A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.

BACKGROUND: Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PlA2, of the gene encoding glycoprotein IIIa in kindreds with a high prevalence of premature myocardial infarction. METHODS: To investigate the relation between the PlA2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infarction or unstable angina and 68 inpatient controls without known heart disease. The groups were matched for age, race, and sex. We used two methods to determine the PlA genotype: reverse dot blot hybridization and allele-specific restriction digestion. RESULTS: The prevalence of PlA2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P=0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of PlA2 was 50 percent, a value that was 3.6 times that among control subjects under 60 years of age (13.9 percent, P=0.002). Among subjects with the PlA2 polymorphism, the odds ratio for having a coronary event was 2.8 (95 percent confidence interval, 1.2 to 6.4). In the patients less than 60 years of age at the onset of disease, the odds ratio was 6.2 (95 percent confidence interval, 1.8 to 22.4). CONCLUSIONS: We observed a strong association between the PlA2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years

Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla

Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30–45 minutes after administration of the contrast agent

Decreased coronary artery distensibility measured using 3T MRI is related to systemic inflammation in patients with coronary artery disease

We previously reported that coronary distensibility can be measured non-invasively using 3T MRI and that distensibility is reduced in coronary artery disease (CAD) patients compared with healthy subjects. Because atherosclerotic vascular disease is an inflammatory process, we sought to test the hypothesis that coronary distensibility measured with MRI is associated with systemic inflammation, measured by serum high sensitivity C reactive protein, hsCRP, a marker of increased inflammation, and adiponectin, a fat hormone associated with decreased inflammation, in healthy subjects and in CAD patients

Vitamin D deficiency is associated with development of subclinical coronary artery disease in HIV-infected African American cocaine users with low Framingham-defined cardiovascular risk

Chronic cocaine use may lead to premature atherosclerosis, but the prevalence of and risk factors for coronary artery disease (CAD) in asymptomatic cocaine users have not been reported. The objective of this study was to examine whether vitamin D deficiency is associated with the development of CAD in human immunodeficiency virus (HIV)-infected African American cocaine users with low CAD risk. METHODS: In this prospective follow-up study, we investigated 169 HIV-infected African American cocaine users with low Framingham risk at baseline. The main outcome measures were incidence of subclinical CAD and development of subclinical CAD. RESULTS: Fifty of the 169 African Americans had evidence of subclinical disease on the initial cardiac computed tomography. A second cardiac computed tomography was performed on the 119 African Americans without disease on the first scan. The total sum of person-years of follow-up was 289.6. Subclinical CAD was detected in 11 of these, yielding an overall incidence of 3.80/100 person-years (95% confidence interval 1.90–6.80). Among the factors investigated, only vitamin D deficiency was independently associated with development of subclinical CAD. The study did not find significant associations between CD4 count, HIV viral load, or antiretroviral treatment use and the incidence of subclinical CAD. This study appears to suggest that there is a threshold level of vitamin D (10 ng/mL) above which the effect of vitamin D on subclinical CAD is diminished. CONCLUSION: The incidence of subclinical CAD in HIV-infected African American cocaine users with low CAD risk is high, especially in those with vitamin D deficiency. Well designed randomized clinical trials are warranted to confirm the role of vitamin D deficiency in the development of CAD in HIV-infected African American cocaine users with low CAD risk

Sarcopenia and Cardiovascular Diseases

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be particularly important among those with chronic disease states. Early recognition of sarcopenia is important because it can provide an opportunity for interventions to reverse or delay the progression of muscle disorder, which may ultimately impact cardiovascular outcomes. Relying on body mass index is not useful for screening because many patients will have sarcopenic obesity, a particularly important phenotype among older cardiac patients. In this review, we aimed to: (1) provide a definition of sarcopenia within the context of muscle wasting disorders; (2) summarize the associations between sarcopenia and different cardiovascular diseases; (3) highlight an approach for a diagnostic evaluation; (4) discuss management strategies for sarcopenia; and (5) outline key gaps in knowledge with implications for the future of the field