A susceptibility locus for coronary artery disease (CAD) at chromosome 9p21 has recently been reported, which may influence the age of onset of CAD. We sought to replicate these findings among white subjects and to examine whether these results are consistent with other racial/ethnic groups by genotyping three single nucleotide polymorphisms (SNPs) in the risk interval in the Atherosclerotic Disease, Vascular Function, and Genetic Epidemiology (ADVANCE) study. One or more of these SNPs was associated with clinical CAD in whites, U.S. Hispanics and U.S. East Asians. None of the SNPs were associated with CAD in African Americans although the power to detect an odds ratio (OR) in this group equivalent to that seen in whites was only 24–30%. ORs were higher in Hispanics and East Asians and lower in African Americans, but in all groups the 95% confidence intervals overlapped with ORs observed in whites. High-risk alleles were also associated with increased coronary artery calcification in controls and the magnitude of these associations by racial/ethnic group closely mirrored the magnitude observed for clinical CAD. Unexpectedly, we noted significant genotype frequency differences between male and female cases (P = 0.003–0.05). Consequently, men tended towards a recessive and women tended towards a dominant mode of inheritance. Finally, an effect of genotype on the age of onset of CAD was detected but only in men carrying two versus one or no copy of the high-risk allele and presenting with CAD at age >50 years. Further investigations in other populations are needed to confirm or refute our findings.

Objective: To investigate coronary heart disease (CHD) morbidity and mortality and their patterning by socioeconomic status among diabetic and nondiabetic individuals in Finland.

Methods: All diabetic persons aged 35-74 years entitled to free anti-diabetic medication were drawn from the 1991-1996 national health insurance files along with nondiabetic referents. Outcome events for up to 6 years of follow-up, corresponding to 418,987 and 867,813 person-years in diabetic and nondiabetic people, respectively, were identified from national health insurance, hospital discharge and causes of death registers using personal identification codes.

Results: The annual CHD incidence for diabetic women and men was 2.7% and 3.7%, respectively, corresponding to relative risks of 3.55 (95% CI: 3.43-3.67) and 2.64 (95% CI: 2.56-2.72) compared to nondiabetic persons. The impact of diabetes on CHD mortality was greater, with relative death rates of 6.04 and 3.42 for women and men, respectively. CHD mortality and incidence displayed systematic socioeconomic trends with higher rates among worse-off diabetic and nondiabetic people, although gradients were generally steeper for nondiabetics. In the diabetic population, socioeconomic differences were rather similar for sudden CHD deaths and nonfatal CHD incident cases. For both genders, socioeconomic differences in mortality after CHD diagnosis were small in both diabetic and nondiabetic persons, except for the lowest compared to the highest income quintile.

Conclusions: Socioeconomic CHD mortality differences among diabetic people in Finland were mainly explained by higher CHD incidence and particularly sudden deaths without prior CHD diagnosis. No systematic socioeconomic differences were found in long-term prognosis after CHD diagnosis.

BACKGROUND: Small asymptomatic lung nodules are found frequently in the course of cardiac computed tomography (CT) scanning. However, the utility of assessing and reporting incidental findings in healthy, asymptomatic subjects is unknown.

METHODS: The sample comprised 1023 60- to 69-year-old subjects free of clinical cardiovascular disease and cancer who participated in the Atherosclerotic Disease, VAscular functioN and genetiC Epidemiology Study. All subjects underwent cardiac CT for determination of coronary calcium between 2001 and 2004, and the first 459 subjects were assessed for incidental pulmonary findings. We used health plan clinical databases to ascertain 24-month health care use and clinical outcomes.

RESULTS: Noncalcified pulmonary nodules were reported in 81 of 459 subjects (18%). Chest CT was performed on 78% of participants in the 24 months after notification, compared with 2.5% in the previous 24 months. Chest x-ray use increased from 28% to 49%. The mean number of chest CT scans per subject was 1.3 (range, 0-5). Although no malignant lesions were diagnosed in the group who had pulmonary findings read, 1 lung cancer case was diagnosed in the group who did not have lung findings read. Among the 63 participants followed up by CT, the original lesion was not identified in 22 participants (35%), the lesion had decreased or remained stable in 39 participants (62%), and there was interval growth in 2 participants (3%).

CONCLUSION: Reporting noncalcified pulmonary nodules resulted in substantial rescanning that overwhelmingly revealed resolution or stability of pulmonary nodules, arguing for benign processes.

BACKGROUND: Diabetes mellitus is common, costly, and increasingly prevalent. Despite innovations in therapy, little is known about patterns and costs of drug treatment.

METHODS: We used the National Disease and Therapeutic Index to analyze medications prescribed between 1994 and 2007 for all US office visits among patients 35 years and older with type 2 diabetes. We used the National Prescription Audit to assess medication costs between 2001 and 2007.

RESULTS: The estimated number of patient visits for treated diabetes increased from 25 million (95% confidence interval [CI], 23 million to 27 million) in 1994 to 36 million (95% CI, 34 million to 38 million) by 2007. The mean number of diabetes medications per treated patient increased from 1.14 (95% CI, 1.06-1.22) in 1994 to 1.63 (1.54-1.72) in 2007. Monotherapy declined from 82% (95% CI, 75%-89%) of visits during which a treatment was used in 1994 to 47% (43%-51%) in 2007. Insulin use decreased from 38% of treatment visits in 1994 to a nadir of 25% in 2000 and then increased to 28% in 2007. Sulfonylurea use decreased from 67% of treatment visits in 1994 to 34% in 2007. By 2007, biguanides (54% of treatment visits) and glitazones (thiazolidinediones) (28%) were leading therapeutic classes. Increasing use of glitazones, newer insulins, sitagliptin phosphate, and exenatide largely accounted for recent increases in the mean cost per prescription ($56 in 2001 to $76 in 2007) and aggregate drug expenditures ($6.7 billion in 2001 to $12.5 billion in 2007).

CONCLUSIONS: Increasingly complex and costly diabetes treatments are being applied to an increasing population. The magnitude of these rapid changes raises concerns about whether these more costly therapies will result in proportionately improved outcomes.

Background: Although the number of infected people receiving highly active anti-retroviral therapy (HAART) in low- and middle- income countries increased dramatically, optimal disease management is not well defined.

Methods: We developed a model to compare the costs and benefits of three types of Human Immunodeficiency Virus monitoring strategies: symptom-based strategies, CD4-based strategies, and CD4 plus viral load strategies for starting, switching, and stopping HAART. We used clinical and cost data from southern Africa and performed a cost-effectiveness analysis. All assumptions were tested in sensitivity analyses.

Results: Compared to the symptom-based approaches, monitoring CD4 every 6 months and starting treatment at a threshold of 200 cells/μl was associated with a life expectancy gain of 6.5 months (61.9 vs. 68.4) and a discounted lifetime cost savings of $464 per person (4,069 vs. 3,605 discounted 2007 USD). CD4-based strategies where treatment was started at the higher threshold of 350 cells/μl provided an additional life expectancy gain of 5.3 months at a cost effectiveness of $107 per life-year gained compared to a threshold of 200 cells/μl. Monitoring viral load with CD4 was more expensive than monitoring CD4 alone, added 2.0 months of life, and had an incremental cost-effectiveness ratio of $5,414/life-year gained relative to monitoring CD4 counts. In sensitivity analyses, the cost-savings from CD4 monitoring compared to symptom-based approaches was sensitive to cost of inpatient care, and the cost-effectiveness of viral load monitoring was influenced by the per-test costs and rates of virologic failure.

Conclusions: Use of CD4 monitoring and early HAART initiation in southern Africa provides large health benefits relative to symptom-based approaches for HAART management. In southern African countries with relatively high costs of hospitalization, CD4 monitoring would likely reduce total health care expenditures. The cost-effectiveness of viral load monitoring depends on test prices and rates of virologic failure.