Background— High-sensitivity C-reactive protein (CRP) has been investigated extensively as a marker for predicting the risk of cardiovascular disease (CVD). CVD accounts for a large proportion of mortality and morbidity in American Indians; we sought to test the association of CRP and CVD in a population-based American Indian cohort 45 to 74 years old. Methods and Results— Of 3277 participants who were CVD-free at baseline, 542 had CRP >10 mg/L and were excluded from analysis; 50.1% of those included had diabetes. There were 343 CVD events among this cohort during a median follow-up of 6.2 years. Multiple CVD risk factors were used as covariates in Cox proportional-hazard models. After exclusions, the median CRP (3.2 mg/L) was higher than reported in many other populations. CRP predicted CVD in models adjusted for traditional risk factors, but not when albuminuria and fibrinogen were included. In subgroup analysis, CRP was strongly related to incident CVD among nondiabetic women participants, even after adjustment for traditional CVD risk factors and other indicators of inflammation. Conversely, CRP was elevated beyond the useful range of the American Heart Association/Centers for Disease Control and Prevention clinical guidelines in 16% of this population, and CRP was not predictive of CVD in important subgroups, such as those with diabetes. Conclusions— CRP was a predictor of CVD in this American Indian population with a high prevalence of diabetes and other risk factors. The predictive ability of CRP varies considerably among subgroups with different risk factor profiles.

Background— Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD. Methods and Results— We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined. The frequency of a composite genotype that conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls without CAD. A conditional logistic regression model indicated a univariate OR for CAD of 2.3 (95% CI 1.3 to 4.2, P =0.005) for the variant genotypes. After adjustment for demographic and CAD risk factors, including type 2 diabetes mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5 to 7.0, P =0.004). Conclusions— Variant MBL genotypes coding for markedly diminished levels of MBL are predictive of CAD. After adjustment for multiple traditional risk factors for ischemic heart disease, this association remains significant. A high prevalence of variant MBL alleles and CAD in this population suggests that potentially important public health benefits may accrue from future interventions based on these genotypes.

Background: Myocardial energetic efficiency (MEE), is a strong predictor of CV events in hypertensive patient and is reduced in patients with diabetes and metabolic syndrome. We hypothesized that severity of insulin resistance (by HOMA-IR) negatively influences MEE in participants from the Strong Heart Study (SHS). Methods: We selected non-diabetic participants (n = 3128, 47 ± 17 years, 1807 women, 1447 obese, 870 hypertensive) free of cardiovascular (CV) disease, by merging two cohorts (Strong Heart Study and Strong Heart Family Study, age range 18–93). MEE was estimated as stroke work (SW = systolic blood pressure [SBP] × stroke volume [SV])/“double product” of SBP × heart rate (HR), as an estimate of O₂ consumption, which can be simplified as SV/HR ratio and expressed in ml/sec. Due to the strong correlation, MEE was normalized by left ventricular (LV) mass (MEEi). Results: Linear trend analyses showed that with increasing quartiles of HOMA-IR patients were older, more likely to be women, obese and hypertensive, with a trend toward a worse lipid profile (all p for trend < 0.001), progressive increase in LV mass index, stroke index and cardiac index and decline of wall mechanics (all p < 0.0001). In multivariable regression, after adjusting for confounders, and including a kinship coefficient to correct for relatedness, MEEi was negatively associated with HOMA-IR, independently of significant associations with age, sex, blood pressure, lipid profile and central obesity (all p < 0.0001). Conclusions: Severity of insulin resistance has significant and independent negative impact on myocardial mechano-energetic efficiency in nondiabetic individual from a population study of American Indians. Trial registration number NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988