Publications

BACKGROUND

Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) are potential novel therapies after myocardial infarction (MI). We first established the optimal and clinically applicable dosages of these drugs in mobilizing hematopoietic stem cells (HSC), and then tested the efficacy of monotherapy and combination therapy post-MI.

METHODS AND RESULTS

Optimal doses were established in enhanced green fluorescent protein (eGFP) + chimeric mice (n = 30). Next, mice underwent MI and randomized into 4 groups (n = 18/group): 1) GCSF; 2) EPO; 3) EPO+GCSF; and 4) control. Left ventricular (LV) function was analyzed pre-MI, at 4 hours and at 28 days post-MI. Histological assessment of infarct size, blood vessels, apoptotic cardiomyocytes, and engraftment of eGFP+ mobilized cells were analyzed at day 28. LV function in the control group continued to deteriorate, whereas all treatments showed stabilization. The treatment groups resulted in less scarring, increased numbers of mobilized cells to the infarct border zone (BZ), and a reduction in the number of apoptotic cardiomyocytes. Both EPO groups had significantly more capillaries and arterioles at the BZ.

CONCLUSION

We have established the optimal doses for EPO and GCSF in mobilizing HSC from the bone marrow and demonstrated that therapy with these agents, either as monotherapy or combination therapy, led to improvement of cardiac function post-MI. Combination therapy does not seem to have additive benefit over monotherapy in this model.

BACKGROUND

Individuals with exaggerated exercise blood pressure (BP) tend to develop future hypertension. It is controversial whether they have higher risk of death from cardiovascular disease (CVD).

METHODS AND RESULTS

A total of 6578 asymptomatic Lipid Research Clinics Prevalence Study participants (45% women; mean age, 46 years; 74% with untreated baseline BP <140/90 mm Hg [nonhypertensive]) performing submaximal Bruce treadmill tests were followed for 20 years (385 CVD deaths occurred). Systolic and diastolic BP at rest, Bruce stage 2, and maximal BP during exercise were significantly associated with CVD death. When we compared multivariate hazard ratios and 95% confidence intervals per 10/5-mm Hg BP increments, the association was strongest for rest BP (systolic, 1.21 [1.14 to 1.27]; diastolic, 1.20 [1.14 to 1.26]), then Bruce stage 2 BP (systolic, 1.09 [1.04 to 1.14]; diastolic, 1.09 [1.05 to 1.13]), then maximal exercise BP (systolic, 1.06 [1.01 to 1.10]; diastolic, 1.04 [1.01 to 1.08]). Overall, exercise BP was not significant after adjustment for rest BP. However, hypertension status modified the risk associated with exercise BP (P(interaction)=0.03). Among nonhypertensives, whether they had normal BP (<120/80 mm Hg) or prehypertension, Bruce stage 2 BP >180/90 versus < or =180/90 mm Hg carried increased risk independent of rest BP and risk factors (adjusted hazard ratio for systolic, 1.96 [1.40 to 2.74], P<0.001; diastolic, 1.48 [1.06 to 2.06], P=0.02) and added predictive value (net reclassification improvement, systolic, 12.0% [-0.1% to 24.2%]; diastolic, 9.9% [-0.3% to 20.0%]; relative integrated discrimination improvement, 14.3% and 12.0%, respectively).

CONCLUSIONS

In asymptomatic individuals, elevated exercise BP carried higher risk of CVD death but became nonsignificant after accounting for rest BP. However, Bruce stage 2 BP >180/90 mm Hg identified nonhypertensive individuals at higher risk of CVD death.

Injection drug use is an ongoing public health crisis in China and one of the largest contributors to the transmission of HIV/AIDS. Though the government has rapidly scaled up methadone maintenance treatment clinics, they have not been extensively evaluated to analyze factors influencing rates of attendance. We explored the facilitators and barriers to accessing methadone maintenance clinics in Kunming City, Yunnan Province, China. Using in-depth qualitative interviews conducted from February 2008 to June 2008 with 35 informants - injection drug users (IDUs) and key stakeholders - we explored factors that determine whether drug users decide to present at methadone clinics. Interviews were digitally recorded with consent, transcribed verbatim, and translated. Content analysis was conducted to identify themes which included general attitudes toward methadone treatment, barriers and challenges to access, and suggestions for improvement. Within these, topics included responses to methadone, its side effects, and fear of discrimination, loss of privacy, and police interference. Respondents also listed numerous suggestions for improvement including raising awareness of harm reduction both among drug users and the community, providing additional support in the form of psychological counseling, job training and behavioral therapy, and increasing communication between police, government, and public health officials. High rates of HIV infection among IDUs in China have prompted public health responses including the scale up of methadone maintenance clinics. Our results may inform policy strategists in implementing social-structural changes to create enabling environments that facilitate an increase in access to methadone clinics among IDUs in Kunming.