C-reactive Protein & Stroke

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.

Bone Protection Following Discontinuation of Hormone Replacement Therapy

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.   

Body Weight & the Risk of Cancer

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. 

Dr. Robert A. Wascher