Antihypertensive medication use and risk of renal cell carcinoma.
ABSTRACT: Use of antihypertensive medications has been associated with renal cell carcinoma (RCC), but it is unclear whether specific types of medications increase RCC risk independent of the effect of hypertension, or whether the association varies by histologic subtype. To address this question, we analyzed data from a U.S. population-based case-control study of RCC.We collected information on participants' use of drugs to treat hypertension, heart problems, weight control, and swelling. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for each of four major drug classes, separately for participants with (643 cases, 443 controls) and without (500 cases, 718 controls) a history of hypertension, using unconditional logistic and polytomous regression models.None of the antihypertensive drug types was associated with RCC overall. Among participants with a history of hypertension, papillary RCC was associated with long-term use of diuretics (OR = 3.1, 95% CI = 1.4-6.7 for 16+ years, 16 cases, 31 controls; P-trend = 0.014) and calcium channel blockers (OR = 2.8, 95% CI = 1.1-7.4 for 16+ years, 8 cases, 14 controls; P-trend = 0.18), while corresponding ORs for clear cell RCC were weaker (ORs 0.9 and 1.5, respectively) and nonsignificant. The only significant finding among those with no hypertension history was an association between calcium channel blockers and papillary RCC (OR = 17.9, 95% CI = 5.9-54.5) that was based on small numbers (8 cases, 9 controls). There was little evidence of an association between RCC and use of ACE inhibitors or beta blockers.Our study, while inconclusive for overall RCC, provides, to our knowledge, the first evidence supporting an association between antihypertensive medications and papillary RCC. These subtype-specific findings, although based on small numbers, warrant further investigation.
Project description:To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case-control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case-only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case-control analyses were performed to compute subtype-specific ORs for other risk factors using polytomous regression. In case-only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1-1.4 per 10-year increase), less likely to be female (OR = 0.5, 95% CI = 0.4-0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8-3.9) as compared to clear cell cases (N = 1,524). In case-control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1-1.3 per 5 kg/m(2) increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1-1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0-1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity-RCC association differs by histology.
Project description:Few studies have examined the associations of hypertension and antihypertensive medications with ovarian cancer. In particular, beta-blockers, one of the most commonly prescribed medications to treat hypertension, may reduce ovarian cancer risk by inhibiting beta-adrenergic signaling. We prospectively followed 90,384 women in the Nurses' Health Study (NHS) between 1988-2012 and 113,121 NHSII participants between 1989-2011. Hypertension and use of antihypertensive medications were self-reported biennially. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 948 ovarian cancer cases during follow-up. Similar results were observed in the two cohorts. While hypertension was not associated with ovarian cancer risk (Pooled HR?=?1.01; 95% CI?=?0.88, 1.16), current use of any antihypertensive medication was associated with slightly increased risk compared to never users (Pooled HR?=?1.18; 95% CI: 1.02, 1.37). This increased risk was primarily due to use of thiazide diuretics (Pooled HR?=?1.37; 95% CI: 1.13, 1.68). No associations were observed for beta-blockers or angiotensin-converting-enzyme inhibitors. Calcium channel blockers (CCBs) were associated with suggestively reduced risk (NHS HR?=?0.73; 95% CI: 0.53, 1.01), after adjusting for all antihypertensive medications. Associations were similar among hypertensive women and stronger for longer use of thiazide diuretics and CCBs. In conclusion, our results provided no evidence that beta-blockers were associated with reduced ovarian cancer risk. In contrast, we observed an increased risk for use of thiazide diuretics that should be confirmed in other studies.
Project description:Individuals with psoriasis have an elevated risk of hypertension, and antihypertensive medications, especially ?-blockers, have been linked to psoriasis development. However, the association of prior existing hypertension and antihypertensive medications with risk of incident psoriasis has not been assessed using prospective data.To evaluate the association of hypertension and antihypertensive medications with risk of psoriasis.We performed a prospective cohort study (June 1, 1996, to June 1, 2008) of 77?728 US women from the Nurses' Health Study who provided biennially updated data on hypertension and antihypertensive medications.Physician-diagnosed psoriasis.A total of 843 incident psoriasis cases were documented during 1?066?339 person-years of follow-up. Compared with normotensive women, women with a hypertension duration of 6 years or more were at a higher risk of developing psoriasis (hazard ratio [HR],?1.27; 95% CI, 1.03-1.57). In stratified analysis, the risk of psoriasis was higher among hypertensive women without medication use (HR,?1.49; 95% CI, 1.15-1.92) and among hypertensive women with current medication use (HR,?1.31; 95% CI, 1.10-1.55) when compared with normotensive participants without medication use. Compared with women who never used ?-blockers, the multivariate HRs for psoriasis for women who regularly used ?-blockers were 1.11 (95% CI, 0.82-1.51) for 1 to 2 years of use, 1.06 (95% CI, 0.79-1.40) for 3 to 5 years of use, and 1.39 (95% CI, 1.11-1.73) for 6 years or more of use (P for trend?=?.009). No association was found between use of other individual antihypertensive drugs and risk of psoriasis.Long-term hypertensive status is associated with an increased risk of psoriasis. Long-term regular use of ?-blockers may also increase the risk of psoriasis.
Project description:Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women.Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42-52), who reported a diagnosis of hypertension or antihypertensive medication use at any annual visit were included. Antihypertensive medications were grouped by class and examined by race/ethnicity adjusting for potential confounders in logistic regression models. A total of 1707 (51.7%) women, mean age 50.6 years, reported hypertension or used antihypertensive medications at baseline or during follow-up (mean 9.1 years). Compared with whites, blacks were almost 3 times as likely to receive a calcium channel blocker (odds ratio, 2.92; 95% CI, 2.24-3.82) and twice as likely to receive a thiazide diuretic (odds ratio, 2.38; 95% CI, 1.93-2.94). Blacks also had a higher probability of reporting use of ≥2 antihypertensive medications (odds ratio, 1.95; 95% CI, 1.55-2.45) compared with whites. Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and thiazide diuretics increased over time for all racial/ethnic groups. Contrary to our hypothesis, rates of β-blocker usage did not decrease over time.Among this large cohort of multiethnic midlife women, use of antihypertensive medications increased over time, with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers becoming the most commonly used antihypertensive medication, even for blacks. Thiazide diuretic utilization increased over time for all race/ethnic groups as did use of calcium channel blockers among blacks; both patterns are in line with guideline recommendations for the management of hypertension.
Project description:Despite their high risk of adverse cardiac outcomes, persons on long-term dialysis therapy have had lower use of antihypertensive medications with cardioprotective properties, such as angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), ?-blockers, and calcium channel blockers, than might be expected. We constructed a novel database that permits detailed exploration into the demographic, clinical, and geographic factors associated with the use of these agents in hypertensive long-term dialysis patients.National cross-sectional retrospective analysis linking Medicaid prescription drug claims with US Renal Data System core data.48,882 hypertensive long-term dialysis patients who were dually eligible for Medicaid and Medicare services in 2005.Demographics, comorbid conditions, functional status, and state of residence.Prevalence of cardioprotective antihypertensive agents in Medicaid pharmacy claims and state-specific observed to expected ORs of medication exposure.Factors associated with medication use were modeled using multilevel logistic regression models.In multivariable analyses, cardioprotective antihypertensive medication exposure was associated significantly with younger age, female sex, nonwhite race, intact functional status, and use of in-center hemodialysis. Diabetes was associated with a statistically significant 28% higher odds of ACE-inhibitor/ARB use, but congestive heart failure was associated with only a 9% increase in the odds of ?-blocker use and no increase in ACE-inhibitor/ARB use. There was substantial state-by-state variation in the use of all classes of agents, with a greater than 2.9-fold difference in adjusted-rate ORs between the highest and lowest prescribing states for ACE inhibitors/ARBs and a 3.6-fold difference for ?-blockers.Limited generalizability beyond study population.In publicly insured long-term dialysis patients with hypertension, there were marked differences in use rates by state, potentially due in part to differences in Medicaid benefits. However, geographic characteristics also were associated with exposure, suggesting clinical uncertainty about the utility of these medications.
Project description:This study aimed to describe the management of antihypertensive medications in pregnancy by general practitioners in the UK and compare it with current guidelines.We used electronic medical records from The Health Improvement Network database from 1996 to 2010 to identify completed pregnancies. The study cohort included the first pregnancy identified during the study period in women aged 13-49?years. Information on both hypertension diagnoses and prescription of specific antihypertensive medications within the 90?days before the last menstrual period (LMP) and during pregnancy was ascertained from electronic medical records.Among 148,544 eligible pregnancies, we identified 1995 (1.3%) during which the women had pre-existing hypertension diagnosed by the LMP date. Overall, the prevalence of antihypertensive medications during the first trimester was 1.5%; beta-blockers were the most commonly prescribed antihypertensive. Among women with pre-existing hypertension, 36% were prescribed an antihypertensive medication during the 90?days before the LMP. Among those, 9.6% and 22.2% had discontinued their medication by the first and second trimesters, respectively. For contraindicated drugs such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, the corresponding discontinuation rates were around 25% and 70%. Women who switched therapy received preferably either methyldopa or an alpha/beta-blocker.In this population of UK pregnant women, prescription patterns of antihypertensive medications were dominated by recommended treatments, although some patients continued on contraindicated drugs throughout pregnancy or switched to preferred agents in a delayed fashion.
Project description:BACKGROUND:Although obesity is an established risk factor for renal cell carcinoma (RCC), it is unclear whether this relationship varies across histologic subtypes. METHODS:We conducted a nested case-control study within the Kaiser Permanente Northern California (KPNC) health care network, and meta-analysis combining our results with those of previously published studies. Our KPNC study included 685 RCC cases [421 clear cell; 65 papillary; 24 chromophobe; 35 other; 141 not otherwise specified (NOS)] and 4266 controls. Subtype-specific odds ratios (ORs) and 95% confidence intervals (CIs) for categories of body mass index (BMI) and were computed from the case-control data using polytomous logistic regression. Findings from this and other relevant studies were combined by meta-analysis using a random effects model. RESULTS:In the KPNC study, obesity (BMI???30?kg/m2) was associated with clear cell RCC (OR 1.5, 95% CI 1.1-2.1) and chromophobe RCC (OR 2.5, 95%CI 0.8-8.1), but not with papillary RCC (OR 1.0, 95% CI 0.5-1.9). In meta-analysis including three additional studies, a similar pattern of summary relative risks (SRR) for obesity was observed across subtypes (clear cell: SRR 1.8, 95% CI 1.5-2.2; chromophobe: SRR 2.2, 95% CI 1.3-3.7; papillary, SRR 1.2, 95% CI 0.8-1.6). CONCLUSIONS:These findings support the hypothesis that histologic subtypes of RCC possess distinct etiologic pathways, with obesity important for the development of clear cell and, possibly, chromophobe RCC, but not papillary RCC.
Project description:Conflicting data on the relationship between antihypertensive medications and falls in elderly people may lead to inappropriate undertreatment of hypertension in an effort to prevent falls. We aimed to clarify the relationships between the chronic use of different classes of antihypertensive medications and different types of falls, to determine the effect of medication dose, and to assess whether the risk of falls is associated with differences in cerebral blood flow. We assessed demographics, clinical characteristics, and chronic antihypertensive medication use in 598 community-dwelling people with hypertension, aged 70 to 97 years, then followed them prospectively for self-reported falls using monthly calendar postcards and telephone interviews. Antihypertensive medication use was not associated with an increased risk of falls. Participants reporting use of angiotensin-converting enzyme inhibitors had a significantly decreased 1-year risk of injurious falls (odds ratio, 0.62; 95% confidence interval, 0.39-0.96), whereas those using calcium channel blockers had a decreased risk of all falls (odds ratio, 0.62; 95% confidence interval, 0.42-0.91) and indoor falls (odds ratio, 0.57; 95% confidence interval, 0.36-0.91), compared with participants not taking these drugs. Larger doses of these classes were associated with a lower fall risk. Participants taking calcium channel blockers had higher cerebral blood flow than those not taking these medications. In relatively healthy community-dwelling elderly people, high doses of antihypertensive agents are not associated with an increased risk of falls.
Project description:Cardiovascular drugs impact many pathways involved in depression pathophysiology and treatment. However, their distinct impact on mood is underrecognized and the literature is conflicting. Therefore, using a very large and well-characterised sample of older adults with hypertension, we aimed to investigate the prevalence of depressive symptoms in users of different antihypertensive classes. We analysed baseline data from 14,195 older individuals with hypertension enroled in a large clinical trial. Median age was 75 years. The association of antihypertensive use by class and depression prevalence, as measured by a validated depression scale, was determined using logistic regression models. Multivariable logistic models were implemented to account for important confounding factors. Our analyses showed a positive association between depressive symptoms and the use of beta blockers (BB) (OR: 1.37; 95% CI: 1.17-1.60, p?<?0.01), compared with users of other antihypertensive classes. All other classes of antihypertensives (including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers) were not significantly associated with depressive symptoms. In secondary analysis, this relationship was stronger for lipophilic (39%) and nonselective BB (52%) compared with hydrophilic (26%) and selective medications (31%), respectively. This study adds further evidence for a probable association between BB and depression in a large sample of older adults with hypertension and no history of cardiovascular disease or heart failure. These findings should regenerate interest and increase awareness of clinicians about the possible adverse effects of these medications in an otherwise healthy older population.
Project description:Inhibitors of the vascular endothelial growth factor (VEGF) pathway frequently induce hypertension when used to treat patients with advanced renal cell carcinoma (RCC). This analysis characterizes hypertension and hypertension-related events in patients treated with the VEGF pathway inhibitors axitinib or sorafenib in the AXIS trial. AXIS was a randomized phase III study of axitinib versus sorafenib in patients with metastatic RCC following failure of one prior systemic regimen. Patients with uncontrolled hypertension were excluded, but patients with hypertension controlled with antihypertensive medication were allowed to participate. Guidelines for hypertension management included adjustment or addition of antihypertensive medications and/or axitinib or sorafenib dose reductions, interruptions, or discontinuations. Treatment-emergent all-causality hypertension occurred in 145 (40.4 %) axitinib-treated patients (N?=?359) and 103 (29.0 %) sorafenib-treated patients (N?=?355), with grade 3 hypertension reported in 55 (15.3 %) and 38 (10.7 %) patients, respectively, and grade 4 hypertension reported in one (0.3 %) patient in each arm. Hypertension-related events led to axitinib dose interruptions (n?=?46; 12.8 %), dose reductions (n?=?16; 4.5 %), or discontinuations (n?=?1; 0.3 %). Approximately 50 % of axitinib-treated patients with grade 3 or 4 hypertension continued treatment for ? 9 months. Hypertension-related sequelae occurred in <1 % of axitinib-treated patients. Hypertension was more frequently observed during treatment with axitinib than sorafenib in patients with RCC, but axitinib-induced hypertension rarely led to treatment discontinuation or cardiovascular sequelae. Recommendations for monitoring blood pressure and managing hypertension during axitinib therapy are presented.