ArticlesRelation between drug treatment and cancer In hypertenslves in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial
Introduction
For more than 25 years, the risk of cancer in relation to use of antihypertensive drugs has been much discussed. Retrospective case-control studies and subgroup analyses from prospective intervention trials have suggested that several antihypertensive regimens (eg, reserpine, diuretics, β-blockers, angiotensin-converting enzyme [ACE] inhibitors, and calcium antagonists) are associated with an increased cancer risk in the breast, kidney, and gastrointestinal tract, as well as with multiple cancer forms. However, these studies do not give plausible explanations for the development of multiple cancer forms from the various classes of antihypertensive drugs described. Additionally, increased risk is sometimes, but not always, related to long-term use of the drugs, and there might be a competing death risk (ie, cardiovascular vs cancer).
The most important argument is that the increased risk of cancer death is seen in treated as well as untreated hypertensive patients, raising the possibility that hypertension is itself a risk factor for cancer. Dyer and colleagues1 reported that both systolic and diastolic blood pressures were related to 14-year mortality from cancer after adjustment for several factors such as age, cholesterol, and smoking. Investigators from several studies,2, 3, 4, 5 but not all,6 have pointed out that hypertension seems a moderately large risk factor for cancer in various sites. Cardiovascular risk factors such as obesity, diabetes, and smoking seem to interact with increased blood pressure in a complex way and act as risk factors for cancer.2, 7 Potential mechanisms that might contribute to an increased risk of cancer in hypertensive patients are unknown. In human beings and animals, the response to carcinogens can differ between those with hypertension and those with normal blood pressure.8, 9
There has been much debate about the possible increase in risk of cancer after treatment with calcium antagonists, and researchers have also postulated that there is an association between renal cell carcinoma and use of diuretics.10 Therefore, we decided to analyse the frequency of cancer in elderly patients who participated in the Swedish Trial in Old Patients with Hypertension 2 (STOP-Hypertension-2). This 5-year prospective study was originally designed to compare cardiovascular mortality in elderly hypertensive men and women randomly assigned to three different treatment strategies: conventional drugs (diuretics or β-blockers), calcium antagonists, or ACE inhibitors.11, 12, 13
Section snippets
Methods
We have previously reported the study population, design, and main results of STOP-Hypertension-2.11, 12, 13 Briefly, between Sept 1, 1992, and Dec 30, 1994, we enrolled 6614 elderly patients (mean age 76 years, range 70–84 at baseline) from 312 health centres in Sweden (of about 850). The mean and median follow-up time was 5·0 years and 5·3 years, respectively. Follow-up with respect to occurrence of cancer and vital status ended on Dec 31, 1998; no patient was lost.13 Table 1 shows some
Results
The overall mortality rate of the STOP-Hypertension-2 cohort was lower than that of the general Swedish population (table 2), but this difference diminished over time. At baseline, according to National Cancer Registry data, 607 patients had a history of previous malignant disease, 43 of whom had two cancers (table 1). The prevalence was thus 9%. The diagnoses listed in table 1 represents about 80% of all cancers in the cohort and are closely related to the distribution of cancer types that
Discussion
We saw no significant deviation from the expected number for any cancer type. There was no increase in the frequency of cancer during the first part of the study, which might have been expected because patients had more frequent visits to the health centre than usually take place.
When comparing with the general population, we only matched for age, sex, and calendar-year, and thus did not adjust for risk factors such as obesity, smoking, previous smoking, alcohol, &c, or for possible protective
References (29)
- et al.
High blood-pressure: a risk for cancer mortality?
Lancet
(1975) - et al.
Hypertension, age, and smoking related to genotoxic sensitivity in human lymphocytes: a population study
Environ Res
(1986) - et al.
Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2
Lancet
(1999) - et al.
Morbidity and mortality in the Swedish trial in Old Patients with Hypertension (STOP-Hypertension)
Lancet
(1991) - et al.
Do inhibitors of angiotensin-I-converting enzymes protect against risk of cancer?
Lancet
(1998) - et al.
Do calcium channel blockers increase the risk of cancer?
Am J Hypertens
(1996) - et al.
Calcium-channel blockade and incidence of cancer in aged populations
Lancet
(1996) - et al.
Calcium channel blockers and risk of cancer
Lancet
(1997) - et al.
Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension
Lancet
(1997) - et al.
Abdominal body mass distribution and elevated blood pressure are associated with increased risk of death from cardiovascular cancer in middle-aged men: the results of a 15-to 20-year follow-up in the Paris prospective study I
Int J Obes
(1993)
Hypertension and long-term cancer incidence and mortality among Swedish men
J Hypertens
Hypertension, antihypertensive drugs, and mortality from cancer among women
J Hypertens
Hypertension and hormone-related neoplasms in women
Hypertension
The association of blood pressure with cancer incidence in a prospective study
Am J Epidemiol
Cited by (101)
Cancer and Cardiovascular Risk in Women With Hypertensive Disorders of Pregnancy Carrying a Common IGF1R Variant
2020, Mayo Clinic ProceedingsCitation Excerpt :The expected microRNA blunting of IGF1R messenger RNA expression levels for the T allele can be seen in multiple types of normal human tissues within the Genotype-Tissue Expression databases.22 Although it is remotely conceivable that the observed lower risk for nonbreast cancer might be secondary to HDP-linked HTN, this seems unlikely because HTN and its treatments have nil to weak associations with cancer development in women, with the possible exception of renal cancer.46-49 The likelihood of a lasting organ effect by HDP exposure is supported in part by previous findings that pregnancy can produce durable epigenetic tissue changes mediated by gene methylation.50
Beyond the boundaries of cardiology: Still untapped anticancer properties of the cardiovascular system-related drugs
2019, Pharmacological ResearchAnti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis
2018, Critical Reviews in Oncology/HematologyCalcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence
2017, Cancer EpidemiologyCitation Excerpt :In others, hypertension or use of AHTs was adjusted for in the analysis [40] and/or a sub-analysis was conducted restricting to only participants with hypertension and/or taking AHTs [35,37,38,45,46,50]. The majority of included studies found no association between CCB use and breast cancer, beyond that which could be explained through chance [33–35,39–41,43,47–49,51,52,54–62]. In contrast, the findings of eight studies suggested a positive association between CCB use and breast cancer, to varying degrees [36–38,42,44–46,50].