Zosia Chustecka

September 27, 2011

September 27, 2011 (Stockholm, Sweden) — A large study has found that hypertension is associated with an increased risk for cancer death, and that hypertension increases the risk of developing cancer — although the latter effect reached statistical significant only in men, not women.

"The relative and absolute risk estimates were rather modest," said lead researcher Mieke Van Hemelrijck, PhD, from the cancer epidemiology group at King's College London, United Kingdom.

"This is important from a public health perspective, since a large proportion of the population in many western countries suffers from hypertension," she told delegates at a presidential session here at the 2011 European Multidisciplinary Cancer Congress. The paper was chosen as one of the best abstracts from the meeting.

One of the implications of this finding is the opportunity it offers for intervention, said Per Hall, MD, PhD, medical oncologist and professor of epidemiology at the Karolinksa Institute in Stockholm, Sweden, who acted as discussant for the paper.

"Primary prevention strategies developed by cardiologists have the potential to lower the risk of cancer," Dr. Hall explained.

For oncologists, this highlights the need for a more holistic approach, he continued. Oncologists must learn to think beyond cancer therapy and consider treatment of the whole person, including conditions such as hypertension and cardiovascular disease, he said. "If we look for other things also, it would definitely improve overall survival," he added.

Link With Hypertension

Previous studies exploring the link between hypertension and cancer have yielded mixed results, with some showing and some not showing an association, Dr. Van Hemelrijck told Medscape Medical News.

However, many earlier studies used just 1 measurement of blood pressure (BP), which can cause random error, she noted. To control for this, Dr. Van Hemelrijck and colleagues used data from a subgroup of individuals in their study (133,829 of the 577,799 participants) who had undergone several measurements of BP, and used these findings to correct for random error in the whole sample.

The researchers also controlled for smoking and obesity, which again was not controlled in some of the previous studies, and for age and sex. However, the study did not have any information on antihypertensive treatment; there were no records on whether and which drugs were being used to control BP, Dr. Van Hemelrijck noted.

Largest Study So Far

The study is the largest of its kind, analyzing data on 289,454 men and 288,345 women. The data come from Metabolic Syndrome and Cancer (Me-Can) project, which includes people from Norway, Sweden, and Austria who had undergone regular health examinations from 1972 to 2005.

After a median follow-up of 12 years, excluding the first year, cancer had been diagnosed in 22,184 men and 14,744 women, and 8724 men and 4525 women had died from cancer.

BP measurement was reported as mid-BP, which is the sum of systolic and diastolic pressure divided by 2. The average mid-BP in the study was 107 mm Hg for men and 102 mm Hg for women. The results for BP were divided into 5 groups, with individuals in the first quintile having the lowest BP and those in the fifth quintile having the highest BP.

Cox proportional hazard regression analysis showed that the risk of developing and of dying from cancer was linearly proportional to the increase in BP.

The increase in the incidence of cancer with increasing BP was statistically significant for men — specifically, the risk increased for oral, colorectal, lung, bladder, and kidney cancers, and for melanoma and nonmelanoma skin cancer. The overall risk of developing any cancer was increased by 29% between men in the lowest quintile and those in the highest quintile.

An increase was also seen in women, but did not reach statistical significance. An increase in incidence risk was seen for liver, pancreas, cervix, and endometrial cancers, and for melanoma.

Increasing BP also increased the risk of dying from cancer; this effect was statistically significant in both sexes. Men in the fifth quintile of mid-BP had a 49% increased risk for cancer death, compared with those in the lowest quintile; for women, this risk increased by 29%.

In terms of absolute risk, the increase from raised BP was rather modest, Dr. Van Hemelrijck noted. "Men with mid-blood pressure in the highest [quintile] had an absolute risk of developing cancer of 16%, compared with an absolute risk of 13% for those with mid-blood pressure in the lowest [quintile]," she said.

For cancer death, the absolute risk was 8% for men in the highest quintile, compared with 5% for men in the lowest quintile; for women, the risk was 5% in the highest quintile and 4% in the lowest quintile, she reported.

We cannot claim that there is a causal link between high blood pressure and cancer risk.

This study is observational, so "we cannot claim that there is a causal link between high blood pressure and cancer risk, nor can we say that the cause of cancer is a factor related to high blood pressure," Dr. Van Hemelrijck explained.

Hypertension might be a proxy for an unhealthy lifestyle, she speculated in comments made to Medscape Medical News. It is already established that cancer and diabetes are risk factors for cancer; hypertension might be part of the whole metabolic syndrome, which increases the risk, rather than just a factor on it's own, she said.

She did note that a meta-analysis reported some years ago (Am J Med. 2002;112:479-486) specifically linked hypertension to an increase in the risk for kidney cancer. In that case, a causality is perhaps more understandable because high BP increases the stress on the kidney.

The meta-analysis analyzed data from 10 studies (47,119 patients), and found that hypertension was associated with a 23% increase in the risk of dying from cancer. Those researchers found an association between hypertension and an increased risk of developing renal cancer, but not with cancer at any other site. The adjusted odds ratio for renal cell cancer among hypertensive patients, relative to their normotensive counterparts, was 1.75.

One of the coauthors on that meta-analysis, Franz H. Messerli, MD, FACC, FACP, professor of clinical medicine at the Columbia University College of Physicians and Surgeons and division of cardiology at St. Luke's-Roosevelt Hospital in New York City, was asked to comment on the study by Dr. Van Hemelrijck's team. "Since this is the largest study so far linking hypertension to cancer, it has be looked at thoroughly. However, in my opinion, the issue remains a can of worms," he told Medscape Medical News.

"We should remember that hypertension may not only be a proxy for an unhealthy lifestyle, as the authors state, but also a proxy for more frequent visits to physicians. The more often patients are seen by physicians, the greater the odds of malignancies being diagnosed," Dr. Messerli explained.

In addition, he pointed out that "patients with hypertension are commonly on antihypertensive therapy for years and decades. The long-term safety of antihypertensive drugs has not been well documented, since most safety studies only last 3 to 5 years. The present study did not provide any information on antihypertensive treatment. Thus, we don't know whether the link between hypertension and cancer was due to the blood pressure elevation per se, its treatment with various drugs, the "unhealthy lifestyle," or even to the more frequent physician visits."

"Clearly, studies like this one,...however thorough and well done, may create more heat than light and are prone to confuse patients and physicians alike," Dr. Messerli opined.

Modest Effect

Jan Willem Coebergh, MD, PhD, professor of cancer surveillance at the Eindhoven Cancer Registry in the Netherlands, and spokesperson for the European CanCer Organisation, said in a statement that "this extensive population-based study on the role of concomitant hypertension shows that it has a modest effect on the risk of certain cancers, especially the kidney and colorectum, but it is probably a smaller effect than that caused by diabetes and various vascular conditions."

Franco Berrino, MD, from the Instituto Nazionale Tumori in Milan, Italy, and spokesperson for the European Society of Medical Oncology, said that "there is increasing evidence that metabolic syndrome is associated with a higher risk of developing cancer, as well as other chronic diseases. As an unhealthy lifestyle is a major determinant of hypertension, these results from the highly productive Me-Can project add to the evidence that lifestyles affect both the risk and prognosis of cancer."

2011 European Multidisciplinary Cancer Congress (EMCC): Abstract 4LBA. Presented September 27, 2011.

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