Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy.

BACKGROUND: Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients. RESULTS: The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications. CONCLUSION: In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

Improvement in psychosocial functioning during an intensive cardiovascular lifestyle modification program.

PURPOSE: Psychosocial factors have significant effects on development and progression of coronary artery disease (CAD), but appropriate strategies for clinical management of multiple risk factors in persons with CAD are not well defined. This study evaluated changes in psychosocial functioning in patients with cardiovascular disease participating in an intensive lifestyle modification program. METHODS: One hundred seventy-six patients participated in a prospective, nonrandomized intervention designed to stabilize or reverse progression of CAD through dietary changes, exercise, stress management, and group support. Three examinations over the course of 1 year assessed psychosocial functioning, physiological and biochemical CAD risk factors, and risk for future coronary events. RESULTS: Most patients showed significant improvements in mental health and quality of life as well as significant reductions in traditional CAD risk factors and cardiovascular risk. The intervention was effective in producing clinically meaningful changes in psychosocial functioning. Response rates were approximately 90% for clinical depression, 85% for stress, and 87% for mental health. CONCLUSIONS: A comprehensive lifestyle intervention can reduce multiple psychometric risk factors and produce clinically relevant improvement in measures of depression, stress, and mental health. Cardiac rehabilitation programs that effectively address psychosocial and physiological outcomes may be valuable alternatives or supplements to pharmacologic treatments for reducing multiple psychosocial risk factors for CAD.

Allelic imbalance in primary breast carcinomas and metastatic tumors of the axillary lymph nodes.

Axillary lymph node status is the most important prognostic factor in predicting disease outcome in women with breast cancer. A number of chromosomal aberrations in primary breast tumors have been correlated with lymph node status and clinical outcome, but chromosomal changes particular to metastatic lymph node tumors have not been well studied. DNA samples isolated from laser-microdissected primary breast and metastatic axillary lymph node tumors from 25 women with invasive breast cancer were amplified using 52 microsatellite markers defining 26 chromosomal regions commonly deleted in breast cancer. Levels and patterns of allelic imbalance (AI) within and between breast and lymph node tumors were assessed to identify chromosomal alterations unique to primary or metastatic tumors and to examine the timing of metastatic potential. The overall frequency of AI in primary breast tumors (0.24) was significantly greater (P < 0.001) than that in lymph node tumors (0.10), and congruent AI events were observed for < 20% of informative markers. AI at chromosomes 11q23.3 and 17p13.3 occurred significantly more frequently (P < 0.05) in primary breast tumors alone; no chromosomal regions showed a significantly higher AI frequency in lymph nodes. Higher rates of AI in primary versus metastatic lymph node tumors suggest that acquisition of metastatic potential may be an early event in carcinogenesis, occurring before significant levels of AI accumulate in the primary tumor. In addition, patterns of AI were highly discordant between tumor types, suggesting that additional genetic alterations accumulated independently in the two cell populations.