Jewish World Review April 28, 2003 / 26 Nissan, 5763

C-reactive Protein & Stroke

By Robert A. Wascher, M.D., F.A.C.S. | Elevate blood levels of C-reactive protein (CRP) have been linked to an increase in the risk of cardiovascular disease, as I have previously reported in this column. A new study in the current issue of the journal Circulation now suggests that this inflammatory protein may also play a role in the development of at least some strokes. Previous studies have demonstrated an association between CRP levels and the risk of stroke, but most of these studies have looked at patients with multiple additional risk factors for stroke. In this study, the participants were carefully stratified according to other risk factors for stroke, as well as based upon the CRP levels in their blood.

The study evaluated 259 male patients who had previously experienced at least one stroke, as well as 1,348 control male patients without a history of stroke. All of these study participants had undergone measurements of CRP blood levels 20 years prior to the completion of the study's observation period. At the time when CRP levels were measured, the volunteers were 48 to 70 years of age. The researchers then studied the relationships between initial baseline CRP levels and the subsequent incidence of strokes.

Overall, within 10 to 15 years of CRP testing, the volunteers with the highest blood levels of CRP experienced a nearly four-fold increase in the risk of stroke. Among the men without a history of high blood pressure or diabetes, high CRP levels were associated with a nearly two-fold increase in the risk of stroke. Among men who had the highest CRP levels at or before 55 years of age, the risk of stroke was about three-fold higher when compared to their same-age peers with the lowest CRP levels.

Finally, among nonsmokers with the highest CRP levels, the risk of stroke was nearly six times as great when compared with the nonsmokers with the lowest CRP levels. Among men with a history of smoking, high blood pressure, diabetes, or age greater than 55 years, there was no additive increase in the risk of stroke with elevated CRP levels.

This study provides an interesting look at the effects of high CRP levels on the risk of stroke in men with and without concomitant risk factors for this often lethal neurological disease. These results strongly suggest that a high blood concentration of CRP is, in and of itself, a significant risk factor for stroke (as well as cardiovascular disease in general), at least in middle-aged men. When other risk factors for stroke are also present (such as advanced age, high blood pressure, diabetes or smoking), the association between elevated CRP levels and stroke was no longer significant. This study adds additional evidence that CRP levels in the blood should be measured on a regular basis, at least among those approaching middle age, and much as cholesterol, HDL and LDL levels have been routinely measured during annual physical exams for many years now.


Recent studies have called into question the safety of long-term hormone replacement therapy (HRT) following menopause. Chronic use of HRT has been linked to an increase in the risk of breast and other cancers, as well as an increased risk of cardiovascular disease and stroke. Many women are, therefore, rethinking their use of HRT. However, one clear positive effect associated with HRT is a reduction in the risk of osteoporosis ("thinning of the bones").

As I have previously reported in this column, and as I will extensively elaborate upon further in a forthcoming book on the subject, the apparent health benefits of HRT now appear to be quite limited, while the detrimental effects of prolonged HRT appear to be quite substantial, potentially. I have been telling my own patients, for some time now, that the choice regarding HRT is theirs to make.

I see my role in the HRT debate as that of an educator and patient advocate. As long as each patient understands the risks and benefits of HRT, I leave it up to them to decide. When they ask me, specifically, about the risks of developing osteoporosis if they discontinue their HRT, I remind them that there are a number of very good alternatives to HRT that may reduce their risk of bone loss during their postmenopausal years.

Among the most effective alternatives is a class of medication known as the bisphosphonates. These drugs work by inhibiting bone cells, called osteoclasts, which normally reabsorb mineralized bone. The bisphosphonates have come into relatively wide use to prevent osteoporosis in postmenopausal women, and have been especially useful in treating the painful skeletal metastases that are commonly seen in breast, prostate and other cancers.

Moreover, the bisphosphonates are also the only class of drugs that appear to be able to restore, to some extent, lost bone after osteoporosis has already developed.

While bisphosphonates have been rather extensively studied in patients with osteoporosis and skeletal metastatic cancers, its use as an alternative to HRT has been less well researched. An interesting study in the current issue of the Archives of Internal Medicine performed a multicenter, international, randomized, blinded evaluation of 144 postmenopausal women who had recently discontinued HRT, and who had clinical evidence of reduced bone mineral density (osteoporosis). The patients were randomized to receive the bisphosphonate alendronate or a placebo (sugar pill), and all patients were subsequently followed for one year. Bone mineral density examination results, biochemical markers of bone loss, and tolerability of treatment were assessed at the end of the study period.

At the end of one year, the women who received alendronate had an average increase in bone density of 2.3%, while the women who received the placebo pill experienced an average bone mineral density loss of 3.2%, for a relative difference between alendronate and placebo of 5.5%. Biochemical blood tests also confirmed that the women receiving alendronate experienced a significant reduction in bone turnover, while the placebo group experienced an increase in bone turnover.

Alendronate was well-tolerated, and no significant difference between the two patient groups was identified in terms of side effects or toxicity.

Thus, this study showed that the bisphosphonate alendronate increased or maintained bone mineral density in women who recently discontinued HRT, while the women who stopped their HRT, but did not take alendronate, experienced a significant loss of bone density. In my view, the risks of long-term HRT use are significant, and the benefits of such treatment are few.

While I risk the wrath of some women (and their partners, perhaps...) who have relied upon HRT to eliminate the night sweats, chills, and the emotional roller coaster that are occasionally associated with menopause, the scientific evidence is quite compelling: long-term HRT poses a significant potential risk to the health and well-being of women, and these risks begin to become statistically significant after more than 5 years of HRT. This study confirms that superior non-HRT alternatives are available to treat some of the same ailments that HRT has long been prescribed for.


While SARS has received a great deal of attention lately, there is a more pervasive and seemingly silent epidemic that is sweeping across the land. More than half of all Americans have already been afflicted with at least a mild case of this condition, and many of them will die prematurely due to the deleterious effects of this condition. This medical condition is, of course, obesity. We know that the risks of cardiovascular disease, stroke, high blood pressure, diabetes, arthritis, and respiratory disease, as well as other potentially life-threatening ailments, are more common in obese people. There has also been some scientific evidence that certain cancers may also be more common in significantly overweight people, including cancers of the breast, prostate, uterus, pancreas and, possibly, the colon. However, other studies have failed to show a strong link between obesity and an increased risk of cancer.

In this week's New England Journal of Medicine is a study that looked at more than 900,000 American adults, starting in 1982. All study volunteers were clinically free of cancer at the beginning of the study, but over an average of 16 years of follow-up, 57,145 of these study patients developed cancer. The study's authors then statistically analyzed the correlation between body mass index (BMI) at the onset of the study and the subsequent development of various cancers in men and women. The study found that the men in the highest BMI category (at least 40) had a 52% higher incidence of cancer deaths, while the women in the highest BMI category experienced a 62% increase in the risk of dying of cancer (both groups were compared with men and women, respectively, with normal BMI values).

Specific cancers that occurred more frequently among the most obese patients included cancers of the esophagus, colon/rectum, liver, gallbladder, pancreas and kidney. There was also an increase in the risk of dying from non-Hodgkin's lymphoma and multiple myeloma. Significant trends toward death due to cancer in the very obese also included cancers of the stomach and prostate gland in men, and cancers of the breast, uterus, cervix and ovaries in women.

Following statistical analysis to account for other associated risk factors for cancer in this large group of patients, the authors concluded that the current extent of overweight and obesity in the United States could account for as many as 14% of all cancer deaths among men, and 20% of cancer deaths among women. These are sobering statistics, and should provide further impetus for all of us to watch what we eat, and to incorporate regular aerobic exercise into our busy schedules.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.


04/14/03: Echinacacea & Quality Control; Obesity Update; Aortic Valve Stenosis, Arteriograms & Strokes; Preventing Recurrent Blood Clots

03/31/03: Breast Fibroadenomas & the Risk of Breast Cancer; Inflammatory Markers & Risk of Heart Failure; Update on Smallpox Vaccine; SARS Update

03/10/03: More Data on Hormone Replacement Therapy & the Risk of Breast Cancer; Oral Health & the Risk of Cardiovascular Disease; More Bad News about C-reactive Protein; Update: Daily Multivitamin & Minerals Supplements; Baby Aspirin & the Risk of Colorectal Adenomas; Aspirin & the Risk of Colorectal Polyps

03/03/03: Management of enlarging thyroid nodules; Long-term anticoagulation reduces the risk of recurrent blood clots in the veins; colon polyp recurrence after colonoscopic polyp removal; Vitamins C & E and Atherosclerotic Disease: The Debate Continues

02/24/03: Tamoxifen & Benign Breast Disease; New Recommendation on Digitalis Dosing; Creutzfeldt-Jakob Disease & the Nose; Radiologist Experience & Accuracy of Mammogram Interpretation; More Data on the Incidence of GI Side Effects with Selective COX-2 NSAIDs; Regular Rest Breaks & the Risk of Industrial Accidents

02/18/03: Update on Alzheimer's Disease; Very Low Birth-weight Babies & Cognitive Development; The Great Blood Pressure Medication Debate

02/03/03: Update on C-reactive Protein; COX-2 Inhibitors & Arterial Function; COX-2 Inhibitors and Gastrointestinal Complications; Telomere Shortening & Risk of Death

01/24/03: Bo-tox that BO Away!; The Super-sizing of America; Marijuana: A Gateway Drug?

01/21/03: Dietary Soy & Prostate Cancer Risks; Retention of Surgical Foreign Bodies after Surgery; Diet & hormone levels in adolescent girls

01/10/03: Can Aspirin Prevent Esophageal Cancer?; A Drink to Your Health!; Hormones & Breast Cancer; The Impact of Obesity on Lifespan

01/06/03:"The Pill" for Males?; Obesity & Diabetes Trends in the United States; Binge Drinking in the United States; One Less Reason to be Depressed; Liver Failure: Trends

12/20/02: Citrus Pectin & Cancer; Echinacea & the Common Cold; Update on High Blood Pressure Treatment

12/06/02: Calcium Intake & Prostate Cancer Risk; Alcohol Consumption & Risk of Breast Cancer; Reducing Blood Transfusions in Critically Ill Patients

12/06/02: Alcohol, Tamoxifen & Carotid Artery Wall Thickness; Coffee & Gallstones?; Irritable Bowel Syndrome Update; Statins: More Good News

11/22/02:Alcohol, HRT & the risk of breast cancer; hormone replacement therapy: more bad news; new vaccines may eliminate cervical cancer; more

11/15/02: The Effects of Diet & Exercise on Blood Pressure & Health; Growth Hormone & Sex Steroid Supplements & the Elderly; C-Reactive Protein & Cardiovascular Disease Risk

11/08/02: More Good News About Statin Drugs; Hormone replacement Therapy (HRT) & Alzheimer's Disease; A Role for Antibiotics in the Treatment of Vascular Disease?; more

11/01/02: Digoxin & gender; driving & degenerative disc disease; Coenzyme Q10 & Parkinson's Disease; Ginseng & erections; Viagra & stroke

10/25/02: Aspirin & coronary artery bypass surgery; glucosamine sulfate & progression of knee arthritis; hospital nurse staffing & patient mortality

10/18/02: Motor Vehicle Exhaust Pollution & Mortality; CT Scans, C-Reactive Protein & Heart Disease; Antiperspirant Use & the Risk of Breast Cancer; Atomic Bomb Radiation Exposure Update; more

10/04/02: Antioxidants & the Risk of Stomach Cancer; Best Way to Diagnose Appendicitis?; Coronary Artery Disease: Stent or Surgery?

09/27/02: Breast Feeding & the Risk of Asthma; HMOs & Quality of Care Scores; Red Wine & Vascular Disease

09/20/02: Dietary Folate & the Risk of Colorectal Cancer; Risks Associated with Smoking after Heart Attacks; BRCA1 Gene Mutation & the Risk of Breast & Non-breast Cancers; Breast Tissue Density & Inheritance

09/13/02: Dairy Products, Calcium, Vitamin D & the Risk of Breast Cancer; Efficacy of Nonprescription Smoking Cessation Aids; A Nutty Approach to Heart Disease Prevention; Update on Prostate Cancer

09/06/02: C-Reactive Protein & Estrogen Replacement Therapy; Walking Women & Cardiovascular Disease; Physical Activity Among Teenaged Girls

08/30/02: Babbling babies & brain function; homocysteine levels, vitamins & coronary artery disease; St. John's Wort & chemotherapy

08/16/02: A New Weapon Against Anthrax?; cataracts & motor vehicle accidents; gingko biloba takes a hit; air pollution & heart function during exercise; breast cancer genes & the estimated risk of breast cancer

08/09/02: Botulinum Toxin & Post-Stroke Spasticity; Intestinal Hormone Kills Appetite; Bone Marrow Cells Improve Blood Flow in Vascular Disease; Effectiveness of Restraining Orders on Domestic Violence

08/02/02: Mammography Saves Lives!; Obesity & the Risk of Heart Failure; High Sugar Diets & the Risk of Colon Cancer; Abuse During Childhood & Possible Effects of Genes on Antisocial Behaviors

07/26/02: Cancer: Nature vs. Nurture; Cardiorespiratory Fitness & Inflammation; Kidney Transplants from Cadaver Donors; Aircraft Cabin Air Recirculation & the Common Cold

07/19/02: PCBs & the Gender of Babies; Breastfeeding & the Risk of Breast Cancer; More Bad News About Hormone replacement Therapy

07/12/02: A cancer surgeon's perspective on hormone replacement therapy

07/08/02: Hormone replacement therapy & the risk of disease; more good news about statins; antioxidant vitamins & disease prevention; more

06/28/02: Antioxidants & the Risk of Alzheimer's Disease; Effects of Exercise on the Hearts of Patients with Mild Hypertension; Statins reduce cardiac events following angioplasty; more

06/21/02: Sex & violence and Advertising: Do Advertisers Get What they Pay For?; Don't Drink the Water (or the Salsa Either!); Vasectomy & Prostate Cancer Risk; Update on Smoking & Disease

06/14/02: Young Men, Obesity & Heart Disease; Breastfeeding & Obesity; Irritable Bowel Syndrome & rectal pain threshold; more data on cox-2 inhibitors & cancer; more

06/07/02: New coronary artery stent reduces risk of restenosis; possible cause of Parkinson's Disease identified; more

05/31/02: New biological insights into obesity & weight loss; broccoli kills cancer-causing stomach bug; anti-inflammatory drugs and the risk of heart attack

05/24/02: Molecular detection of tumor cells in the blood & prognosis; Cox-2 & breast/lung cancers; BRCA2 gene mutations & the risk of breast cancer; breast density & the risk of breast cancer

05/19/02: Moderate alcohol intake and blood sugar levels; more good news for tea drinkers; blood potassium levels & the risk of cardiovascular disease; ethnic differences in diabetic complications

05/10/02: Tea drinkers and the risk of death following heart attack; duration of breastfeeding & adult intelligence; abdominal aortic aneurysms: surgery or observation?

05/03/02: Risk of adverse drug reactions from newly released medications; preoperative beta-blockers may reduce heart bypass deaths; shape-shifting plastics may alter surgical practice; weight loss supplement may cause liver damage
04/26/02: Angry young men & risk of premature cardiovascular disease; stay-at-home dads & risk of cardiovascular disease; more on the effects of statins; dairy consumption and the risk of pre-diabetes; smallpox vaccine: good to the last drop?
04/19/02: Change your sex by drinking water?; Anti-inflammatory RXs may reduce growth of breast cancer cells; radiation treatment reduces repeat narrowing of bypass grafts
04/05/02: Fish & Omega-3 fatty acid consumption and cardiac health; news briefs
04/05/02: Can coffee reduce your risk of tooth decay?; exercise & blood pressure; a single high-fat meal reduces coronary artery function
04/01/02: Pre-diabetes: a newly defined category of health risk; teen television viewing and subsequent aggressive behavior; the benefits of strength training in the elderly; more ...
03/22/02: Bacteria, antibiotics & heart disease; mammograms: the debate continues; calcium & the risk of colon cancer ... and more
03/15/02: Mammography debate continues; statins & fracture risk; physical fitness & the risk of death; other intriguing findings
03/08/02: Blows to the chest & sudden cardiac death; air quality & the risk of lung cancer; tomatoes and your prostate
03/01/02: Diet & the risk of ovarian cancer; lifetime risk of developing high blood pressure; Osteoporosis prevention with a once-a-year injection?
02/26/02: The continuing controversy regarding screening mammography
02/22/02: Lowering body temperature after heart attack improves outcome; A silver lining for the chronically sleep-deprived?
02/15/02: Hormone replacement therapy & the risk of breast cancer; use it or lose it: Alzheimer's disease & cognitive stimulation; stress, divorce & death; child daycare, infections & parental guilt
02/08/02: Possible breakthrough in early cancer diagnosis; mammography: the controversy continues; CPR techniques revisited
02/01/02: Antibiotics in livestock feed & human disease; genetic detection of early colon cancer in the stool; genetic analysis of breast cancers may help decide treatment
01/25/02: Drug increases lifespan (if you're a fly...); workplace attitudes and smoking cessation; effects of inadequate sleep on surgeons
01/18/02: Lifelong effects of premature birth; smokers under the knife; aspirin and cardiovascular health
01/11/02: Estrogen levels in the blood & breast cancer risk; Heart attack: sex and survival; dangerous lettuce invaders
01/09/02: Cancer & aging: Two sides of the same coin?
01/04/02: Vitamin a & the risk of hip fracture in postmenopausal women; ovarian cancer risk and oral contraceptives
12/28/01: Magnetic Resonance Imaging (MRI) detects coronary artery disease; new development in obesity research; adverse childhood experiences & the risk of suicide attempts
12/21/01: Vaccination of children controls hepatitis a in the community; a possible cure for sickle cell disease; leptin and the risk of heart attacks
12/14/01: Chernobyl and the Risk of Thyroid Cancer in hildren; children & obesity; gastroesophageal reflux disease update
12/07/01: Update on school shootings; new implantable heart-assist device approved for further evaluation; prevention of fungal infections in pre-term babies
11/30/01: Flu vaccination in asthmatics; low-tar cigarettes are not less harmful; beans and your heart
11/21/01: Modified smallpox vaccine may reduce risk of cervical cancer; New approach to breast cancer diagnosis; New non-invasive prenatal diagnostic test for down's syndrome
11/16/01: Cholesterol-lowering drugs reduce risk of heart attack; supplemental radiation therapy reduces risk of breast cancer recurrence; brains of women may answer age-old questions
11/09/01: Bio-warfare (redux); my gray matter is bigger than yours; mad elk disease?
11/02/01: Making sense of bio-warfare
10/26/01: The impact of mammography on deaths due to breast cancer; diet & exercise may slow cancer cell growth; antidepressants and the risk of heart disease
10/19/01: New insights into autism; the wiley appendix
10/12/01: More bad news about obesity links to other diseases…Hey dad, can I borrow the car keys?
10/05/01: California leads nation in reduction of tobacco-related disease; exercise as an antidepressant?
09/25/01: Advances in the detection of breast cancer; primary care physician awareness of peripheral arterial disease; arsenic in the water
09/17/01: In perspective
09/12/01: Genes may hold secret to long life; men and women: cognitive function in the elderly; physical activity, obesity and the risk of pancreatic cancer
09/05/01: English milk cows prefer Beethoven and Simon & Garfunkel over Bananarama; new prostate cancer prevention study: looking for a few good men; exercise & diet can help prevent diabetes
08/28/01: Arthritis drugs may be linked with increased risk of heart disease; errors in blood clotting tests can be fatal; infant soy formula not associated with reproductive side effects

© 2002, Dr. Robert A. Wascher