| 1. |
- Musunuru, Kiran, et al.
(author)
-
Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk.
- 2009
-
In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 29, s. 628-1975
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies. METHODS AND RESULTS: We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4594 initially healthy men and women (the Malmö Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified 3 major independent (ie, zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described "atherogenic lipoprotein phenotype." Several genes that may underlie this phenotype-CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL-are suggested by SNPs associated with the combination of small/medium LDL and large HDL. CONCLUSIONS: PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD.
|
|
| 2. |
|
|
| 3. |
- Engström, Gunnar, et al.
(author)
-
Carotid Intima-Media Thickness, Systemic Inflammation, and Incidence of Heart Failure Hospitalizations.
- 2009
-
In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 29, s. 1691-1695
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: This study explored the relationships between carotid intima-media thickness (IMT), plasma levels of C-reactive protein (CRP), and incidence of heart failure hospitalizations. METHODS AND RESULTS: Men and women from the general population (n=4691), without history of myocardial infarction or stroke, were examined. Incidence of hospitalizations attributable to heart failure was studied over a mean follow-up of 13 years. A total of 75 subjects were hospitalized with a primary diagnosis of heart failure. Adjusted for risk factors, the hazards ratios (95% CI) were 1.00, 0.98 (0.36 to 2.7), 1.9 (0.80 to 4.6), and 2.7 (1.1 to 6.2), respectively, for the 1st, 2nd, 3rd, and 4th quartiles of IMT (P for trend=0.003). The HR associated with CRP levels >/=3 mg/L (versus <1 mg/L) was 2.0 (95% CI: 1.06 to 3.9) after adjustments for risk factors. There was a significant interaction between IMT and CRP on heart failure incidence (P=0.028). Subjects with CRP >/=3 mg/L and IMT in the 4th quartile had an adjusted HR of 3.7 (1.9 to 7.1) compared to those with CRP <3 mg/L and IMT in quartile 1 to 3. CONCLUSIONS: High IMT and high CRP are both independent risk factors for incidence of heart failure requiring hospitalization. The joint exposure to both risk factors substantially increases the risk.
|
|
| 4. |
- Engström, Gunnar, et al.
(author)
-
Leukocyte Count and Incidence of Hospitalizations Due to Heart Failure
- 2009
-
In: Circulation Heart Failure. - 1941-3297. ; 2:3, s. 217-222
-
Journal article (peer-reviewed)abstract
- Background-Leukocyte concentration in blood is a classical marker of systemic inflammation. Whether high leukocyte counts are associated with incidence of heart failure (HF) is unknown. This population-based study explored whether the leukocyte concentrations were associated with incidence of hospitalizations due to HF. Methods and results-Leukocyte counts were measured in 16 940 men from the general population (mean age 44 years) without history of myocardial infarction or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 23 years of follow-up, in relation to quartiles of leukocytes. Subjects with myocardial infarction during follow-up were censored in the main analysis. During the follow-up, 436 men were hospitalized due to HF. Incidence of HF hospitalizations was increased in men with high leukocyte counts. After adjustments for confounding factors, the adjusted hazards ratio (HR, 95% CI) for HF hospitalization was 1.00 (reference), 1.26 (0.93 to 1.7), 1.24 (0.91 to 1.7), and 1.73 (1.3 to 2.3), respectively, for men with leukocytes in the 1st, 2nd, 3rd, and 4th (highest) quartiles (trend, P<0.001). This relationship was consistent in smokers and nonsmokers and in men with and without hypertension, respectively. Conclusion-High leukocyte counts in middle-aged men were associated with increased long-term incidence of HF hospitalizations. (Circ Heart Fail. 2009;2:217-222.)
|
|
| 5. |
- Fava, Cristiano, et al.
(author)
-
The V433M Variant of the CYP4F2 Is Associated With Ischemic Stroke in Male Swedes Beyond Its Effect on Blood Pressure.
- 2008
-
In: Hypertension. - 1524-4563. ; 52, s. 373-380
-
Journal article (peer-reviewed)abstract
- Cytochrome (CYP) 4A11 and CYP4F2 are responsible for renal production of 20-hydroxyeicosatetraenoic acid, a vasoconstrictor and natriuretic substance. The CYP4A11 F434S and CYP4F2 V433M polymorphisms reduce 20-hydroxyeicosatetraenoic acid production in vitro. The aim of the present study was to evaluate the effect of these polymorphisms on blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. The polymorphisms were genotyped in the cardiovascular cohort of the Malmö Diet and Cancer Study. The incidence of cardiovascular events (coronary events, n=276; ischemic stroke, n=199) was monitored over 10 years of follow-up. The analysis of BP levels was performed twice: either excluding or including subjects under antihypertensive treatment. In the whole population, CYP4A11 S434S homozygotes had higher systolic BP, both crude and adjusted for the number of antihypertensive drugs, and higher prevalence of hypertension with respect to F434 carriers. Male, but not female, CYP4F2 M433 carriers had significantly higher crude and adjusted systolic and diastolic BPs and a trend toward higher hypertension prevalence (P=0.06) with respect to V433V homozygotes. After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male CYP4F2 M433 carriers was significantly higher with respect to V433V homozygotes (hazard ratio: 1.69; 95% CI: 1.10 to 2.60) even when baseline BP levels and hypertension prevalence were included in the Cox proportional hazard model. A common CYP4F2 V433M polymorphism might increase the risk of incident ischemic stroke in male subjects only partially through its elevating effect on BP. Additional studies are needed to confirm these data.
|
|
| 6. |
- Melander, Olle, et al.
(author)
-
Novel and conventional biomarkers for prediction of incident cardiovascular events in the community.
- 2009
-
In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 302:1, s. 49-57
-
Journal article (peer-reviewed)abstract
- CONTEXT: Prior studies have demonstrated conflicting results regarding how much information novel biomarkers add to cardiovascular risk assessment. OBJECTIVE: To evaluate the utility of contemporary biomarkers for predicting cardiovascular risk when added to conventional risk factors. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 5067 participants (mean age, 58 years; 60% women) without cardiovascular disease from Malmö, Sweden, who attended a baseline examination between 1991 and 1994. Participants underwent measurement of C-reactive protein (CRP), cystatin C, lipoprotein-associated phospholipase 2, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide (N-BNP) and underwent follow-up until 2006 using the Swedish national hospital discharge and cause-of-death registers and the Stroke in Malmö register for first cardiovascular events (myocardial infarction, stroke, coronary death). MAIN OUTCOME MEASURES: Incident cardiovascular and coronary events. RESULTS: During median follow-up of 12.8 years, there were 418 cardiovascular and 230 coronary events. Models with conventional risk factors had C statistics of 0.758 (95% confidence interval [CI], 0.734 to 0.781) and 0.760 (0.730 to 0.789) for cardiovascular and coronary events, respectively. Biomarkers retained in backward-elimination models were CRP and N-BNP for cardiovascular events and MR-proADM and N-BNP for coronary events, which increased the C statistic by 0.007 (P = .04) and 0.009 (P = .08), respectively. The proportion of participants reclassified was modest (8% for cardiovascular risk, 5% for coronary risk). Net reclassification improvement was nonsignificant for cardiovascular events (0.0%; 95% CI, -4.3% to 4.3%) and coronary events (4.7%; 95% CI, -0.76% to 10.1%). Greater improvements were observed in analyses restricted to intermediate-risk individuals (cardiovascular events: 7.4%; 95% CI, 0.7% to 14.1%; P = .03; coronary events: 14.6%; 95% CI, 5.0% to 24.2%; P = .003). However, correct reclassification was almost entirely confined to down-classification of individuals without events rather than up-classification of those with events. CONCLUSIONS: Selected biomarkers may be used to predict future cardiovascular events, but the gains over conventional risk factors are minimal. Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.
|
|
| 7. |
- Montagnana, Martina, et al.
(author)
-
The Pro12Ala polymorphism of the PPARG gene is not associated with the metabolic syndrome in an urban population of middle-aged Swedish individuals.
- 2008
-
In: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; 25:8, s. 902-908
-
Journal article (peer-reviewed)abstract
- BACKGROUND: To determine if the common Pro12Ala polymorphism (rs1801282) of the peroxisome proliferator-activated receptor (PPARG) gene is associated with the metabolic syndrome (MetS) or with its individual components in middle-aged Swedish individuals. METHODS: MetS was defined according to the National Cholesterol Education Program/Adult Panel III (NCEP/ATP III), the International Diabetes Federation (IDF) and the European Group for the Study of Insulin Resistance (EGIR) criteria in a population-based sample of nearly 5000 subjects participating in the Malmö Diet and Cancer-cardiovascular arm. RESULTS: Of the subjects included in the analysis, 21.8, 29.4 and 20.4% had MetS according to the NCEP/ATP III, IDF and EGIR (only in subjects without diabetes) definitions, respectively. The Pro12Ala was not associated with MetS or with its individual components. These results were similar when patients with diabetes were excluded. Hypertensive and obese ala-carriers had lower fasting glucose and hypertensive ala-carriers also had lower level triglycerides (P < 0.05). CONCLUSIONS: Our data do not support a major role for the Pro12Ala variant of the PPARG gene in MetS and its individual components. The modest difference in triglyceride and glucose levels, restricted to hypertensive and obese subjects in our cohort, suggests that the polymorphism has a minor effect on glucose and lipid metabolism, particularly in individuals at risk for gluco-metabolic disturbances.
|
|
| 8. |
- Smith, Gustav, et al.
(author)
-
Common Genetic Variants on Chromosome 9p21 Confers Risk of Ischemic Stroke A Large-Scale Genetic Association Study
- 2009
-
In: Circulation: Cardiovascular Genetics. - 1942-325X. ; 2:2, s. 159-164
-
Journal article (peer-reviewed)abstract
- Background-Epidemiological studies indicate a genetic contribution to ischemic stroke risk, but specific genetic variants remain unknown, with the exception of a few rare variants. Recent genome-wide association studies identified and replicated common genetic variants on chromosome 9p21 to confer risk of coronary heart disease. We examined whether these variants are associated with ischemic stroke. Methods and Results-We genotyped 6 common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in 2 population-based studies in southern Sweden, the Lund Stroke Register (n = 1837 cases, 947 controls) and the Malmo Diet and Cancer study (MDC; n = 888 cases, 893 controls). We examined association in each study and in the pooled dataset. Adjustments were made for cardiovascular risk factors and further for previous myocardial infarction in MDC. We found a modest increase in ischemic stroke risk for 2 common (minor allele frequencies 0.46 to 0.49) variants, rs2383207 (P = 0.04 in Lund Stroke Register, P = 0.01 in MDC) and rs10757274 (P = 0.03 in Lund Stroke Register, P = 0.03 in MDC), in each sample independently. The strength of the association increased when samples were pooled with an odds ratio of 1.15 (95% CI, 1.05 to 1.25; P = 0.002) for the strongest variant rs2383207. Results were similar after adjustment for clinical covariates. rs1333049 also showed significant association in MDC, which increased in the pooled sample (P = 0.004). Conclusions-In this large sample (n = 4565), we detected common genetic determinants for ischemic stroke on chromosome 9p21. Our findings indicate that ischemic stroke shares pathophysiological determinants with coronary heart disease and other arterial diseases and highlight the need for large sample sizes in stroke genetics. (Circ Cardiovasc Genet. 2009; 2: 159-164.)
|
|
