Nephrology

Intensive blood pressure control doesn’t slow the progression of chronic kidney disease any better than standard blood pressure control in most patients, according to a report in the Sept. 2 New England Journal of Medicine.

It appears that the more intensive approach may benefit only patients who have proteinuria with a protein:creatinine ratio greater than 0.22, a value that is compatible with the widely accepted threshold of 300 mg/day for absolute urinary protein excretion, said Dr. Lawrence J. Appel of Johns Hopkins University, Baltimore, and his associates in the AASK (African-American Study of Kidney Disease and Hypertension) Collaborative Research Group.

Until now, “few trials have tested the effects of intensive blood pressure control [compared with conventional control] on the progression of chronic kidney disease, and the findings from such trials have been inconsistent. Despite a lack of compelling evidence, numerous guidelines recommend a reduced blood pressure target in patients with CKD,” they wrote.

Previous studies have rarely followed patients beyond 5 years, even though it typically takes longer than that for end-stage renal disease (ESRD) to develop in patients with CKD.

The AASK study compared outcomes between the two approaches to BP control in 1,094 black adults with mild to moderate hypertensive chronic kidney disease (defined as diastolic BP greater than 95 mm Hg and a glomerular filtration rate of 20-65 mL/min) but without marked proteinuria. Patients with diabetes were excluded from the trial.

In the first phase of the AASK investigation, patients were randomly assigned to either intensive BP control with a target of 92 mm Hg or lower mean arterial pressure (that is, lower than the usual target of 130/80 mm Hg recommended for CKD patients) or to conventional BP control with a target of 102-107 mm Hg mean arterial pressure (which corresponds to the conventional BP target of 140/90 mm Hg).

Throughout this initial phase of the trial, which lasted approximately 4 years, mean blood pressure was significantly lower in the intensive-control group (130/78 mm Hg) than in the standard-control group (141/86 mm Hg), yet there was no significant difference in the primary outcome of progression of kidney disease, development of ESRD, or death. Likewise, there was no significant difference between the two approaches in secondary or clinical outcomes.

In the second phase of the AASK investigation, patients who had not yet developed ESRD were invited to continue in a cohort portion of the trial, in which the BP target was 140/90 mm Hg. In 2004, when national guidelines were changed, this target was amended to lower than 130/80 mm Hg.

After a cumulative follow-up of 8-12 years, there still was no significant difference in primary or secondary outcomes between those who were initially assigned to the intensive-control and the standard-control groups. More intensive BP control did not slow the rate of progression of CKD, Dr. Appel and his associates reported (N. Engl. J. Med. 2010;363:918-29).

However, the intensive-control approach did benefit one subgroup of patients with proteinuria: those who had a protein:creatinine ratio of more than 0.22 at baseline. These patients showed a significant reduction in the primary outcome of progression of kidney disease, development of ESRD, or death, as well as in secondary and clinical outcomes.

The reason for this discrepancy is not known. “Overall, it is hard to develop a coherent, biologically plausible argument for a qualitative interaction between harm in patients without proteinuria and benefit in those with proteinuria,” the researchers said.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the Office of Research in Minority Health, and the National Institutes of Health. King Pharmaceuticals provided financial support and donated antihypertensive medications to each clinical center. Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn also donated antihypertensive drugs. None of these companies had any role in the design of the study, the accrual or analysis of data, or the preparation of the manuscript. Some of the investigators reported being in consultant and/or advisory board roles or receiving funds from numerous companies including Daiichi-Sankyo, Novartis, Amgen, King Pharmaceuticals, Abbott, Boehringer-Ingelheim, Litholink, Eli Lilly, Takeda, Merck, and Watson. Dr. Ingelfinger reported having no conflicts of interest.

Intensive blood pressure control doesn’t slow the progression of chronic kidney disease any better than standard blood pressure control in most patients, according to a report in the Sept. 2 New England Journal of Medicine.

It appears that the more intensive approach may benefit only patients who have proteinuria with a protein:creatinine ratio greater than 0.22, a value that is compatible with the widely accepted threshold of 300 mg/day for absolute urinary protein excretion, said Dr. Lawrence J. Appel of Johns Hopkins University, Baltimore, and his associates in the AASK (African-American Study of Kidney Disease and Hypertension) Collaborative Research Group.

Until now, “few trials have tested the effects of intensive blood pressure control [compared with conventional control] on the progression of chronic kidney disease, and the findings from such trials have been inconsistent. Despite a lack of compelling evidence, numerous guidelines recommend a reduced blood pressure target in patients with CKD,” they wrote.

Previous studies have rarely followed patients beyond 5 years, even though it typically takes longer than that for end-stage renal disease (ESRD) to develop in patients with CKD.

The AASK study compared outcomes between the two approaches to BP control in 1,094 black adults with mild to moderate hypertensive chronic kidney disease (defined as diastolic BP greater than 95 mm Hg and a glomerular filtration rate of 20-65 mL/min) but without marked proteinuria. Patients with diabetes were excluded from the trial.

In the first phase of the AASK investigation, patients were randomly assigned to either intensive BP control with a target of 92 mm Hg or lower mean arterial pressure (that is, lower than the usual target of 130/80 mm Hg recommended for CKD patients) or to conventional BP control with a target of 102-107 mm Hg mean arterial pressure (which corresponds to the conventional BP target of 140/90 mm Hg).

Throughout this initial phase of the trial, which lasted approximately 4 years, mean blood pressure was significantly lower in the intensive-control group (130/78 mm Hg) than in the standard-control group (141/86 mm Hg), yet there was no significant difference in the primary outcome of progression of kidney disease, development of ESRD, or death. Likewise, there was no significant difference between the two approaches in secondary or clinical outcomes.

In the second phase of the AASK investigation, patients who had not yet developed ESRD were invited to continue in a cohort portion of the trial, in which the BP target was 140/90 mm Hg. In 2004, when national guidelines were changed, this target was amended to lower than 130/80 mm Hg.

After a cumulative follow-up of 8-12 years, there still was no significant difference in primary or secondary outcomes between those who were initially assigned to the intensive-control and the standard-control groups. More intensive BP control did not slow the rate of progression of CKD, Dr. Appel and his associates reported (N. Engl. J. Med. 2010;363:918-29).

However, the intensive-control approach did benefit one subgroup of patients with proteinuria: those who had a protein:creatinine ratio of more than 0.22 at baseline. These patients showed a significant reduction in the primary outcome of progression of kidney disease, development of ESRD, or death, as well as in secondary and clinical outcomes.

The reason for this discrepancy is not known. “Overall, it is hard to develop a coherent, biologically plausible argument for a qualitative interaction between harm in patients without proteinuria and benefit in those with proteinuria,” the researchers said.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the Office of Research in Minority Health, and the National Institutes of Health. King Pharmaceuticals provided financial support and donated antihypertensive medications to each clinical center. Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn also donated antihypertensive drugs. None of these companies had any role in the design of the study, the accrual or analysis of data, or the preparation of the manuscript. Some of the investigators reported being in consultant and/or advisory board roles or receiving funds from numerous companies including Daiichi-Sankyo, Novartis, Amgen, King Pharmaceuticals, Abbott, Boehringer-Ingelheim, Litholink, Eli Lilly, Takeda, Merck, and Watson. Dr. Ingelfinger reported having no conflicts of interest.

Intensive blood pressure control doesn’t slow the progression of chronic kidney disease any better than standard blood pressure control in most patients, according to a report in the Sept. 2 New England Journal of Medicine.

It appears that the more intensive approach may benefit only patients who have proteinuria with a protein:creatinine ratio greater than 0.22, a value that is compatible with the widely accepted threshold of 300 mg/day for absolute urinary protein excretion, said Dr. Lawrence J. Appel of Johns Hopkins University, Baltimore, and his associates in the AASK (African-American Study of Kidney Disease and Hypertension) Collaborative Research Group.

Until now, “few trials have tested the effects of intensive blood pressure control [compared with conventional control] on the progression of chronic kidney disease, and the findings from such trials have been inconsistent. Despite a lack of compelling evidence, numerous guidelines recommend a reduced blood pressure target in patients with CKD,” they wrote.

Previous studies have rarely followed patients beyond 5 years, even though it typically takes longer than that for end-stage renal disease (ESRD) to develop in patients with CKD.

The AASK study compared outcomes between the two approaches to BP control in 1,094 black adults with mild to moderate hypertensive chronic kidney disease (defined as diastolic BP greater than 95 mm Hg and a glomerular filtration rate of 20-65 mL/min) but without marked proteinuria. Patients with diabetes were excluded from the trial.

In the first phase of the AASK investigation, patients were randomly assigned to either intensive BP control with a target of 92 mm Hg or lower mean arterial pressure (that is, lower than the usual target of 130/80 mm Hg recommended for CKD patients) or to conventional BP control with a target of 102-107 mm Hg mean arterial pressure (which corresponds to the conventional BP target of 140/90 mm Hg).

Throughout this initial phase of the trial, which lasted approximately 4 years, mean blood pressure was significantly lower in the intensive-control group (130/78 mm Hg) than in the standard-control group (141/86 mm Hg), yet there was no significant difference in the primary outcome of progression of kidney disease, development of ESRD, or death. Likewise, there was no significant difference between the two approaches in secondary or clinical outcomes.

In the second phase of the AASK investigation, patients who had not yet developed ESRD were invited to continue in a cohort portion of the trial, in which the BP target was 140/90 mm Hg. In 2004, when national guidelines were changed, this target was amended to lower than 130/80 mm Hg.

After a cumulative follow-up of 8-12 years, there still was no significant difference in primary or secondary outcomes between those who were initially assigned to the intensive-control and the standard-control groups. More intensive BP control did not slow the rate of progression of CKD, Dr. Appel and his associates reported (N. Engl. J. Med. 2010;363:918-29).

However, the intensive-control approach did benefit one subgroup of patients with proteinuria: those who had a protein:creatinine ratio of more than 0.22 at baseline. These patients showed a significant reduction in the primary outcome of progression of kidney disease, development of ESRD, or death, as well as in secondary and clinical outcomes.

The reason for this discrepancy is not known. “Overall, it is hard to develop a coherent, biologically plausible argument for a qualitative interaction between harm in patients without proteinuria and benefit in those with proteinuria,” the researchers said.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the Office of Research in Minority Health, and the National Institutes of Health. King Pharmaceuticals provided financial support and donated antihypertensive medications to each clinical center. Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn also donated antihypertensive drugs. None of these companies had any role in the design of the study, the accrual or analysis of data, or the preparation of the manuscript. Some of the investigators reported being in consultant and/or advisory board roles or receiving funds from numerous companies including Daiichi-Sankyo, Novartis, Amgen, King Pharmaceuticals, Abbott, Boehringer-Ingelheim, Litholink, Eli Lilly, Takeda, Merck, and Watson. Dr. Ingelfinger reported having no conflicts of interest.

Patients newly diagnosed with prostate cancer who have a prostate specific antigen levels of 4.0 ng/mL or below tend to receive aggressive therapy despite having a low risk of disease, according to a retrospective study of 123,934 men in the July 26 issue of the Archives of Internal Medicine.

In a multivariate analysis correcting for age, race, and year of diagnosis, men with screen-detected prostate cancer and prostate specific antigen (PSA) values of 4.0 ng/mL or below were 49% more likely to undergo radical prostatectomy and 39% more likely to undergo radiation therapy than were men with non–screen detected prostate cancer, according to Yu-Hsuan Shao, Ph.D., of the Cancer Institute of New Jersey, New Brunswick, and her colleagues.

Although 54% of men diagnosed with prostate cancer with low PSA levels harbor low-risk disease, 77% of them underwent radical prostatectomy or radiotherapy. Men with low PSA levels and screen-detected prostate cancer were 33% less likely to have high-grade disease than were men with non–screen detected prostate cancer, the investigators said.

“The finding that men in low-risk groups were treated intensively raises the concern of overtreatment, especially among older patients,” the authors wrote.

Investigators used the Surveillance, Epidemiology, and End Results (SEER) database, covering approximately 26% of the U.S. population, to identify men newly diagnosed with prostate cancer between 2004 and 2006. They excluded men under the age of 24 years, those with missing PSA values, or those with missing Gleason scores and clinical stage.

The men in the study were divided into four groups based on PSA values. A total of 14% of the men had PSA values of 4.0 ng/mL or less, 57.6% had values between 4.1-10.0 ng/mL, 15.9% had values between 10.1-20.0 ng/mL, and 12.5% had values above 20 ng/mL (Arch. Int. Med. 2010;170:1256-61).

Of the men with the lowest PSA values, 44% underwent radical prostatectomy, 33% underwent radiation therapy, and 23% were treated with conservative management. In contrast, of the men with the highest PSA levels, 12.5% underwent radical prostatectomy, 31.5% underwent radiation therapy, and 56% were treated with conservative management.

One of the study’s authors acknowledged receiving clinical research funding from the Ohl Foundation, the New Jersey Commission on Cancer Research, and the Agency for Healthcare Research and Quality. Another author acknowledged receiving clinical research funding from Sanofi-Aventis and consultation fees from Blue Cross/Blue Shield. The study was supported by the National Cancer Institute, the Cancer Institute of New Jersey, and the Robert Wood Johnson Foundation.

Patients newly diagnosed with prostate cancer who have a prostate specific antigen levels of 4.0 ng/mL or below tend to receive aggressive therapy despite having a low risk of disease, according to a retrospective study of 123,934 men in the July 26 issue of the Archives of Internal Medicine.

In a multivariate analysis correcting for age, race, and year of diagnosis, men with screen-detected prostate cancer and prostate specific antigen (PSA) values of 4.0 ng/mL or below were 49% more likely to undergo radical prostatectomy and 39% more likely to undergo radiation therapy than were men with non–screen detected prostate cancer, according to Yu-Hsuan Shao, Ph.D., of the Cancer Institute of New Jersey, New Brunswick, and her colleagues.

Although 54% of men diagnosed with prostate cancer with low PSA levels harbor low-risk disease, 77% of them underwent radical prostatectomy or radiotherapy. Men with low PSA levels and screen-detected prostate cancer were 33% less likely to have high-grade disease than were men with non–screen detected prostate cancer, the investigators said.

“The finding that men in low-risk groups were treated intensively raises the concern of overtreatment, especially among older patients,” the authors wrote.

Investigators used the Surveillance, Epidemiology, and End Results (SEER) database, covering approximately 26% of the U.S. population, to identify men newly diagnosed with prostate cancer between 2004 and 2006. They excluded men under the age of 24 years, those with missing PSA values, or those with missing Gleason scores and clinical stage.

The men in the study were divided into four groups based on PSA values. A total of 14% of the men had PSA values of 4.0 ng/mL or less, 57.6% had values between 4.1-10.0 ng/mL, 15.9% had values between 10.1-20.0 ng/mL, and 12.5% had values above 20 ng/mL (Arch. Int. Med. 2010;170:1256-61).

Of the men with the lowest PSA values, 44% underwent radical prostatectomy, 33% underwent radiation therapy, and 23% were treated with conservative management. In contrast, of the men with the highest PSA levels, 12.5% underwent radical prostatectomy, 31.5% underwent radiation therapy, and 56% were treated with conservative management.

One of the study’s authors acknowledged receiving clinical research funding from the Ohl Foundation, the New Jersey Commission on Cancer Research, and the Agency for Healthcare Research and Quality. Another author acknowledged receiving clinical research funding from Sanofi-Aventis and consultation fees from Blue Cross/Blue Shield. The study was supported by the National Cancer Institute, the Cancer Institute of New Jersey, and the Robert Wood Johnson Foundation.

Patients newly diagnosed with prostate cancer who have a prostate specific antigen levels of 4.0 ng/mL or below tend to receive aggressive therapy despite having a low risk of disease, according to a retrospective study of 123,934 men in the July 26 issue of the Archives of Internal Medicine.

In a multivariate analysis correcting for age, race, and year of diagnosis, men with screen-detected prostate cancer and prostate specific antigen (PSA) values of 4.0 ng/mL or below were 49% more likely to undergo radical prostatectomy and 39% more likely to undergo radiation therapy than were men with non–screen detected prostate cancer, according to Yu-Hsuan Shao, Ph.D., of the Cancer Institute of New Jersey, New Brunswick, and her colleagues.

Although 54% of men diagnosed with prostate cancer with low PSA levels harbor low-risk disease, 77% of them underwent radical prostatectomy or radiotherapy. Men with low PSA levels and screen-detected prostate cancer were 33% less likely to have high-grade disease than were men with non–screen detected prostate cancer, the investigators said.

“The finding that men in low-risk groups were treated intensively raises the concern of overtreatment, especially among older patients,” the authors wrote.

Investigators used the Surveillance, Epidemiology, and End Results (SEER) database, covering approximately 26% of the U.S. population, to identify men newly diagnosed with prostate cancer between 2004 and 2006. They excluded men under the age of 24 years, those with missing PSA values, or those with missing Gleason scores and clinical stage.

The men in the study were divided into four groups based on PSA values. A total of 14% of the men had PSA values of 4.0 ng/mL or less, 57.6% had values between 4.1-10.0 ng/mL, 15.9% had values between 10.1-20.0 ng/mL, and 12.5% had values above 20 ng/mL (Arch. Int. Med. 2010;170:1256-61).

Of the men with the lowest PSA values, 44% underwent radical prostatectomy, 33% underwent radiation therapy, and 23% were treated with conservative management. In contrast, of the men with the highest PSA levels, 12.5% underwent radical prostatectomy, 31.5% underwent radiation therapy, and 56% were treated with conservative management.

One of the study’s authors acknowledged receiving clinical research funding from the Ohl Foundation, the New Jersey Commission on Cancer Research, and the Agency for Healthcare Research and Quality. Another author acknowledged receiving clinical research funding from Sanofi-Aventis and consultation fees from Blue Cross/Blue Shield. The study was supported by the National Cancer Institute, the Cancer Institute of New Jersey, and the Robert Wood Johnson Foundation.

Dietary calcium was associated with significantly increased risk of prostate cancer in Chinese men with a below-average body mass index, according to an analysis of a large data set.

Researchers found that among subjects with a BMI below the median 22.9 kg/m

Data from previous studies have suggested a link between calcium and prostate cancer, but these studies have not been able to separate dairy products from calcium, said Lesley M. Butler, Ph.D., of Colorado State University in Fort Collins, and colleagues.

To more accurately assess the link between dietary calcium and prostate cancer, the researchers focused on a population of Chinese men whose dairy intake was relatively low. In general, Asian diets contain few dairy products, compared with Western diets, the researchers noted. Instead, most of the calcium in Asian diets comes from nondairy sources such as broccoli, kale, bok choy, and soy products. The researchers reviewed data from the Singapore Chinese Health Study, focusing on 27,293 men who did not have cancer when they entered the study between April 1993 and December 1998 (Cancer Res. 2010 June 1 [doi:10.1158/0008-5472.CAN-09-4544]).

Overall, dietary calcium was associated with a nonsignificant 25% increase in prostate cancer risk for the highest quartile of calcium intake (median of 659 mg/day) vs. the lowest quartile (median of 211 mg/day).

The study participants completed a 165-item food frequency questionnaire to assess their diets over the past year. Baseline characteristics including age, education, physical activity, and BMI were similar among the four quartiles.

Overall, the median daily intake of dairy products in the study population was 19.3 g. The greatest contributions of different food sources to daily calcium intake were vegetables (19.3%), dairy (17.3%), grain products (14.7%), soy products (11.8%), fruit (7.3%), and fish (6.2%). The variety of food sources suggest that the link between prostate cancer risk and calcium intake is not likely to be related to any particular food group, the researchers noted.

Neither age nor physical activity had an effect on the association between calcium and cancer, the researchers wrote.

“Our study is the first to report a positive association between calcium and prostate cancer risk at such a low calcium level,” the researchers said. Previous studies have shown that calcium is absorbed more efficiently in the Chinese population, compared with the white population, and among thinner people compared with heavier people, which is why a study of relatively thin Chinese men might be more likely to reveal a cancer/calcium connection than a study of heavier white men, the researchers wrote.

The study was limited by an inability to assess any variation of the calcium/cancer connection based on stage of disease, and more research is needed to evaluate the role of calcium in prostate cancer, compared with other components of dairy products, they added.

Disclosures: The study was supported by a grant from the National Cancer Institute. Dr. Butler reported having no financial conflicts.

My Take

Over 1,000 mg May Be Too Much

Previous studies indicated that high intakes of calcium (more than 1,000–1,500 mg/day) may increase prostate cancer risk. As there is no established benefit for men at such high intakes, it makes sense for men to not go much beyond the 1,000-mg/day range until further studies have been done. However, intakes of calcium that are too low (less than 700 mg/day) may increase risk of some conditions, such as hypertension and colorectal cancer. Thus, it is reasonable for men to be in the range of 700–1,000 mg/day, but prudent not to go too much lower.

These results need to be confirmed in other studies where calcium intake is relatively low and there are not many dairy products. Also, since many men take calcium supplements, that might be an informative group to study. Finally, men with prostate cancer need to be studied, as the results would be most pertinent to them.

In addition, the authors theorize that leaner men may absorb calcium better. The evidence for this is limited at this time. This could be a chance finding, so it also needs to be replicated in other populations.

EDWARD GIOVANNUCCI, M.D., is a professor of epidemiology and nutrition at Harvard University, Cambridge, Mass.

Dietary calcium was associated with significantly increased risk of prostate cancer in Chinese men with a below-average body mass index, according to an analysis of a large data set.

Researchers found that among subjects with a BMI below the median 22.9 kg/m

Data from previous studies have suggested a link between calcium and prostate cancer, but these studies have not been able to separate dairy products from calcium, said Lesley M. Butler, Ph.D., of Colorado State University in Fort Collins, and colleagues.

To more accurately assess the link between dietary calcium and prostate cancer, the researchers focused on a population of Chinese men whose dairy intake was relatively low. In general, Asian diets contain few dairy products, compared with Western diets, the researchers noted. Instead, most of the calcium in Asian diets comes from nondairy sources such as broccoli, kale, bok choy, and soy products. The researchers reviewed data from the Singapore Chinese Health Study, focusing on 27,293 men who did not have cancer when they entered the study between April 1993 and December 1998 (Cancer Res. 2010 June 1 [doi:10.1158/0008-5472.CAN-09-4544]).

Overall, dietary calcium was associated with a nonsignificant 25% increase in prostate cancer risk for the highest quartile of calcium intake (median of 659 mg/day) vs. the lowest quartile (median of 211 mg/day).

The study participants completed a 165-item food frequency questionnaire to assess their diets over the past year. Baseline characteristics including age, education, physical activity, and BMI were similar among the four quartiles.

Overall, the median daily intake of dairy products in the study population was 19.3 g. The greatest contributions of different food sources to daily calcium intake were vegetables (19.3%), dairy (17.3%), grain products (14.7%), soy products (11.8%), fruit (7.3%), and fish (6.2%). The variety of food sources suggest that the link between prostate cancer risk and calcium intake is not likely to be related to any particular food group, the researchers noted.

Neither age nor physical activity had an effect on the association between calcium and cancer, the researchers wrote.

“Our study is the first to report a positive association between calcium and prostate cancer risk at such a low calcium level,” the researchers said. Previous studies have shown that calcium is absorbed more efficiently in the Chinese population, compared with the white population, and among thinner people compared with heavier people, which is why a study of relatively thin Chinese men might be more likely to reveal a cancer/calcium connection than a study of heavier white men, the researchers wrote.

The study was limited by an inability to assess any variation of the calcium/cancer connection based on stage of disease, and more research is needed to evaluate the role of calcium in prostate cancer, compared with other components of dairy products, they added.

Disclosures: The study was supported by a grant from the National Cancer Institute. Dr. Butler reported having no financial conflicts.

My Take

Over 1,000 mg May Be Too Much

Previous studies indicated that high intakes of calcium (more than 1,000–1,500 mg/day) may increase prostate cancer risk. As there is no established benefit for men at such high intakes, it makes sense for men to not go much beyond the 1,000-mg/day range until further studies have been done. However, intakes of calcium that are too low (less than 700 mg/day) may increase risk of some conditions, such as hypertension and colorectal cancer. Thus, it is reasonable for men to be in the range of 700–1,000 mg/day, but prudent not to go too much lower.

These results need to be confirmed in other studies where calcium intake is relatively low and there are not many dairy products. Also, since many men take calcium supplements, that might be an informative group to study. Finally, men with prostate cancer need to be studied, as the results would be most pertinent to them.

In addition, the authors theorize that leaner men may absorb calcium better. The evidence for this is limited at this time. This could be a chance finding, so it also needs to be replicated in other populations.

EDWARD GIOVANNUCCI, M.D., is a professor of epidemiology and nutrition at Harvard University, Cambridge, Mass.

Dietary calcium was associated with significantly increased risk of prostate cancer in Chinese men with a below-average body mass index, according to an analysis of a large data set.

Researchers found that among subjects with a BMI below the median 22.9 kg/m

Data from previous studies have suggested a link between calcium and prostate cancer, but these studies have not been able to separate dairy products from calcium, said Lesley M. Butler, Ph.D., of Colorado State University in Fort Collins, and colleagues.

To more accurately assess the link between dietary calcium and prostate cancer, the researchers focused on a population of Chinese men whose dairy intake was relatively low. In general, Asian diets contain few dairy products, compared with Western diets, the researchers noted. Instead, most of the calcium in Asian diets comes from nondairy sources such as broccoli, kale, bok choy, and soy products. The researchers reviewed data from the Singapore Chinese Health Study, focusing on 27,293 men who did not have cancer when they entered the study between April 1993 and December 1998 (Cancer Res. 2010 June 1 [doi:10.1158/0008-5472.CAN-09-4544]).

Overall, dietary calcium was associated with a nonsignificant 25% increase in prostate cancer risk for the highest quartile of calcium intake (median of 659 mg/day) vs. the lowest quartile (median of 211 mg/day).

The study participants completed a 165-item food frequency questionnaire to assess their diets over the past year. Baseline characteristics including age, education, physical activity, and BMI were similar among the four quartiles.

Overall, the median daily intake of dairy products in the study population was 19.3 g. The greatest contributions of different food sources to daily calcium intake were vegetables (19.3%), dairy (17.3%), grain products (14.7%), soy products (11.8%), fruit (7.3%), and fish (6.2%). The variety of food sources suggest that the link between prostate cancer risk and calcium intake is not likely to be related to any particular food group, the researchers noted.

Neither age nor physical activity had an effect on the association between calcium and cancer, the researchers wrote.

“Our study is the first to report a positive association between calcium and prostate cancer risk at such a low calcium level,” the researchers said. Previous studies have shown that calcium is absorbed more efficiently in the Chinese population, compared with the white population, and among thinner people compared with heavier people, which is why a study of relatively thin Chinese men might be more likely to reveal a cancer/calcium connection than a study of heavier white men, the researchers wrote.

The study was limited by an inability to assess any variation of the calcium/cancer connection based on stage of disease, and more research is needed to evaluate the role of calcium in prostate cancer, compared with other components of dairy products, they added.

Disclosures: The study was supported by a grant from the National Cancer Institute. Dr. Butler reported having no financial conflicts.

My Take

Over 1,000 mg May Be Too Much

Previous studies indicated that high intakes of calcium (more than 1,000–1,500 mg/day) may increase prostate cancer risk. As there is no established benefit for men at such high intakes, it makes sense for men to not go much beyond the 1,000-mg/day range until further studies have been done. However, intakes of calcium that are too low (less than 700 mg/day) may increase risk of some conditions, such as hypertension and colorectal cancer. Thus, it is reasonable for men to be in the range of 700–1,000 mg/day, but prudent not to go too much lower.

These results need to be confirmed in other studies where calcium intake is relatively low and there are not many dairy products. Also, since many men take calcium supplements, that might be an informative group to study. Finally, men with prostate cancer need to be studied, as the results would be most pertinent to them.

In addition, the authors theorize that leaner men may absorb calcium better. The evidence for this is limited at this time. This could be a chance finding, so it also needs to be replicated in other populations.

EDWARD GIOVANNUCCI, M.D., is a professor of epidemiology and nutrition at Harvard University, Cambridge, Mass.

Major Finding: Exercise equivalent to 30 minutes of brisk walking per day, 4 days per week, is associated with a 65% decrease in the risk of sexual dysfunction.

Data Source: Study of 178 healthy men.

Disclosures: Dr. McNamara reported that she had no conflicts of interest. The study was supported by the Department of Defense and the Department of Veterans Affairs.

SAN FRANCISCO — Higher levels of exercise are associated with lower levels of sexual dysfunction, according to a study of 178 healthy men.

Men who reported exercise of at least 9 metabolic equivalents (METs) per week were 65% less likely to report sexual dysfunction. Brisk walking for 30 minutes a day for 4 days per week is equivalent to about 9 METs, according to Dr. Erin R. McNamara of Duke University Medical Center, Durham, N.C., who presented the results of her study at the meeting.

“If men won't exercise for the cardiovascular benefits, maybe they'll exercise to have better sex,” Dr. McNamara said at a news briefing.

The men in the study were all enrolled in a prospective case-control study at the Durham Veterans Affairs Medical Center. Their mean age was 62 years, and their mean body mass index was 30.7 kg/m

The sexual function survey consisted of six questions, asking men to evaluate their ability to have an erection, the quality and frequency of their erections, their ability to reach orgasm, their overall sexual ability, and the extent to which they were bothered by their sexual functioning. The investigators converted scores on the survey to a 0–100 scale. Overall, the participants' mean sexual function score was 53.

The men also were asked to assess their duration, intensity, and frequency of exercise. The investigators converted these estimates to MET hours per week. They classified men reporting fewer than 3 MET hours per week as sedentary (53% of the sample), 3–8 MET hours as active (14% of the sample), 9–17 MET hours as moderately active (9% of the sample), and 18 or more MET hours as highly active (24% of the sample).

Mean sexual function scores were 42 for sedentary men, 50 for active men, 72 for moderately active men, and 70 for highly active men. The trend was statistically significant.

In a multivariate analysis, the investigators controlled for age, race, BMI, heart disease, diabetes, medications, and depression. They defined a sexual function score of less than 40 as sexual dysfunction. Compared with sedentary men, those reporting moderate or high levels of physical activity were 65% less likely to have sexual dysfunction.

In an interview, Dr. McNamara emphasized that her study demonstrated only correlation, not causation. Asked to speculate on the reason for the association, she said, “Just as exercise provides cardiovascular benefit by increasing blood flow, we think the same thing probably happens [with sexual function] because the penis is engorged with blood vessels.” She also suggested that exercise may improve sexual function as a psychological byproduct of improved feelings of well-being.

Men with moderate or high levels of physical activity were 65% less likely to have sexual dysfunction.

Source Courtesy Ken Trombatore

Major Finding: Exercise equivalent to 30 minutes of brisk walking per day, 4 days per week, is associated with a 65% decrease in the risk of sexual dysfunction.

Data Source: Study of 178 healthy men.

Disclosures: Dr. McNamara reported that she had no conflicts of interest. The study was supported by the Department of Defense and the Department of Veterans Affairs.

SAN FRANCISCO — Higher levels of exercise are associated with lower levels of sexual dysfunction, according to a study of 178 healthy men.

Men who reported exercise of at least 9 metabolic equivalents (METs) per week were 65% less likely to report sexual dysfunction. Brisk walking for 30 minutes a day for 4 days per week is equivalent to about 9 METs, according to Dr. Erin R. McNamara of Duke University Medical Center, Durham, N.C., who presented the results of her study at the meeting.

“If men won't exercise for the cardiovascular benefits, maybe they'll exercise to have better sex,” Dr. McNamara said at a news briefing.

The men in the study were all enrolled in a prospective case-control study at the Durham Veterans Affairs Medical Center. Their mean age was 62 years, and their mean body mass index was 30.7 kg/m

The sexual function survey consisted of six questions, asking men to evaluate their ability to have an erection, the quality and frequency of their erections, their ability to reach orgasm, their overall sexual ability, and the extent to which they were bothered by their sexual functioning. The investigators converted scores on the survey to a 0–100 scale. Overall, the participants' mean sexual function score was 53.

The men also were asked to assess their duration, intensity, and frequency of exercise. The investigators converted these estimates to MET hours per week. They classified men reporting fewer than 3 MET hours per week as sedentary (53% of the sample), 3–8 MET hours as active (14% of the sample), 9–17 MET hours as moderately active (9% of the sample), and 18 or more MET hours as highly active (24% of the sample).

Mean sexual function scores were 42 for sedentary men, 50 for active men, 72 for moderately active men, and 70 for highly active men. The trend was statistically significant.

In a multivariate analysis, the investigators controlled for age, race, BMI, heart disease, diabetes, medications, and depression. They defined a sexual function score of less than 40 as sexual dysfunction. Compared with sedentary men, those reporting moderate or high levels of physical activity were 65% less likely to have sexual dysfunction.

In an interview, Dr. McNamara emphasized that her study demonstrated only correlation, not causation. Asked to speculate on the reason for the association, she said, “Just as exercise provides cardiovascular benefit by increasing blood flow, we think the same thing probably happens [with sexual function] because the penis is engorged with blood vessels.” She also suggested that exercise may improve sexual function as a psychological byproduct of improved feelings of well-being.

Men with moderate or high levels of physical activity were 65% less likely to have sexual dysfunction.

Source Courtesy Ken Trombatore

Major Finding: Exercise equivalent to 30 minutes of brisk walking per day, 4 days per week, is associated with a 65% decrease in the risk of sexual dysfunction.

Data Source: Study of 178 healthy men.

Disclosures: Dr. McNamara reported that she had no conflicts of interest. The study was supported by the Department of Defense and the Department of Veterans Affairs.

SAN FRANCISCO — Higher levels of exercise are associated with lower levels of sexual dysfunction, according to a study of 178 healthy men.

Men who reported exercise of at least 9 metabolic equivalents (METs) per week were 65% less likely to report sexual dysfunction. Brisk walking for 30 minutes a day for 4 days per week is equivalent to about 9 METs, according to Dr. Erin R. McNamara of Duke University Medical Center, Durham, N.C., who presented the results of her study at the meeting.

“If men won't exercise for the cardiovascular benefits, maybe they'll exercise to have better sex,” Dr. McNamara said at a news briefing.

The men in the study were all enrolled in a prospective case-control study at the Durham Veterans Affairs Medical Center. Their mean age was 62 years, and their mean body mass index was 30.7 kg/m

The sexual function survey consisted of six questions, asking men to evaluate their ability to have an erection, the quality and frequency of their erections, their ability to reach orgasm, their overall sexual ability, and the extent to which they were bothered by their sexual functioning. The investigators converted scores on the survey to a 0–100 scale. Overall, the participants' mean sexual function score was 53.

The men also were asked to assess their duration, intensity, and frequency of exercise. The investigators converted these estimates to MET hours per week. They classified men reporting fewer than 3 MET hours per week as sedentary (53% of the sample), 3–8 MET hours as active (14% of the sample), 9–17 MET hours as moderately active (9% of the sample), and 18 or more MET hours as highly active (24% of the sample).

Mean sexual function scores were 42 for sedentary men, 50 for active men, 72 for moderately active men, and 70 for highly active men. The trend was statistically significant.

In a multivariate analysis, the investigators controlled for age, race, BMI, heart disease, diabetes, medications, and depression. They defined a sexual function score of less than 40 as sexual dysfunction. Compared with sedentary men, those reporting moderate or high levels of physical activity were 65% less likely to have sexual dysfunction.

In an interview, Dr. McNamara emphasized that her study demonstrated only correlation, not causation. Asked to speculate on the reason for the association, she said, “Just as exercise provides cardiovascular benefit by increasing blood flow, we think the same thing probably happens [with sexual function] because the penis is engorged with blood vessels.” She also suggested that exercise may improve sexual function as a psychological byproduct of improved feelings of well-being.

Men with moderate or high levels of physical activity were 65% less likely to have sexual dysfunction.

Source Courtesy Ken Trombatore

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men on active surveillance for prostate cancer may be overtreated if clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw said at a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

“For patients managed on active surveillance, this raises what we believe is a cautionary tale that strict follow-up with the definitions of either linear regression, threshold, or velocities may lead to a false rate of treatment for patients on surveillance who don't need it,” said Dr. Loblaw, a radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

Research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer, he said. This surveillance typically entails PSA monitoring, with initiatation of treatment often based on a PSA trigger.

The researchers tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of disease progression after a median follow-up of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%), first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%), linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%), overall PSA velocity of greater than 2 ng/mL per year (42%), and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a PSA threshold of 20 ng/mL has a low false trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, Dr. Loblaw said.

To assess PSA changes, he said, clinicians at his center have started using and are validating a general linear mixed model that is freely available online (www.asure.ca

“It allows us to smooth out these PSA variations and helps us interpret the PSA undulations over time,” Dr. Loblaw said. “We are hoping that this will be a beneficial tool … to use in terms of managing patients on active surveillance.”

'All of the triggers or definitions that we looked at had a false or high trigger for treatment.'

Source Dr. Loblaw

My Take

Many Patients and Clinicians May Not Accept 20 ng/mL as Threshold

Active surveillance is a hot topic. Many men with localized prostate cancer may be candidates, but questions remain, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment?

The researchers found that a PSA above 20 ng/mL may be the most appropriate marker for switching to active treatment. But many patients would be very uncomfortable letting their PSA go as high as 20 before considering a repeat biopsy or treatment. With that strategy, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients.

We need more randomized trials—such as the multicenter START trial—that address active surveillance. I congratulate the researchers on excellent work, and look forward to further studies of and new information about active surveillance.

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men on active surveillance for prostate cancer may be overtreated if clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw said at a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

“For patients managed on active surveillance, this raises what we believe is a cautionary tale that strict follow-up with the definitions of either linear regression, threshold, or velocities may lead to a false rate of treatment for patients on surveillance who don't need it,” said Dr. Loblaw, a radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

Research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer, he said. This surveillance typically entails PSA monitoring, with initiatation of treatment often based on a PSA trigger.

The researchers tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of disease progression after a median follow-up of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%), first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%), linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%), overall PSA velocity of greater than 2 ng/mL per year (42%), and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a PSA threshold of 20 ng/mL has a low false trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, Dr. Loblaw said.

To assess PSA changes, he said, clinicians at his center have started using and are validating a general linear mixed model that is freely available online (www.asure.ca

“It allows us to smooth out these PSA variations and helps us interpret the PSA undulations over time,” Dr. Loblaw said. “We are hoping that this will be a beneficial tool … to use in terms of managing patients on active surveillance.”

'All of the triggers or definitions that we looked at had a false or high trigger for treatment.'

Source Dr. Loblaw

My Take

Many Patients and Clinicians May Not Accept 20 ng/mL as Threshold

Active surveillance is a hot topic. Many men with localized prostate cancer may be candidates, but questions remain, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment?

The researchers found that a PSA above 20 ng/mL may be the most appropriate marker for switching to active treatment. But many patients would be very uncomfortable letting their PSA go as high as 20 before considering a repeat biopsy or treatment. With that strategy, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients.

We need more randomized trials—such as the multicenter START trial—that address active surveillance. I congratulate the researchers on excellent work, and look forward to further studies of and new information about active surveillance.

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men on active surveillance for prostate cancer may be overtreated if clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw said at a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

“For patients managed on active surveillance, this raises what we believe is a cautionary tale that strict follow-up with the definitions of either linear regression, threshold, or velocities may lead to a false rate of treatment for patients on surveillance who don't need it,” said Dr. Loblaw, a radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

Research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer, he said. This surveillance typically entails PSA monitoring, with initiatation of treatment often based on a PSA trigger.

The researchers tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of disease progression after a median follow-up of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%), first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%), linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%), overall PSA velocity of greater than 2 ng/mL per year (42%), and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a PSA threshold of 20 ng/mL has a low false trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, Dr. Loblaw said.

To assess PSA changes, he said, clinicians at his center have started using and are validating a general linear mixed model that is freely available online (www.asure.ca

“It allows us to smooth out these PSA variations and helps us interpret the PSA undulations over time,” Dr. Loblaw said. “We are hoping that this will be a beneficial tool … to use in terms of managing patients on active surveillance.”

'All of the triggers or definitions that we looked at had a false or high trigger for treatment.'

Source Dr. Loblaw

My Take

Many Patients and Clinicians May Not Accept 20 ng/mL as Threshold

Active surveillance is a hot topic. Many men with localized prostate cancer may be candidates, but questions remain, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment?

The researchers found that a PSA above 20 ng/mL may be the most appropriate marker for switching to active treatment. But many patients would be very uncomfortable letting their PSA go as high as 20 before considering a repeat biopsy or treatment. With that strategy, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients.

We need more randomized trials—such as the multicenter START trial—that address active surveillance. I congratulate the researchers on excellent work, and look forward to further studies of and new information about active surveillance.