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Nontraditional serum lipid variables and recurrent stroke risk.

ABSTRACT: Expert consensus guidelines recommend low-density lipoprotein cholesterol as the primary serum lipid target for recurrent stroke risk reduction. However, mounting evidence suggests that other lipid parameters might be additional therapeutic targets or at least also predict cardiovascular risk. Little is known about the effects of nontraditional lipid variables on recurrent stroke risk.We analyzed the Vitamin Intervention for Stroke Prevention study database comprising 3680 recent (<120 days) noncardioembolic stroke patients followed up for 2 years. Independent associations of baseline serum lipid variables with recurrent ischemic stroke (primary outcome) and the composite end point of ischemic stroke/coronary heart disease/vascular death (secondary outcomes) were assessed.Of all variables evaluated, only triglycerides/high-density lipoprotein cholesterol (HDL-C) ratio was consistently and independently related to both outcomes: compared with the lowest quintile, the highest triglycerides/HDL-C ratio quintile was associated with stroke (adjusted hazard ratio, 1.56; 95% confidence interval, 1.05-2.32) and stroke/coronary heart disease/vascular death (1.39; 1.05-1.83), including adjustment for lipid modifier use. Compared with the lowest quintile, the highest total cholesterol/HDL-C ratio quintile was associated with stroke/coronary heart disease/vascular death (1.45; 1.03-2.03). Low-density lipoprotein cholesterol/HDL-C ratio, non-HDL-C, elevated triglycerides alone, and low HDL-C alone were not independently linked to either outcome.Of various nontraditional lipid variables, elevated baseline triglycerides/HDL-C and total cholesterol/HDL-C ratios predict future vascular risk after a stroke, but only elevated triglycerides/HDL-C ratio is related to risk of recurrent stroke. Future studies should assess the role of triglycerides/HDL-C as a potential therapeutic target for global vascular risk reduction after stroke.

SUBMITTER: Park JH

PROVIDER: S-EPMC4213550 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Nontraditional serum lipid variables and recurrent stroke risk.

Park Jong-Ho JH Lee Juneyoung J Ovbiagele Bruce B

Stroke 20140918 11

<h4>Background and purpose</h4>Expert consensus guidelines recommend low-density lipoprotein cholesterol as the primary serum lipid target for recurrent stroke risk reduction. However, mounting evidence suggests that other lipid parameters might be additional therapeutic targets or at least also predict cardiovascular risk. Little is known about the effects of nontraditional lipid variables on recurrent stroke risk.<h4>Methods</h4>We analyzed the Vitamin Intervention for Stroke Prevention study ...[more]

PMID: 25236873

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Project description:Background and purposeLimited data exist on the performance of the revised Framingham Stroke Risk Score (R-FSRS) and the R-FSRS in conjunction with nontraditional risk markers. We compared the R-FSRS, original FSRS, and the Pooled Cohort Equation for stroke prediction and assessed the improvement in discrimination by nontraditional risk markers.MethodsSix thousand seven hundred twelve of 6814 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) were included. Cox proportional hazard, area under the curve, net reclassification improvement, and integrated discrimination increment analysis were used to assess and compare each stroke prediction risk score. Stroke was defined as fatal/nonfatal strokes (hemorrhagic or ischemic).ResultsAfter mean follow-up of 10.7 years, 231 of 6712 (3.4%) strokes were adjudicated (2.7% ischemic strokes). Mean stroke risks using the R-FSRS, original FSRS, and Pooled Cohort Equation were 4.7%, 5.9%, and 13.5%. The R-FSRS had the best calibration (Hosmer-Lemeshow goodness-of-fit, χ2=6.55; P=0.59). All risk scores were predictive of incident stroke. C statistics of R-FSRS (0.716) was similar to Pooled Cohort Equation (0.716), but significantly higher than the original FSRS (0.653; P=0.01 for comparison with R-FSRS). Adding nontraditional risk markers individually to the R-FSRS did not improve discrimination of the R-FSRS in the area under the curve analysis, but did improve category-less net reclassification improvement and integrated discrimination increment for incident stroke. The addition of coronary artery calcium to R-FSRS produced the highest category-less net reclassification improvement (0.36) and integrated discrimination increment (0.0027). Similar results were obtained when ischemic strokes were used as the outcome.ConclusionsThe R-FSRS downgraded stroke risk but had better calibration and discriminative ability for incident stroke compared with the original FSRS. Nontraditional risk markers modestly improved the discriminative ability of the R-FSRS, with coronary artery calcium performing the best.

Project description:Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS. Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders. Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12-1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48-0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (P I < 0.004-0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22-0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04-0.36) decreased the risk of IS (P I < 0.0001). Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.

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Nontraditional serum lipid variables and recurrent stroke risk.

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Nontraditional serum lipid variables and recurrent stroke risk.

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