Studies On Low Blood Pressure

Overview
In this chapter, we will show you how to locate peer-reviewed references and studies on low blood pressure.
The Combined Health Information Database
The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and low blood pressure, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “low blood pressure” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search:
• Heart in Uremia: Role of Hypertension, Hypotension, and Sleep Apnea
Source: American Journal of Kidney Diseases. 38(4 Supplement 1): S38-S46. October 2001.
Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000.
Summary: Cardiovascular disease is the leading cause of morbidity (illness) and mortality (death) in patients with end stage renal (kidney) disease (ESRD). The causes of this morbidity and mortality include those usually found in the general population, those related to the uremic status, and those related to dialysis treatment. This article focuses on the specific roles of hypertension (high blood pressure), hypotension (lowblood pressure), anemia (low levels of hemoglobin, the oxygen carrying parts of the blood), hypoalbuminemia (low levels of protein in the blood), malnutrition, dyslipidemia (unhealthy levels of fats in the blood), reactive C protein, calcium-phosphate product, dialysis modalities (hemodialysis versus peritoneal dialysis), and hyperhomocysteinemia. The authors put special emphasis on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography has some risks, is expensive, and should be reserved for patients having symptoms of heart failure, patients with diabetes mellitus, or patients entering a transplantation list. This allows patients with coronary disease to undergo revascularization (adding blood vessels) through coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures. 2 figures. 1 table. 36 references.
• Achievement and Safety of a Low Blood Pressure Goal in Chronic Renal Disease: The Modification of Diet in Renal Disease Study Group
Source: Hypertension. 29(2): 641-650. February 1997.
Contact: Available from American Heart Association. 7272 Greenville Avenue, Dallas, TX 75231-4596.
Summary: The Modification of Diet in Renal Disease Study (MDRDS) showed a beneficial effect of a lower than usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. This article reports on a study which analyzed the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions in the MDRDS. Patients (n = 585) were randomly assigned to either a usual or low BP goal (mean arterial pressure less than 107 or less than 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin converting enzyme (ACE) inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean of the arterial pressures during followup in the low and usual BP groups was 93,.0 and 97.7 mm Hg, respectively. Followup BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure greater than 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion greater than 1 g per day, age greater than 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were not significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1 mm Hg increase in followup systolic BP was associated with a 1.35 times greater risk of hospitalization for cardiovascular or cerebrovascular disease. The authors conclude that lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. 1 figure. 7 tables. 40 references. (AA-M).
• Topsy-Turvy World of Postural Hypotension
Source: Diabetes Forecast. 52(3): 76-79. March 1999.
Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org.

Summary: This article discusses the problem of postural hypotension. The symptoms of this condition, which is low blood pressure caused by standing up, include dizziness, light-headedness, blurred vision, weakness, and fatigue. People who have diabetes may experience postural hypotension as a complication of autonomic neuropathy. As autonomic neuropathy progresses, the autonomic nervous system loses its reactive ability, so people who have this complication can experience rapidly changing highs and lows in blood pressure that make their head swim. The article explains how the body normally maintains blood pressure when a person stands and how it reacts in those who have autonomic neuropathy. Although physicians can perform some tests that will help determine if a person has postural hypotension, this condition is not something that physicians recognize well. If a diagnosis of postural hypotension is made, the next step is to figure out what is causing it and how to treat it. Regardless of whether autonomic neuropathy or other factors are the cause of postural hypotension, much of the treatment focuses on relieving the symptoms and removing factors that may aggravate the condition. Drugs may also be used to the condition. The article also addresses the issue of treating postural hypotension in people who also have hypertension and stresses the need to tailor treatment for postural hypotension to a person's specific needs.
• Low Blood Pressure and Incidence of Dementia in a Very Old Sample: Dependent on Initial Cognition
Source: JAGS. 47(6): 723-726. June 1999.
Summary: This population-based study of 304 nondemented people in Sweden, aged 75 to 96 years at baseline, examined whether initially low blood pressure is related to the incidence of dementia. DSM-III-R criteria were used for dementia with Hachinski's scale being used for a differential diagnosis between Alzheimer's disease (AD) and vascular dementia. Criteria for AD were similar to those of the NINCDS-ADRDA criteria. The diagnosis of dementia was given after consensus among three independent physicians. Arterial blood pressure, antihypertensive drug use, and medical histories were determined. The Cox proportional hazards regression model was used to calculate the relative risk of developing dementia in relation to baseline blood pressure levels. After an average of 3 years, 81 dementia cases were identified. Those with systolic pressure equal to or greater than 140 mm Hg had a significantly higher risk of dementia and AD. A baseline Mini-Mental State Examination (MMSE) of less than 24 significantly predicted the occurrence of dementia, and systolic pressure equal to or greater than 140 mm Hg was significantly related to MMSE scores of less than 24 at baseline. These results suggest that low blood pressure may be an early correlate of a dementing process, although researchers believe a causative effect cannot be definitely ruled out. 2 tables, 21 references. (AA-M).
Federally Funded Research on Low Blood Pressure
The U.S. Government supports a variety of research studies relating to low blood pressure. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable
database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions.
Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to low blood pressure.
For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore low blood pressure. The following is typical of the type of information found when searching the CRISP database for low blood pressure:
• Project Title: BIOCHEMISTRY AND GENETICS OF HYPERTENSION
Principal Investigator & Institution: Rapp, John P.; Professor and Chairman; Physiology/Molecular Medicine; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804
Timing: Fiscal Year 2001; Project Start 01-JUN-1988; Project End 30-MAY-2003
Summary: The overall objective is to identify-the loci which cause genetic differences in blood pressure in the rat. Because hypertension in animals and humans is a complex polygenic disease it can best be understood genetically in animals where controlled breeding is possible. We have focused our genetic studies on candidate genes in the inbred Dahl salt-hypertension sensitive (S) and inbred Dahl salt-hypertension resistant (R) rats. Genetic polymorphisms are sought at the DNA level in or near genetic loci thought (on the basis of their known biochemical/ physiological actions) to be relevant to blood pressure regulation. It is determined if a component of blood pressure and genotypes at the candidate locus cosegregate in populations derived from crosses of S and R, or S and other contrasting "control" strains. If so, this establishes the candidate locus (or an unknown closely linked locus) as a cause for genetic differences in blood pressure. DNA sequence analysis of the candidate alleles involved is then required to find a structural difference that is likely to have functional consequences with regard to blood pressure. If cosegregation is negative the candidate locus can be rejected as causing blood pressure differences provided the experiments have adequate statistical power and several different populations are studied. For candidate loci which cosegregate with blood pressure, the result will be con-firmed by the production of congenic strains. The low blood pressure allele from a control strain is transferred to the S genetic background by the standard genetic technique of repeated backcrossing to S with counter selection for the low blood pressure allele. The congenic S strain should have lower blood pressure than the parental S strain if in fact the allele transferred lowers blood pressure. "Double congenic" strains will be produced by crossing two single congenics each of which carries genes for low blood pressure at different loci on the S genetic background. Comparisons of blood pressure among double and single congenics with the parental S strain will allow definition of interactions between the loci involved. Initial studies show that such interactions are required for really high levels of genetically regulated blood pressure to be achieved. It is likely that understanding such complexity requires animal breeding techniques, and cannot be initially unraveled in work with humans.
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

• Project Title: BLOOD PRESSURE CANDIDATE GENE SCREENING--A NEW PARADIGM
Principal Investigator & Institution: Cicila, George T.; Physiology/Molecular Medicine; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804
Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003
Summary: (Adapted from the Investigator's Abstract) The essential mechanisms (and the genes underlying them) leading to hypertension need identification for better understanding and treatment of this complex disorder. The most direct way of accomplishing this is to identify genes regulating blood pressure in animal models of genetic hypertension. The applicants have linked loci on rat chromosomes 3 and 7 to blood pressure quantitative trait loci (BP QTL) in a segregating population bred from inbred Dahl salt-sensitive (S) and salt-resistant (R) rats fed a high salt diet. Introgression of R-rat derived chromosomal regions containing these two QTLs into S rats resulted in congenic strains with significantly lower blood pressure and cardiac mass compared to S rats, confirming the presence of BP QTL in the introgressed regions of chromosomes 3 and 7. Similar methodology has been used by others to develop congenic strains carrying BP QTLs located on six other chromosomes, resulting in a panel of eight congenic strains derived from the Dahl rat model of blood pressure salt-sensitivity. The applicant hypothesizes that gene(s) underlying a given BP QTL may be differentially expressed in target organs/tissues. If so, such a gene should also be differentially regulated in congenic strains carrying different BP QTL. Gene(s) responsible for a QTL's effect should show a congenic strain-specific differential-pattern of expression in a target organ(s) and should map to the chromosomal interval carried by that particular congenic strain. Therefore, genes having such characteristics will be superior candidates as genes responsible for, at least in part, a specific BP QTL. The applicant proposes to identify candidate genes for BP QTL as follows: Differentially expressed genes will be identified in the kidneys of S and R rats, on both low NaCl (genetic-differences) and high NaCl diets (salt-responsive). Renal RNA expression of such differentially-expressed genes will be examined in a panel of congenic strains carrying Dahl rat BP QTL, where each strain carries a low blood pressure allele for a different BP QTL on a background of S-rat alleles. Genes having a congenic strain-specific pattern of differential gene expression will be mapped to determine their genomic location. Genes with a 1) congenic strain-specific pattern of differential gene expression and 2) mapping to the introgressed chromosomal region containing a specific BP QTL, will be considered strong candidates for the gene(s) responsible for blood pressure differences associated with this QTL. This new approach should accelerate the identification of strong candidate genes for particular BP QTL and, potentially, of new blood pressure regulatory mechanisms.
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen