons with CAD, stable or unstable, but was not statistically significant in persons without angiographic CAD. CONCLUSIONS: ADMA concentration predicts all-cause and cardiovascular mortality in individuals with CAD independently of established and emerging cardiovascular risk factors.

N-terminal pro-B-type natriuretic peptide predicts total and cardiovascular mortality in individuals with or without stable coronary artery disease: the Ludwigshafen Risk and Cardiovascular Health Study.

BACKGROUND: Measurement of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) measurement can be used to predict mortality in patients with acute coronary syndromes. Information on the value of NT-pro-BNP in clinically stable persons scheduled for angiography is limited. METHODS: We used Cox proportional hazards regression to examine the effect of NT-pro-BNP on total and cardiovascular mortality in 1135 with and 506 individuals without stable coronary artery disease (CAD). RESULTS: NT-pro-BNP was associated with New York Heart Association functional class, left ventricular (LV) systolic function, and LV end-diastolic pressure. NT-pro-BNP was positively related to age, female sex, hypertension, and former and current smoking and negatively related to body mass index and glomerular filtration rate. During a median follow-up of 5.45 years, NT-pro-BNP concentrations of 100-399, 400-1999, or > or =2000 ng/L resulted in unadjusted hazard ratios (95% CI) for all-cause death of 3.2 (1.8-5.6), 6.63 (3.8-11.6), and 16.5 (9.2-29.8), respectively, compared with concentrations <100 ng/L. Hazard ratios (CI) for death from cardiovascular causes were 3.8 (1.8-8.2), 9. 3 (4.4-19.5), and 22.2 (10.2-48.4). NT-pro-BNP remained predictive of total and cardiovascular mortality after accounting for age, sex, diabetes mellitus, body mass index, smoking, hypertension, dyslipidemia, glomerular filtration rate, presence or absence of CAD on angiography, cardiovascular medication, revascularization at baseline, clinical signs of heart failure, LV systolic function, and C-reactive protein. CONCLUSIONS: NT-pro-BNP is predictive of all-cause and cardiovascular mortality in individuals with or without stable angiographic CAD independently of other cardiovascular risk factors, coronary atherosclerosis, and cardiac function.

Elevated plasma free fatty acids predict sudden cardiac death: a 6.85-year follow-up of 3315 patients after coronary angiography.

AIMS: Sudden cardiac death (SCD) is the most common fatal cardiovascular event. Free fatty acids (FFAs) exert several harmful effects on the myocardium and may therefore contribute to SCD. We examined whether fasting FFA predict SCD in patients who had undergone coronary angiography. METHODS AND RESULTS: FFAs were measured at baseline (1997-2000) in 3315 patients scheduled for coronary angiography. Angiographic coronary artery disease was found in 2231 study participants. After a median time of follow-up of 6.85 years, 165 SCD occurred in the entire study population. In a Cox proportional hazards model, the unadjusted hazard ratio (HR) for SCD in the fourth when compared with the first FFA quartile was 2.95 (95% CI 1.84-4.73; P < 0.001). After adjustment for common and emerging cardiovascular risk factors, the HR remained significant at 1.76 (1.03-3.00; P = 0.038). High FFA levels were also significantly associated with all-cause and cardiovascular mortality, even after exclusion of patients with SCD. CONCLUSION: Our study shows that elevated plasma FFAs are an independent risk factor for future SCD in patients referred to coronary angiography. These results may suggest that modulation of myocardial fatty acid uptake and/or metabolism are a possible target of treatment, but it still remains to be clarified whether high FFA levels are a cause or a consequence of pathological processes that underlie the association between FFA and SCD.

Lipoprotein-associated phospholipase A2 predicts 5-year cardiac mortality independently of established risk factors and adds prognostic information in patients with low and medium high-sensitivity C-reactive protein (the Ludwigshafen risk and cardiovascular health study).

BACKGROUND: Lipoprotein-associated phospholipase A(2) (LpPLA(2)), also denoted as platelet-activating factor acetylhydrolase, is a lipoprotein-bound enzyme involved in inflammation and atherosclerosis. In this cohort study we investigated LpPLA(2) activity to predict cardiac mortality in patients scheduled for coronary angiography. METHODS: LpPLA(2) activity was determined in 2513 patients with and in 719 patients without angiographically confirmed coronary artery disease (CAD). RESULTS: During the median observation period of 5.5 years, 501 patients died. In patients with tertiles of LpPLA(2) activity of 420-509 U/L or >or=510 U/L, unadjusted hazard ratios (HRs) for cardiac death were 1.7 (95% CI 1.3-2.4; P = 0.001), and 1.9 (95% CI 1.4-2.5; P <0.001), respectively, compared with patients with LpPLA(2) activity