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Serum inflammatory markers correlate with outcome and response to therapy in subjects with cardiovascular disease. However, current individual markers lack specificity for the diagnosis of coronary artery disease (CAD). We hypothesize that a multimarker proteomic approach measuring serum levels of vascular derived inflammatory biomarkers could reveal a "signature of disease" that can serve as a highly accurate method to assess for the presence of coronary atherosclerosis. We simultaneously measured serum levels of seven chemokines [CXCL10 (IP-10), CCL11 (eotaxin), CCL3 (MIP1 alpha), CCL2 (MCP1), CCL8 (MCP2), CCL7 (MCP3), and CCL13 (MCP4)] in 48 subjects with clinically significant CAD ("cases") and 44 controls from the ADVANCE Study. We applied three classification algorithms to identify the combination of variables that would best predict case-control status and assessed the diagnostic performance of these models with receiver operating characteristic (ROC) curves. The serum levels of six chemokines were significantly higher in cases compared with controls (P < 0.05). All three classification algorithms entered three chemokines in their final model, and only logistic regression selected clinical variables. Logistic regression produced the highest ROC of the three algorithms (AUC = 0.95; SE = 0.03), which was markedly better than the AUC for the logistic regression model of traditional risk factors of CAD without (AUC = 0.67; SE = 0.06) or with CRP (AUC = 0.68; SE = 0.06). A combination of serum levels of multiple chemokines identifies subjects with clinically significant atherosclerotic heart disease with a very high degree of accuracy. These results need to be replicated in larger cross-sectional studies and their prognostic value explored.

Peripheral arterial disease (PAD) is characterized by reduced blood flow to the limbs, usually as a consequence of atherosclerosis, and affects approximately 12 million Americans. It is a common cause of cardiovascular morbidity and an independent predictor of cardiovascular mortality. Similar to other atherosclerotic diseases, such as coronary artery disease, PAD is the result of the complex interplay between injurious environmental stimuli and genetic predisposing factors of the host. Genetic susceptibility to PAD is likely contributed by sequence variants in multiple genes, each with modest effects. Although many of these variants probably alter susceptibility both to PAD and to coronary artery disease, it is likely that there exists a set of variants specifically to alter susceptibility to PAD. Despite the prevalence of PAD and its high societal burden, relatively little is known about such genetic variants. This review summarizes our limited present knowledge and gives an overview of recent, more powerful approaches to elucidating the genetic basis of PAD. We discuss the advantages and limitations of genetic studies and highlight the need for collaborative networks of PAD investigators for shedding light on this dark corner of vascular biology.

Objective: Established determinants of left ventricular (LV) mass explain only a modest fraction of its variability. Family studies to date suggest that a proportion of the unexplained variability can be accounted for by additive polygenic effects. An estimate of this proportion has not been reported previously in an East Asian population. The objective of this study was to estimate the heritability of LV mass in Japanese families living in Hawaii., Design and Methods: We analyzed data by components of variance in a sample of 169 hypertensive families (n = 476 subjects) and, separately, in a population-based sample of 256 families (n = 501 subjects) participating in the Honolulu Heart Program., Results: In multivariate models, established predictors of LV mass explained about half the total variance of LV mass. Using SOLAR, our estimates of the narrow sense heritability of LV mass ranged from 42.5% (SE 9.8, P < 0.0001) in our sample of hypertensive families to 60.6% (SE 11.7, P < 0.0001) in our population-based sample of families. Parametric bootstrap analyses confirmed that the inference for each sample was appropriate., Conclusions: Assuming the absence of shared familial environmental effects, close to half of the unexplained variance of LV mass in Japanese subjects living in Hawaii is genetic in nature. This estimate was observed in two independent samples. Therefore, the pursuit of novel genetic determinants of LV mass through either whole genome or candidate gene association studies of this population may be worthwhile. Such studies are certainly feasible.

Background: Asthma patients may be at increased risk of cardiovascular outcomes due to hypoxemia from asthma exacerbations and bronchodilator-induced tachycardia. We investigated whether inhaled corticosteroids, which are known to improve asthma control and reduce exacerbations, are associated with a lower rate of myocardial infarction., Methods: We used the Saskatchewan Health databases to form a population-based cohort of subjects aged 5 to 44 years who were using antiasthma drugs between 1975 and 1991. Subjects were followed until 1997, the age of 55 years, or death. A nested case-control approach was used where each subject with a first myocardial infarction was matched on calendar time, age, and sex with up to 10 controls randomly selected from the cohort., Results: The cohort consisted of 30,569 subjects, including 105 patients with myocardial infarction who were matched with 933 controls. The adjusted rate ratio of myocardial infarction for inhaled corticosteroid use during the year before the index date was 0.56 (95% confidence interval [CI]: 0.32 to 0.99) as compared with no use. Myocardial infarction decreased by 12% (95% CI: 0% to 23%) with each additional canister used during this 1-year period. The rate ratio of myocardial infarction for inhaled corticosteroid use was 0.78 (95% CI: 0.41 to 1.51) among patients with milder asthma and 0.19 (95% CI: 0.04 to 0.97) among those with more severe asthma., Conclusion: Inhaled corticosteroid use may reduce the risk of myocardial infarction in asthma patients, particularly those with more severe disease.