Vesna D. Garovic

A Systematic Review and Meta-Analysis of Pregnancy Outcomes in Patients with Systemic Lupus Erythematosus and Lupus Nephritis

BACKGROUND AND OBJECTIVES Studies of the impact of systemic lupus erythematosus (SLE) and its pregnancy complications have yielded conflicting results. Major limitations of these studies relate to their small numbers of patients and retrospective designs. The aim of this study was to perform a systematic literature review of pregnancy outcomes in women with SLE and a meta-analysis of the association of lupus nephritis with adverse pregnancy outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched electronic databases from 1980 to 2009 and reviewed papers with validity criteria. Random-effects analytical methods were used to evaluate pregnancy complications rates. RESULTS Thirty-seven studies with 1842 patients and 2751 pregnancies were included. Maternal complications included lupus flare (25.6%), hypertension (16.3%), nephritis (16.1%), pre-eclampsia (7.6%), and eclampsia (0.8%). The induced abortion rate was 5.9%, and when excluded, fetal complications included spontaneous abortion (16.0%), stillbirth (3.6%), neonatal deaths (2.5%), and intrauterine growth retardation (12.7%). The unsuccessful pregnancy rate was 23.4%, and the premature birth rate was 39.4%. Meta-regression analysis showed statistically significant positive associations between premature birth rate and active nephritis and increased hypertension rates in subjects with active nephritis or a history of nephritis. History of nephritis was also associated with pre-eclampsia. Anti-phospholipid antibodies were associated with hypertension, premature birth, and an increased rate of induced abortion. CONCLUSIONS In patients with SLE, both lupus nephritis and anti-phospholipid antibodies increase the risks for maternal hypertension and premature births. The presented evidence further supports timing of pregnancy relative to SLE activity and multispecialty care of these patients.

Renovascular Hypertension and Ischemic Nephropathy

Major improvements in imaging, medical therapy, and techniques of renal revascularization have changed the landscape of renovascular disease during the past decade. This has been particularly true for atherosclerotic renal artery stenosis, which remains one of the most common conditions known to accelerate hypertension and one of the most common incidentally detected vascular lesions. Despite, or perhaps because of, these developments, few clinical questions provoke more controversy and debate among cardiologists, internists, and nephrologists than decisions about the optimal management of patients with main renal artery stenosis. Even well-informed clinicians from different subspecialties hold widely divergent opinions about the role of renal revascularization, particularly for atherosclerotic disease. Studies of Medicare claims data indicate that application of peripheral intervention procedures varies >14-fold between various parts of the country.1 Some of those from interventional subspecialties (primarily interventional radiology and cardiology) emphasize the major benefits now available from endovascular procedures, including the use of stents. They argue that revascularization offers the potential to improve or reverse renovascular hypertension, to salvage or preserve the renal circulation and renal function, and to improve the management of patients with refractory forms of congestive heart failure.2 A recent review of the use of percutaneous renal artery procedures among Medicare beneficiaries confirms a rise from 7660 claims in 1996 to 18 520 claims in 2000, primarily because of a 2.8-fold increase in procedures by interventional cardiologists.3 Many in the nephrology community review the same published literature and reach nearly opposite conclusions. They argue that recent prospective studies fail to reveal major benefits of blood pressure control related to renal revascularization, that the risks of complications from interventional procedures are substantial, including uncommon but sometimes devastating loss of renal function resulting from atheroembolic disease.4 Despite a wave of enthusiasm in the early 1990s to identify …

Beyond Bar and Line Graphs: Time for a New Data Presentation Paradigm

Figures in scientific publications are critically important because they often show the data supporting key findings. Our systematic review of research articles published in top physiology journals (n = 703) suggests that, as scientists, we urgently need to change our practices for presenting continuous data in small sample size studies. Papers rarely included scatterplots, box plots, and histograms that allow readers to critically evaluate continuous data. Most papers presented continuous data in bar and line graphs. This is problematic, as many different data distributions can lead to the same bar or line graph. The full data may suggest different conclusions from the summary statistics. We recommend training investigators in data presentation, encouraging a more complete presentation of data, and changing journal editorial policies. Investigators can quickly make univariate scatterplots for small sample size studies using our Excel templates.

Hypertension in pregnancy: an emerging risk factor for cardiovascular disease

Increasing evidence indicates that hypertension in pregnancy is an under-recognized risk factor for cardiovascular disease (CVD). Compared with women who have had normotensive pregnancies, those who are hypertensive during pregnancy are at greater risk of cardiovascular and cerebrovascular events and have a less favorable overall risk profile for CVD years after the affected pregnancies. One factor that might underlie this relationship is that hypertensive disorders of pregnancy (pre-eclampsia, in particular) and CVD share several common risk factors (e.g. obesity, diabetes mellitus and renal disease). Alternatively, hypertension in pregnancy could induce long-term metabolic and vascular abnormalities that might increase the overall risk of CVD later in life. In both cases, evidence regarding risk-reduction interventions specific to women who have had hypertensive pregnancies is lacking. While awaiting results of large-scale studies, hypertensive disorders of pregnancy should be screened for during assessment of a womans overall risk profile for CVD. Women at high risk must be monitored closely for conventional risk factors that are common to both CVD and hypertensive disorders of pregnancy and treated according to current evidence-based national guidelines.

Hypertension in pregnancy as a risk factor for cardiovascular disease later in life

Objective The association between hypertension in pregnancy and future cardiovascular disease (CVD) increasingly is recognized. We aimed to assess the role of hypertension in pregnancy as an independent risk factor for hypertension, coronary heart disease (CHD), and stroke later in life. Methods Women who participated in the Phase 2 (2000–2004) Family Blood Pressure Program study (n = 4782) were categorized into women with no history of pregnancy lasting more than 6 months (n = 718), women with no history of hypertension in pregnancy (n = 3421), and women with a history of hypertension in at least one pregnancy (n = 643). We used Kaplan–Meier and Cox proportional hazard models to estimate and contrast the risks of subsequent diagnoses of hypertension, CHD, and stroke among the groups. Results Women with a history of hypertension in pregnancy, compared with those without such a history, were at increased risks for the subsequent diagnoses of hypertension (50% hypertensive at the age 53 vs. 60, P < 0.001), CHD (14% estimated event rate vs. 11%, P = 0.009), and stroke (12% estimated event rate vs. 5%, P < 0.001). The increased risk for subsequent hypertension remained significant after controlling for race, family history of CVD, smoking, dyslipidemia, and diabetes mellitus, with an adjusted hazard ratio of 1.88 [95% confidence interval (CI) 1.49–2.39, P < 0.001]. After controlling for traditional risk factors, including subsequent hypertension, the increased risk for stroke remained statistically significant (hazard ratio 2.10, 95% CI 1.19–3.71, P = 0.01), but not for CHD. Conclusion Hypertension in pregnancy may be an independent risk factor for subsequent diagnoses of hypertension and stroke.

VEGF Inhibition, Hypertension, and Renal Toxicity

The use of anti-angiogenic agents as part of the therapeutic armamentarium for advanced stage solid tumors has become the standard of care in several instances, particularly for renal cell carcinoma, non-small cell lung carcinoma, colorectal carcinoma, and gastrointestinal stromal tumors. These agents primarily target vascular endothelial growth factor (VEGF) and/or its receptors, and include bevacizumab, a humanized monoclonal antibody against VEGF, as well as tyrosine kinase inhibitors that target several receptor tyrosine kinases (RTK), including VEGF receptors. These therapies, as a general class of anti-angiogenic medications, have been shown to have common adverse vascular effects attributable directly or indirectly to their anti-VEGF effects, including hypertension, renal vascular injury, often manifested by proteinuria and thrombotic microangiopathy, and congestive heart failure. Knowledge of these common side effects and their underlying mechanisms may allow for more accurate and prompt diagnoses, timely clinical interventions, and the development of rational and standard treatments. These measures may minimize patient morbidity and mortality, not only by the treatment of side effects, but also by minimizing the disruption of treatment of the underlying malignancy, as well as improving patient quality of life.

Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test?

It is estimated that 10% of pregnancies are affected by hypertension worldwide. Approximately one-half of all hypertensive pregnancy disorders are due to preeclampsia, a pregnancy-specific disorder, its distinctive feature being either sudden onset, or worsening of pre-existing proteinuria. It has become increasingly recognized that women with a history of preeclampsia are at increased risk for future cardiovascular disease (CVD), but the mechanisms of this increase in risk are unclear. One possible explanation is that these two conditions share several common metabolic abnormalities as risk factors, including obesity, insulin resistance, and lipid abnormalities that may lead to preeclampsia and CVD at different times of a womans life. Recent studies have revealed that, similar to CVD, several mediators of endothelial cell dysfunction are up-regulated in preeclampsia. Free radical derived oxidative stress, various inflammatory markers, including neutrophil response, C-reactive protein, and leukocyte adhesion, may contribute to endothelial dysfunction in both preeclampsia and coronary atherosclerosis. Alternatively, preeclampsia itself may induce metabolic and vascular changes that may increase the overall future risk for CVD in affected women. Therefore, at present, it remains unclear whether preeclampsia is a formal risk factor for CVD, or identifies women at increased risk for CVD later in life. Pending large-scale studies aiming to examine the causality of this association, women with a history of preeclampsia should be counseled regarding their increased risks for hypertension and other cardiovascular sequelae later in life, followed closely and treated aggressively for modifiable CVD risk factors.

Renal artery revascularization improves heart failure control in patients with atherosclerotic renal artery stenosis

BACKGROUND Renal artery stenosis (RAS) impacts the pathogenesis and control of heart failure (HF) and may further contribute to increased cardiovascular morbidity and mortality in HF patients. However, the long-term effects of renal artery revascularization on cardiovascular outcomes in HF patients are not well studied. METHODS The prevalence of HF and its effects on all-cause mortality were studied in 163 consecutive patients with systemic hypertension and chronic kidney disease (serum creatinine >2 mg/dL) who underwent percutaneous transluminal renal angioplasty (PTRA) with stenting for atherosclerotic RAS. In addition, in 100 patients with RAS and coexistent HF, we compared the impact of medical treatment (n = 50) versus PTRA (n = 50) on clinical outcomes. RESULTS HF (predominantly normal ejection fraction) was present in 50/163 (31%) patients with systemic hypertension and chronic kidney disease (serum creatinine >2 mg/ dL) undergoing PTRA for RAS and represented the major predictor of all-cause mortality in these patients. When compared with sex-matched RAS and HF patients treated medically, PTRA with stenting was associated with a significant decrease in the New York Heart Association Functional Class (1.9 +/- 0.8 versus 2.6 +/- 1.0, P < 0.04) and a 5-fold reduction in the number of hospitalizations. However, renal artery revascularization did not impact mortality. CONCLUSION HF was present in one-third of patients with renal dysfunction and atherosclerotic RAS who were referred for PTRA. The presence of HF was associated with a significantly increased risk of death after PTRA with stenting. Renal artery revascularization resulted in improved HF control and a reduction in HF hospitalizations.

Maternal and foetal outcomes in pregnant patients with active lupus nephritis.

The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and foetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity and maternal and foetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria >0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria <0.5 mg/day and inactive urinary sediment. We identified 58 patients with 90 pregnancies. Compared with pregnancies in SLE patients without renal involvement (n = 47), pregnancies in patients with active lupus nephritis (n = 23) were associated with a higher incidence of maternal complications (57% vs 11%, P < 0.001), whereas those with quiescent lupus nephritis (n = 20) were not (35% vs 11%, P = 0.10). Women with active lupus nephritis were more likely to deliver preterm than women without lupus nephritis, median of 34 weeks vs 40 gestational weeks, respectively (P = 0.002) and were more likely to suffer foetal loss (35% vs 9%, P = 0.031). Active, but not quiescent, lupus nephritis during pregnancy is associated with a higher incidence of maternal and foetal complications compared with pregnancies in SLE patients without renal involvement.

Contrast Nephropathy After Coronary Angiography

Contrast nephropathy after coronary angiography is associated with considerable morbidity and mortality. We discuss the incidence, definition, and pathologic mechanisms of contrast nephropathy; provide an overview of risk factors; highlight proven preventive interventions; clarify which interventions have shown no benefit; and discuss future possibilities. The prevention of contrast nephropathy is crucial for the care of patients undergoing coronary angiography and should be possible with an understanding of risk factors and proven management strategies.