Leptin is associated with increased risk of myocardial infarction

Abstract

Abstract. So Èderberg S, Ahre Ân B, Jansson J-H, Johnson O, Hallmans G, Asplund K, Olsson T (Umea Ê University, Umea Ê; and Lund University, Malmo È, Sweden). Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999; 246: 409± 418.Objectives and design. Leptin is involved in the regulation of bodyweight and metabolism in man and might also be involved in the pathophysiology of the insulin resistance syndrome, which is associated with the development of cardiovascular diseases. We tested whether leptin is a risk factor for acute myocardial infarction (AMI) in a nested casereferent study. Subjects and methods. Sixty-two men with first-ever AMI were identified who, prior to AMI, had participated in population-based health surveys in Northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographical region. Blood pressure, body mass index (BMI) and the presence of smoking, diabetes and hypertension were recorded. Total cholesterol, apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B), plasminogen activator inhibitor (PAI-1), insulin, and leptin were analysed in stored samples. Their influences on first-ever AMI were analysed by conditional logistic regression analysis. Results. Men with first-ever AMI had higher BMI, plasma insulin and leptin, and diastolic blood pressure than the referents. Furthermore, they had lower plasma apo A-1 and were more often smokers. Smoking, high leptin, PAI-1 and cholesterol, and low apo A-1 levels were significant risk factors for first-ever AMI in univariate analysis. High leptin (OR 8.97; 95% CI: 1.73±46.5) and cholesterol (OR 5.18; 95% CI: 1.34±20.0) levels remained significant risk factors for AMI in a multivariate model. High apo A-1 was protective (OR = 0.13; 95% CI: 0.03±0.55). The combination of high leptin and low apo A-1 was associated with a particularly pronounced increased risk for AMI. Conclusion. Plasma leptin strongly predicts firstever AMI. Our data support the hypothesis that leptin is an important link in the development of cardiovascular disease in obesity.

Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

“…A pooled meta‐analysis shows the highest quantile (ie, tertile, quartile, or quintile) of blood PAI‐1 levels is associated with higher risk of CHD incidence compared with the lowest quantile (OR=2.17; 95% CI: 1.53, 3.07; Figure 2A) in an age‐and sex‐adjusted model 11, 12, 13, 14, 15, 16, 17, 18, 19, 22. The overall heterogeneity across studies is high (I 2 =71.5%, P <0.001; Figure 2A).…”

“…The overall heterogeneity across studies is high (I 2 =71.5%, P <0.001; Figure 2A). The association estimate is reduced but remains significant in studies using a multivariable‐adjusted model (OR=1.46; 95% CI: 1.13, 1.88; Figure 2B),11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 31 with a lower overall heterogeneity compared with studies applying only an age‐and sex‐adjusted model (I 2 =55.7%, P =0.008; Figure 2B). In the subgroup meta‐analysis based on different PAI‐1 quantile scales, heterogeneity is observed most strongly in the quartile subgroup in both age‐ and sex‐adjusted model (I 2 =81.6%, P <0.001; Figure 2A) and the multivariable‐adjusted model (I 2 =61.7%, P <0.016; Figure 2B).…”

“…The association of elevated plasma PAI‐1 levels with CHD incidence has been reported in longitudinal studies 11, 12, 13, 14, 15, 16, 17, 18, 19. However, this association did not always remain consistent after adjusting for cardiovascular risk factors 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23. On the one hand, these inconsistencies could be due to small sample sizes and/or restricted study populations (eg, type 2 diabetes mellitus patients, obese individuals, or HIV patients) 20, 24.…”

“…Ten studies that adjusted only for age and sex reported association between PAI‐1 and CHD incidence (Table S1), while 13 studies found the same association following adjustment for multiple covariates (eg, BMI, blood glucose, blood lipids, and blood pressure; Table S1). 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 31 Covariates used in each study that included multivariable‐adjusted models are shown in Table S1. Detailed literature screening procedure is presented in Figure 1.…”

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

“…Leptin synthesis is induced to a lesser extent in macrophages and vascular smooth muscle cells (SMCs) by cytokines and AngII, resulting in local cardiovascular pathological conditions 18. Hyperleptinemia is a risk factor for symptomatic cardiovascular disease, mainly through increased arterial blood pressure, augmented oxidative stress, stiffening of the vascular wall, and vascular cell calcification 19, 20, 21, 22, 23…”