The Benefits of Regular Exercise
Those who exercise with regularity have a lower risk of type 2 diabetes (diabetes mellitus), cancer, hypertension, obesity, and the bone-destroying disease, osteoporosis, all of which are regarded as age-related dysfunctions. A recent study concluded that inactivity also influences the aging process.
Original Investigation, Source: the Archives of Internal Medicine, Vol. 168 (No. 2), Jan. 28th, 2008 Page 154 (abstract version with conclusion)
The Association between Physical Activity in Leisure Time and Leukocyte Telomere Length
By Lynn F. Cherkas, PhD.; Janice L. Hunkin, BSc; Bernet S. Kato, PhD.; J. Brent Richards, MD; Jeffrey P. Gardner, PhD.; Gabriela Surdulescu, MSc; Masayuki Kimura, MD, PhD.; Xiaobin Lu, MD; Tim D. Spector, MD, FRCP; Abraham Aviv, MD
Background: Physical inactivity is an important risk-factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past twelve months) is associated with leukocyte telomere length (LTL) in normal, healthy volunteers.
Methods: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders.
Results: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time. (P< .001).; this association remained significant after adjustment for age, sex, body-mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03).
Conclusions: A sedentary lifestyle (in addition to smoking, high body- mass index, and low socioeconomic status) has an effect on LTL, and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially anti-aging effect of regular exercise.
NEW from the Archives of Internal Medicine:
The Joint Effects of Physical Activity and Body Mass Index on Coronary Heart Disease Risk in Women
Arch Intern Med. 2008;168(8):884-890.
Background Physical activity and body mass index (calculated as weight in kilograms divided by height in meters squared) independently alter the risk of coronary heart disease (CHD); however, their combined effect on CHD is not established. Our objective was to study the combined association of physical activity and body mass index on CHD.
Methods Prospective cohort study of 38 987 women free of cardiovascular disease, cancer, and diabetes at baseline in the Women’s Health Study, with 10.9 mean years of follow-up. Weight, height, and recreational activities were reported on entry. Body mass index was categorized as normal weight (<25), overweight (25 to <30), and obese ( 30). Active was defined as 1000 kilocalories or more expended on recreational activities weekly. Six joint body weight–physical activity categories were defined. The main outcome measure was the occurrence of incident CHD during follow-up, defined as a cardiovascular event including nonfatal myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or CHD death.
Results A total of 948 cases of incident CHD occurred during follow-up. Higher body mass index and physical inactivity were individual predictors of CHD. In joint analyses, compared with active normal-weight individuals, the multivariate-adjusted hazard ratios (95% confidence intervals) were 1.54 (1.14-2.08) for overweight-active; 1.87 (1.29-2.71) for obese-active; 1.08 (0.84-1.39) for normal weight–inactive; 1.88 (1.46-2.42) for overweight-inactive; and 2.53 (1.94-3.30) for obese-inactive. Increasing levels of walking also resulted in significant reductions in CHD risk for overweight and obese individuals.
Conclusions The risk of CHD associated with elevated body mass index is considerably reduced by increased physical activity levels. However, the risk is not completely eliminated, reinforcing the importance of being lean and physically active.
Author Affiliations: Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center (Dr Weinstein), Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital (Drs Sesso, Lee, Rexrode, Cook, Manson, Buring, and Gaziano), and Department of Epidemiology, Harvard School of Public Health (Drs Lee, Manson, and Buring), Boston, Massachusetts.
In This Issue of Archives of Internal Medicine
Arch Intern Med. 2008;168(8):790.
Lee Levin, M.D. Doctor’s Office Recommended Reading
Dr. Levin would like to bring to your attention some articles relevant to successful aging, which were published in 2008.
From the Archives of Internal Medicine Volume 168 (No. 2), January 28th, 2008
Successful Aging: Is It in Our Future?
By Jack M. Guralnik, M.D. PhD
Arch Intern Med. 2008;168(2):Pages 131-132.
Cystatin-C and Aging Success
Author Affiliations: Department of Medicine, Tufts–New England Medical Center, Boston, Massachusetts (Drs Sarnak and Rifkin); Collaborative Health Studies Coordinating Center, Seattle, Washington (Drs Katz and Siscovick); Departments of Biostatistics (Dr Katz), Medicine (Drs Siscovick and Kestenbaum), and Epidemiology (Dr Siscovick), University of Washington, Seattle; Departments of Medicine (Drs Fried and Newman) and Epidemiology (Dr Newman), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Medicine, University of Maryland, Baltimore (Dr Seliger); Department of Pathology, University of Vermont College of Medicine, Burlington (Dr Tracy); and Department of Medicine, San Francisco Veterans Administration and University of California, San Francisco (Dr Shlipak).
Group Information: A list of participating Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org.
Methods We evaluated the relationship between cystatin C and aging success during a 6-year follow-up in the Cardiovascular Health Study, a community-based cohort of older adults (aged 65 years). Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and having intact physical and cognitive functioning. In adjusted analysis, an accelerated failure time model was used to evaluate the percentage reduction in successful years by level of cystatin C. A separate Cox proportional hazards model evaluated whether cystatin C was related to incident physical and cognitive disability.
Results A total of 2140 participants had cystatin C measured and were free of the previously mentioned conditions at baseline. Their mean age was 74 years. The mean cystatin C level, creatinine level, and estimated glomerular filtration rate were 1.06 mg/L, 0.93 mg/dL, and 78 mL/min/1.73 m2, respectively (to convert cystatin C to nanomoles per liter, multiply by 75; and to convert creatinine to micromoles per liter, multiply by 88.4). A total of 873 participants reached a first event in follow-up, 138 because of cognitive disability, 238 because of physical disability, 34 because of chronic obstructive pulmonary disease, 146 because of cancer, and 317 because of cardiovascular disease. The adjusted percentage reduction in successful life years in the highest vs the lowest quartile of cystatin C was 27% (95% confidence interval, 11%-39%). The highest vs lowest quartile of cystatin C also was independently associated with incident cognitive or physical disability (hazard ratio, 1.39; 95% confidence interval, 1.00-1.98).
Conclusion A higher cystatin C level, even within a range of relatively normal kidney function, was associated with unsuccessful aging.
More Anti-Aging News
From Internal Medicine News
Volume 41, Issue 11, Pages 1-2 (1 June 2008)
Low Vitamin D Tied To Poor Prognosis In Breast Cancer:
Significant Differences Seen at 10 Years
by SHARON WORCESTER (Southeast Bureau)
Vitamin D deficiency at the time of breast cancer diagnosis is common and is associated with a significantly increased risk of metastasis and mortality, according to data from a study of 512 women with newly diagnosed breast cancer.
The women were enrolled in the study at three University of Toronto hospitals between 1989 and 1995 and followed for a median of 11.6 years. Only 24% had adequate levels of vitamin D in the blood at diagnosis (greater than 72 nmol/L), 37.5% had insufficient levels (50–72 nmol/L), and 38.5% were vitamin D deficient (less than 50 nmol/L).
Women deficient in vitamin D were more likely to have high-grade cancer and were more likely to die from their breast cancer, Dr. Pamela Goodwin, lead study author, said during a teleconference about the study findings, which were released in advance of formal presentation of the research at the annual meeting of the American Society of Clinical Oncology.
After 10 years, 69% of those with vitamin D deficiency had metastases-free survival, compared with 83% of those with adequate levels of vitamin D at diagnosis (hazard ratio of 1.94, P = .02), and 74% of those with a deficiency were alive, compared with 85% of those with adequate levels (HR 1.73,P = .02), reported Dr. Goodwin of Mount Sinai Hospital in Toronto.
The associations between vitamin D deficiency and distant disease-free survival were independent of age, body mass index, insulin level, and tumor stage and grade, and were not significantly modified by estrogen receptor, adjuvant chemotherapy, or tamoxifen use. The associations between vitamin D deficiency and overall survival were attenuated by tumor grade and were absent in women with estrogen receptor-negative breast cancer, Dr. Goodwin said.
The women in the study had a mean age of 50 years. Low levels of vitamin D were associated with premenopausal status, high body mass index, high insulin levels, and low dietary intake of retinol, vitamin E, grains, and alcohol, she noted.
Additional studies are required before any conclusions can be drawn about a causal relationship between vitamin D deficiency and breast cancer development or prognosis. Should these findings be replicated in future studies, a randomized clinical trial examining the effects of vitamin D supplementation on outcomes in women with breast cancer would be warranted, Dr. Goodwin said. The results of an ongoing replication study are expected by the end of the year, she added.
Commenting on the current study findings, Dr. Julie Gralow, chair of the ASCO Cancer Communications Committee, called the results “fascinating,” and noted that this is the first study to suggest an association between vitamin D deficiency and outcomes following breast cancer diagnosis.
“As a clinician, I will be seeing breast cancer patients tomorrow … who will ask, ‘Should I correct vitamin D deficiency if I have one?’” added Dr. Gralow, a breast cancer specialist at the Fred Hutchinson Cancer Research Center at the University of Washington, Seattle.
At this time, it would be premature to recommend supplementation in the hopes that it might improve outcomes, she said, reiterating Dr. Goodwin’s conclusion that additional research is necessary before that can be said “with any degree of confidence,” Dr. Gralow said.
But other benefits of vitamin D, such as for bone health, may be reason enough to support supplementation “even if we can’t tell patients that it would have any benefit with respect to breast cancer,” she added.
In patients who desire such supplementation, it is important to first measure serum 25-hydroxyvitamin D levels to ensure they are healthy, because although the study wasn’t powered to determine statistical significance on this measure, it was observed that extremely high levels of vitamin D also might be associated with adverse outcomes, Dr. Goodwin reported.
From Internal Medicine News
Volume 41, Issue 7, Page 39 (1 April 2008)
Coronary Artery Calcium Predicts Cardiovascular Events
by BRUCE JANCIN (Denver Bureau)
SNOWMASS, COLO. —The most intriguing potential application for coronary artery calcium imaging is as a tool to track atherosclerosis progression over time in response to treatment, Dr. Matthew J. Budoff said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.
“I’m not suggesting that this is a current application, but the data now emerging are pretty interesting,” said Dr. Budoff, director of cardiac CT at Harbor-UCLA Medical Center, Torrance, Calif.
He cited an observational study by Dr. Paolo Raggi of Tulane University, New Orleans, and coinvestigators, who measured the change in coronary artery calcium (CAC) on serial electron-beam tomography scans in 495 statin-treated asymptomatic patients.
During up to 7 years of follow-up, 41 subjects had an acute MI. The relative risk of an MI was increased 17-fold in those with at least a 15% per year rise in CAC score. CAC progression provided incremental prognostic value beyond that associated with LDL cholesterol level, which was a mean of 118 mg/dL in patients who had an MI and a similar 122 mg/dL in those with no MI (Arterioscler. Thromb. Vasc. Biol. 2004;24:1272–7).
“This might be a way, in the future, of monitoring therapy. You’re on a statin, your LDL is pretty good, but your CAC is increasing—maybe we should do something more,” Dr. Budoff commented at the conference cosponsored by the American College of Cardiology.
He also described several current uses for CAC imaging:
▸ Screening asymptomatic patients with an intermediate Framingham risk score. Of asymptomatic adults, 40% fall into the Framingham intermediate-risk category, meaning they have an estimated 10%–20% risk of a coronary event within the next 10 years. Most acute MIs occur in this mid-risk group. Dr. Budoff was coauthor of a 2007 ACC/American Heart Association Clinical Expert Consensus Statement that endorsed CAC measurement as a means of identifing a higher-risk subgroup in whom aggressive primary preventive measures are warranted (J. Am. Coll. Cardiol. 2007;49:378–402).
The Multi-Ethnic Study of Atherosclerosis (MESA), a National Institutes of Health-sponsored prospective study of 6,814 patients followed for 3.5 years, was merely the most recent of several large studies showing that a CAC score of 100 or more was associated with a 10-fold increased risk of incident coronary heart disease (CHD).
Prior to MESA, Dr. Budoff conducted an observational study of 25,253 consecutive asymptomatic patients referred by their primary care physicians for CAC scanning. After adjustment for traditional cardiovascular risk factors, a baseline CAC of 100 or greater was associated with a 10.4-fold increased rate of all-cause mortality over the next 10 years, compared with a CAC of 0 (J. Am. Coll. Cardiol. 2007;49:1860–70).
And an NIH-sponsored prospective study of more than 10,700 asymptomatic individuals free of known CHD showed that a baseline CAC of 97–409 was associated with an adjusted 9.7-fold greater risk of nonfatal MI or CHD death in the next 3.5 years, compared with subjects with a CAC of 0 (Am. J. Epidemiol. 2005;162:421–9).
“A CAC greater than 100 is more robust as a predictor of future events than Framingham risk factors, which are traditionally in the realm of two- to threefold increased risk, and more robust than C-reactive protein or carotid intimal-medial thickness, where relative risks are in the 1.5–3 range,” said Dr. Budoff, who is on the speakers bureau for General Electric.
▸ Identification of very-low-risk patients needing no further evaluation for coronary artery disease. Four studies totaling nearly 6,000 patients indicate a CAC of 0 has a 95%–99% negative predictive value for obstructive coronary disease. A fifth study, by Dr. Budoff and co-investigators, concluded that a CAC score of 0 has at least a 5-year warranty before a repeat scan is appropriate because the likelihood of CAC progression during that period is so low (Int. J. Cardiol. 2007;117:227–31).
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Carnitine May Be Helpful for Fibromyalgia Patients
by Luke Curtis of The Human Ecologist
Carnitine is an amino acid that transports fatty acids into the mitochondria cells, and plays a critical role in many energy-producing and detoxification reactions. Several earlier studies have reported that supplemental carnitine or acetyl-carnitine may be helpful to fibromyalgia and chronic-fatigue patients. An Italian study of 102 fibromyalgia patients found that those patients given 1500 milligrams of supplemental acetyl-carnitine daily for 10 weeks had significantly less pain and significantly less depression than the fibromyalgia patients given placebo.–Rossini, M. et al. Double-blind, multicenter trial comparing l-carnitine with placebo in the treatment of fibromyalgia patients. Clinical and Experimental Rheumatology, 25 (2): 182-8, March-April 2007
The Study
Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients.
M Rossini, O Di Munno, G Valentini, G Bianchi, G Biasi, E Cacace, D Malesci, G La Montagna, O Viapiana, and S Adami
Clin Exp Rheumatol, March 1, 2007; 25(2): 182-8.
Authors and affiliation: Rossini M, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E, Malesci D, La Montagna G, Viapiana O, Adami S. Rheumatology Unit, University of Verona, Italy.
PMID: 17543140
Objective: Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue.
Several analgesic strategies have been evaluated but the results are moderate and inconsistent. Antidepressant agents are now considered the treatment of choice in most patients.
It has been recently suggested that FMS may be associated with metabolic alterations including a deficit of carnitine.
In this multicenter randomized clinical trial we evaluated the efficacy of acetyl L-carnitine (LAC) in patients with overt FMS.
Methods: 102 patients meeting the American College of Rheumatology criteria for FMS were randomized into the study. The treatment consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular (i.m.) injection of either 500 mg LAC or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either 500 mg LAC or placebo. The patients were seen during treatment after 2 (visit 3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment discontinuation (follow-up visit).
Outcome measures included the number of positive tender points, the sum of pain threshold (kg/cm2 or “total myalgic score”), the Short Form 36 (SF36), a 100 mm visual analog scale (VAS) for self-perceived stiffness, fatigue, tiredness on awakening, sleep, work status, depression, and muscular-skeletal pain, and the Hamilton depression scale.
Results: The “total myalgic score” and the number of positive tender points declined significantly and equally in both groups until the 6th week of treatment. At the 10th week both parameters remained unchanged in the placebo group but they continued to improve in the LAC group with a statistically significant between-group difference.
Most VAS scores significantly improved in both groups.
A statistically significant between-group difference was observed for depression and musculo-skeletal pain. Significantly larger improvements in SF36 questionnaire were observed in LAC than in placebo group for most parameters. Treatment was well-tolerated.
Conclusion: Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.
Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality Harald Dobnig, MD; Stefan Pilz, MD; Hubert Scharnagl, PhD; Wilfried Renner, PhD; Ursula Seelhorst, MA; Britta Wellnitz, LLD; Jürgen Kinkeldei, DEng; Bernhard O. Boehm, MD; Gisela Weihrauch, MSc; Winfried Maerz, MD
Arch Intern Med. 2008;168(12):1340-1349.
Background In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality.
Methods Prospective cohort study of 3258 consecutive male and female patients (mean [SD] age, 62 [10] years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths.
Results During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for all-cause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29-2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels).
Conclusions Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.
Author Affiliations: Division of Endocrinology and Nuclear Medicine, Department of Internal Medicine (Dr Dobnig), and Clinical Institute of Medical and Chemical Laboratory Diagnostics (Drs Scharnagl, Renner, and Maerz and Ms Weihrauch), Medical University of Graz, Graz, Austria; and Department of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Heidelberg (Dr Pilz), LURIC Study Nonprofit LLC, Freiburg (Ms Seelhorst and Dr Wellnitz), Synlab Center of Laboratory Diagnostics Stuttgart, Leinfelden-Echterdingen (Dr Kinkeldei), Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Ulm, Ulm (Dr Boehm), and Synlab Center of Laboratory Diagnostics Heidelberg, Eppelheim (Dr Maerz), Germany.
