Ankylosing spondylitis: An important cause of severe disturbances of the cardiac conduction system: Prevalence among 223 pacemaker-treated men

The cause of severe disturbances of the cardiac conduction system is seldom possible to establish clinically at pacemaker implantation, apart from cases of acute myocardial infarction or digitalis intoxication and in relatively rare cases of inflammatory disorders such as sarcoidosis and systemic sclerosis. Since cardiac manifestations, mainly conduction disturbances, occur in patients with ankylosing spondylitis, the prevalence of this disease was determined using radiologie screening for sacroillitis in a population of 223 men who had permanently implanted pacemakers. Sacroillitis was found in 19 men (8.5 percent), 15 of whom fulfilled the diagnostic criteria for ankylosing spondylitis. In six patients, sacroillitis was asymptomatic and two of the patients were completely free of symptoms other than those originating from their heart manifestations. In seven of the 15 patients with ankylosing spondylitis and in the four patients with sacroillitis without clinical criteria of ankylosing spondylitis, the diagnosis was previously unknown. Uveltis and aortic regurgitation occurred in five patients each, while peripheral arthritis was twice as common. The prevalence of sacroillitis and ankylosing spondylitis of 8.5 and 6.7 percent, respectively, differ significantly (p < 0.01) from the frequencies found in general Caucasian populations of 1 to 2 and 0.1 to 0.5 percent, respectively. HLA B27 was present in more than 80 percent of the patients with sacrolilltis and/or ankylosing spondylitis, compared with 8 to 10 percent in the general population. This strong association is in accordance with previous studies of patients with symptomatic sacroillitis and/or ankylosing spondylitis. Thus sacroillitis, diagnosed by x-ray, can be considered a marker for this relatively common rheumatic cause of severe disturbances of the cardiac conduction system.     

HLA B27-associated rheumatic diseases with severe cardiac bradyarrhythmias. Clinical features and prevalence in 223 men with permanent pacemakers

A 15-fold increase in the prevalence of ankylosing spondylitis in a group of 223 men with permanent cardiac pacemakers has recently been demonstrated. In this study of the same patient group, the prevalence of other related rheumatic syndromes was investigated by clinical examination and HLA typing. The clinical picture and electrocardiographic features of all patients with HLA B27-associated rheumatic disease (seronegative spondarthritis) were analyzed. Altogether 28 patients, 12.6 percent (95 percent confidence limits: 8.2 to 17.0 percent), fulfilled inclusion criteria for seronegative spondarthritides; 15 had ankylosing spondylitis. The seronegative spondarthritides previously had been diagnosed in less than 50 percent of the patients. Twenty-two (85 percent) of the 26 HLA-typed patients were B27-positive, implying a very strong association with this genetically determined cell surface protein. Patients with severe bradyarrhythmias associated with the seronegative spondarthritides were thus found to constitute a large proportion of the 223 men with permanent pacemakers. A high frequency of aortic regurgitation and all kinds of bradyarrhythmias were found. Twenty patients had complete heart block--in a majority, occurring intermittently, but otherwise without distinguishing features.     

HLA-B27-associated heart disease. Clinicopathologic study of three cases

The histologic features of the cardiac lesions in HLA-B27-associated heart disease were examined in three cases that illustrate different nuances of the clinical spectrum of this disorder. One of these cases constitutes an important link between the previously established concept of cardiac manifestations in ankylosing spondylitis and Reiter's disease and the recently introduced, wider concept of HLA-B27-associated cardiac manifestations. A correlation between the invasive electrophysiologic results and the autopsy findings is demonstrated in another case.     

Experience with pindolol, a betareceptor blocker, in the treatment of hypertension.

Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, were studied at rest and during work before and after an average of two and 16 months of oral treatment with the beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, both at rest and during work. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: (1) a negative chronotropic effect on the heart, (2) a decrease in peripheral vascular resistance, and (3) an increase in venous capacitance affecting the venous return. However, the significance of these mechanisms seems to differ when the situations after two months of treatment are compared with those after 16 months of treatment. In the beginning, a decrease in cardiac output seems to be the main cause of the lowering of the blood pressure; later, a decrease in systemic vascular resistance might be of greater importance.     

Sodium wasting, acidosis and hyperkalemia induced by methicillin interstitial nephritis. Evidence for selective distal tubular dysfunction.

A 61 year old male patient was studied who manifested dehydration, azotemia, acidosis and hyperkalemia six weeks after exposure to methicillin. Thyroid and adrenal glucocorticoid and mineralocorticoid function were normal. The dehydration was found to be caused by a profound sodium-losing nephropathy; urinary sodium ranged from 78 to 101 meq/day during a salt restricted diet. A distal renal tubular acidosis and a quantitively impaired ability to excrete potassium were also found. These defects were relatively unresponsive to mineralocorticoid or prednisone therapy. A renal biopsy specimen showed an interstitial nephritis which selectively affected distal tubules and was thought to be secondary to methicillin. The data suggest functional impairment specific for the distal tubule, but with only a modest decrease in the glomerular filtration rate.     

Peptide hormone markers in screening for endocrine tumors in multiple endocrine adenomatosis type I

In three families with the multiple endocrine adenomatosis type I (MEA I) trait, 51 members were investigated by measurement of circulating peptide hormones as tumor markers. Twenty-five of 51 members (49 percent) were considered to be affected by MEA I disorders. The incidence rose with age (75 percent in generation II). Both sexes were affected equally. Hyperparathyroidism was present in 20 of 25 affected members (80 percent), and pituitary tumors (prolactinomas) were found in four of 25 (16 percent). Endocrine pancreatic tumors were found in nine of 25 affected members (36 percent), but when "probable" tumors (seven) are included the frequency rises to 72 percent. Hyperparathyroidism was found in all except one member with proved lesions in other organs. Among patients with proved and possible endocrine pancreatic tumors, elevated serum levels of gastrin and pancreatic polypeptide were frequently found, 78 percent and 67 percent, respectively, and we suggest that serum gastrin and pancreatic polypeptide levels are the most useful screening markers at present for pancreatic lesions in MEA I.     

Effect of cholic acid feeding on bile acid kinetics and neutral fecal steroid excretion in hyperlipoproteinemia (types II and IV)

Bile acid kinetics and the fecal excretion of neutral steroids were characterized in ten hyperlipemic patients before and after oral administration of 0.8–1.0 g cholic acid per day for 2–3 wk. Prior to cholic acid feeding, the turnover of cholic acid in the five patients with type II hyperlipoproteinemia (178 ± 65 mg/day) was significantly less than in the five with a type IV lipoprotein pattern (700 ± 270 mg/day). The two groups did not differ with regard to pool size and half-life of cholic acid or pool size, half-life, and turnover of chenodeoxycholic acid.The administration of cholic acid to the patients with type II hyperlipoproteinemia resulted in a markedly elevated cholic acid pool size. This change was associated with a decreased pool size and a decreased turnover of chenodeoxycholic acid, a reduced serum cholesterol level, and an increased excretion of neutral steroids in feces. In contrast, only three of the subjects with a type IV lipoprotein pattern displayed an increased cholic acid pool size; the chenodeoxycholic acid turnover fell in four and the fecal excretion of neutral steroids tended to increase in all five. It was concluded that patients with types II and IV hyperlipoproteinemia differ in their capacity to retain the cholic acid administered. The type II group has the ability to control chenodeoxycholic acid synthesis by feedback inhibition during oral administration of cholic acid. This may be the case for the type IV group, too, although this was not significantly proven by the present study.     

TUSARC: Prognostic Value of High-Sensitivity Cardiac Troponin T Assay in Asymptomatic Patients with High Cardiovascular Risk

BackgroundPrognostic value of high-sensitivity cardiac troponin T (hs-cTnT) assays have been assessed in selected populations in different studies and in registries of members of the general population with low cardiovascular risk. The aim of this study was to determine the prognostic value of hs-cTnT in an asymptomatic very-high cardiovascular risk Spanish population.MethodsFrom a previous prospective cohort of the TUSARC (troponina T UltraSensible en pacientes Asintomáticos de alto Riesgo Cardiovascular) registry, follow-up was conducted in 602 patients (93.18%). The association of high hs-cTnT (≥99th percentile value) and incidence of primary event was studied. A primary event was defined as a combined major cardiovascular event (incidence of cardiovascular death, decompensated heart failure, non-fatal cerebrovascular event, non-fatal myocardial infarction, or coronary revascularization). The association between high hs-cTnT and incidence of secondary events was studied as well.ResultsIn patients with high hs-cTnT, the incidence of primary event during follow-up was significantly higher (18.30% vs 3.67% P < .001): heart failure (6.25% vs 0.73% P < .001), cardiovascular death (7.29% vs 0.00% P < .001), and death from any cause (7.81% vs 0.98% P < .001).ConclusionsIn an asymptomatic very-high cardiovascular risk Spanish population, elevated hs-cTnT was significantly associated with incident major cardiovascular combined end point and incidence of heart failure, cardiovascular death, and death from any cause.     

Premature death and associated risk factors in urban middle-aged men

The full range of premature mortality and associated risk factors was analyzed for a follow-up period of three and a half to eight years in a uniform group of 7,935 middle-aged males (46 to 48 years old at screening) participating between the years 1975 and 1979 in the preventive population program in Malmö (participation rate 76.7 percent). Of the 218 deaths that occurred, necropsy was performed in 181 (83.0 percent). Three major causes of death were established: cancer (61/218), alcohol-related deaths (55/218), and coronary heart disease (50/218). In these three main categories of male premature mortality, significant and distinctly differential risk factor patterns were found. In coronary heart disease, smoking (p = 0.0062), serum cholesterol level (p = 0.00014), serum triglyceride level (p = 0.00013), systolic blood pressure (p = 0.000012), and diastolic blood pressure (p = 0.0021) were the strongest single determinants, but the independent role of the diastolic blood pressure disappeared in a multivariate analysis whereas all the others could be combined in a highly predictive logistic model. In the alcohol-related group, equal or stronger risk factor associations were present for serum gamma-glutamyltransferase level (p < 0.0001), questionnaire alcoholism screening response (p < 0.0001) and, inversely, serum cholesterol level (p = 0.0046) and serum creatinine level (p < 0.0001), all of which were independent and could be combined in an even more predictive logistic model than in the coronary heart disease group. In the cancer deaths, significant associations were found for serum urate level (p = 0.023) and, inversely, serum cholesterol level (p = 0.056 ? 0.031). Malignant and alcohol-related diseases constituted at least equally prominent groups as the cardiovascular disorders of the total premature deaths that occurred during middle age in these cohorts of Malmö males. All of these conditions are potentially avoidable and seem to be associated with significant and distinctive risk factor patterns. It seems possible that these factors may be applied, in current alcohol-related disorders and in future malignant diseases, both as indicators of the respective risks and as signals and instruments for directed preventive measures like the previously well established and tested methods for the regulation of blood pressure, serum lipids levels, and so on.     

Risk factors for thyroid abnormalities after neck irradiation for childhood cancer

Thyroid evaluations were performed in 95 patients who received radiotherapy to the neck region for childhood cancer five to 34 years earlier. Fifty-six patients (61 percent) had at least one abnormality of serum free thyroxine index, serum thyroid-stimulating hormone (thyrotropin), or thyroid palpation. Seven had subnormal free thyroxine index and 40 had elevated thyrotropin concentrations. Thyroidal radiation doses of 3,000 or more rads and lymphangiography independently increased the risk (p ≤ 0.01) of an elevated serum thyrotropin concentration (present in 11 percent of patients with neither risk factor, 50 percent of those who underwent lymphangiography and received less than 3,000 rads, 46 percent of those who had 3,000 or more rads and no lymphangiography, and 76 percent of those with both), but duration of follow-up did not. Twenty-six patients had thyroid nodules and six others had diffuse thyroid enlargement. The frequency of palpable abnormalities increased with the follow-up time after radiation (30 percent of patients followed up less than 10 years had abnormalities versus 43 percent of those followed up 10 or more years, p = 0.03), but was not related to the serum thyrotropin level, radiation dose, or lymphanglography. Among 10 patients who had surgery for nodules, three had localized papillary thyroid carcinomas.     

Carcinoid heart disease: Clinicopathologic findings and follow-up in 11 cases

Eleven cases of carcinoid heart disease are reported, including two in which a primary, ovarian carcinoid tumor without metastases was extirpated but tricuspid incompetence progressed. Findings on routine physical examinations, right heart catheterization, phonocardiography, electrocardiography, chest roentgenograms, right ventriculography and patho-anatomic investigation are briefly described. The natural history of carcinoid heart disease is commented upon. It is concluded that carcinoid heart disease may be a lethal manifestation of carcinoidosis even in cases in which disseminated tumor growth persists, and that it may have a progressive further course of its own even in cases in which the carcinoid tumor has been successfully surgically removed.     

Nephrotic syndrome, renal vein thrombosis and renal failure. Report of case with recovery of renal function, loss of proteinuria and dissolution of thrombus after anticoagulant therapy

A case of nephrotic syndrome, renal vein thrombosis and advanced renal failure in a 52 year old woman with adult onset diabetes mellitus is reported. The diagnosis of renal vein thrombosis was established by selective renal venography. Following 15 months of anticoagulant therapy creatinine clearance increased to the level noted prior to renal vein thrombosis, and proteinuria decreased to less than 500 mg/day. Repeat renal venography demonstrated clearing of the renal vein thrombosis. Renal biopsy performed at this time revealed changes compatible with arterial nephrosclerosis on light microscopy, but there were no findings typical of diabetic intercapillary glomerulosclerosis. No immune deposits were seen on immunofluorescent microscopy. Electron microscopy revealed fusion of the foot processes, but there were no electron dense deposits in or on the basement membrane to suggest membranous glomerulonephritis. Analysis of the sequence of events suggests that the renal vein thrombosis in this patient was probably a complication of the nephrotic syndrome, the etiology of which is not clear although the biopsy findings are compatible with lipoid nephrosis.     

Coronary angiography and left ventriculography in survivors of transmural and nontransmural myocardial infarction

Recent studies have suggested a similar prognosis for patients with transmural myocardial infarction and nontransmural myocardial infarction despite a smaller infarct size in the latter patients estimated by creatine phosphokinase (CPK). Thirty-one patients with transmural myocardial infarction and 17 patients with nontransmural myocardial infarction as defined by electrocardiographic criteria underwent coronary angiography and left ventriculography from 10 to 24 days after they had an acute myocardial infarction. Forty-three of these 48 patients were asymptomatic following their myocardial infarction. When compared to patients with nontransmural myocardial infarction, those with transmural myocardial infarction had greater peak CPK levels, 1,090 +/- 210 versus 290 +/- 60 IU (p less than 0.01). There was no difference in prevalence of single, double or triple vessel coronary artery disease, mean number of coronary arteries 50 per cent narrowed (2.0 +/- 0.2 versus 2.0 +/- 0.2), near total or total occlusions, coronary score (Friesinger) (7.9 +/- 0.6 versus 8.2 +/- 0.7), left ventricular ejection fraction (48 +/- 2 versus 53 +/- 4), or per cent of akinetic-dyskinetic myocardial segments (66 of 242 [27 per cent] versus 32 of 132 [24 per cent]) between two groups. The similar extent of coronary artery narrowing and degree of left ventricular dysfunction may explain the similar prognosis for patients with transmural myocardial infarction and those with nontransmural myocardial infarction despite differences in enzymatically estimated acute infarct size.     

Eosinopenia as an Adverse Marker of Clinical Outcomes in Patients Presenting with Acute Myocardial Infarction

BackgroundEosinopenia is considered a surrogate of inflammation in several disease settings. Following ST-segment elevation myocardial infarction, eosinopenia is presumed to be a marker of infarct severity. We sought to study the relationship between eosinopenia and infarct severity and how this relationship determined the long-term outcomes following ST-segment elevation myocardial infarction.MethodsSix hundred and six consecutive patients undergoing primary percutaneous coronary interventions from a large volume single center were enrolled. Low eosinophil count was defined as < 40 cells/mL from samples within 2 hours after reperfusion. Primary endpoint was defined as composite of death, myocardial infarction, stroke, unplanned revascularization, and readmission for heart failure over 3.5 years’ follow-up.ResultsSixty-five percent of the patients had eosinopenia. Patients in the low eosinophil group had larger infarct size as measured by troponin value (2934 vs 1177 ng/L, P < .001) and left ventricle systolic function on echocardiography (48% vs 50%, P = 0.029). There was a weak correlation between eosinophil count and both troponin (r = -0.25, P < 0.001) and ejection fraction (r = 0.10, P = .017). The primary endpoint was higher in eosinopenic patients (28.8% vs. 20.4%; hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.05 to 2.13, P = .023). A discordance between eosinopenia and severe left ventricle systolic dysfunction was observed in 55.6% of cases. Compared with normal count, eosinopenia was associated with worse clinical outcomes in patients with non-severe left ventricle dysfunction (24.1% vs 16.2%; HR 1.58, 95% CI 1.01 to 2.45, P = .044) but not in those with severe left ventricle dysfunction (42.3% vs. 38.9%; HR 1.10, 95% CI 0.59 to 2.03, P = .77) (P < .01 for interaction).ConclusionsEosinopenia is an easily determined marker that reflects worse clinical outcomes over long-term follow-up.     

Risk for liver disease in adults with alpha1-antitrypsin deficiency

Risk for the development of liver disease was estimated in 115 adults with α₁-antitrypsin deficiency, most of whom were of PI type (protease inhibitor type) Z. Seventy-one subjects were ascertained through their disease; 44 were ascertained independently of disease. A low concentration of serum prealbumin was sensitive in detecting impaired liver function and may indicate functioning cell mass, a different parameter than is measured by liver enzymes.Liver disease has usually been considered rare in adults with α₁-antitrypsin deficiency. However, the risk for the development of liver disease was relatively high for men between 51 and 60 years of age. The risk for women was lower than that for men. Our study indicates that a periodic assessment of liver function may be warranted for patients with α₁-antitrypsin deficiency who are over 40 years of age.     

Graves' disease in pregnancy years after hypothyroidism with recurrent passive-transfer neonatal Graves' disease in offspring. Therapeutic considerations

Symptoms and signs of severe hypothyroidism developed in a young woman at age 15. These symptoms progressed for a year; at age 16, she was found to have a firm goiter, thyroid autoantibodies, very low serum thyroxine and high thyrotropin values, indicating autoimmune thyroiditis with hypothyroidism. She received L-thyroxine, 0.20 mg per day, and was well until age 24 when she became pregnant. In the first trimester, manifestations indicative of hyperthyroidism developed; these were only ultimately recognized immediately after delivery of a 32-week still-born goitrous baby. Despite the discontinuation of thyroxine therapy, the hyperthyroidism persisted and was confirmed as Graves' disease by elevated thyroxine, triiodothyronine, and radioactive iodine uptake values, a diffuse scanning result, and the presence of thyroid-stimulating antibody. The patient was treated with propylthiouracil and became pregnant while receiving that regimen. Later, several months after delivery, the patient was treated with radioactive iodine, ultimately became hypothyroid, and has been treated ever since with thyroxine. She became pregnant again and, because of the continuing high titers of thyroid-stimulating antibody, received propylthiouracil, 100 mg daily, commencing in the third trimester of pregnancy, to avoid probable fetal hyperthyroidism due to the transplacental transfer of thyroid-stimulating antibody. In each of the last two pregnancies, when the infants were born, they seemed normal (because of the transplacental effect of propylthiouracil), but passive-transfer neonatal hyperthyroidism developed in each within 10 days after delivery, ultimately requiring treatment by conventional means. This case illustrates the following points: (1) Hyperthyroidism occasionally develops years after hypothyroidism. (2) In young women, high titers of thyroid-stimulating antibody may produce fetal and neonatal passive-transfer hyperthyroidism even at a time when the mother herself is no longer hyperthyroid; transplacental treatment of the fetus by maternal propylthiouracil ingestion may thus be necessary during the last trimester, but only when there is a high degree of probability that the fetus is at risk. (3) Because the infants had been protected in utero by the placental transfer of propylthiouracil, neonatal hyperthyroidism did not develop until several days after delivery.(ABSTRACT TRUNCATED AT 400 WORDS)     

Herpes virus infections in patients with neoplastic disease. Diagnosis and therapy

Herpes viruses are among the most common and troublesome opportunistic pathogens infecting patients with neoplastic diseases. The recent development of partially effective and relatively nontoxic antiviral agents offers promise for the prophylaxis or therapy of these infections in high-risk groups. Vidarabine and acyclovir have shown efficacy in several herpes virus infections and are now licensed in the United States. Alpha interferon may also be useful in the prophylaxis or early therapy of certain herpes virus infections. Newer antiviral agents and combination therapies are under study. Early and rapid diagnosis of such infections is critical to the development of effective therapy.     

Evaluation and outcome of emergency room patients with transient loss of consciousness

We identified 198 patients who presented to our emergency room with transient loss of consciousness. Seizures (29 percent of patients) and vasovagal/psychogenic episodes (40 percent of patients) were the most common presumptive causes of loss of consciousness, but the cause of loss of consciousness remained uncertain even at follow-up in 11 ± 6 months in 13 percent of the patients. The history and physical examinations were sufficient for diagnosis in 85 percent of the patients in whom a diagnosis could be established. These data guided inpatient and outpatient evaluations that led to the correct diagnoses in all patients with potentially dangerous causes of loss of consciousness except for one patient who had pulmonary embolism. In selected patients, diagnostic lests such as blood chemistries (three patients), electrocardiograms (four patients) electroencephalograms (three patients), and Holter monitoring (four patients) provided crucial information, and CT scans identified new brain tumors in four patients with focal neurologic presentations. At the time of follow-up, 7.5 percent of patients had suffered either major morbidity or death related to the cause of the index episode of loss of consciousness. Patients with cardiac causes represented a high risk (33 percent) group for such poor outcome, whereas patients who were under age 30, or who were under age 70 and had loss of consciousness on a vasovagal/psychogenic or unknown basis, constituted a low risk (1 percent) subgroup.     

Diabetic ketoacidosis. Induction of hypocalcemia and hypomagnesemia by phosphate therapy.

A nine year old boy with previously undiagnosed diabetes mellitus presented with severe ketoacidosis. His hyperglycemia (plasma glucose = 786 mg/dl), acidosis (arterial pH = 6.86), dehydration and coma responded well to therapy with intravenous fluids, bicarbonate and insulin. Potassium supplementation was given as a phosphate salt.Despite marked clinical and biochemical improvement, 28 hours after therapy was initiated he was found to have profound hypocalcemia (2.6 meq/liter), hypomagnesemia (0.8 meq/liter) and hyperphosphatemia (9.2 mg/dl). All three electrolyte levels had been normal upon admission, and they were gradually corrected with appropriate supplementation of calcium and magnesium and discontinuation of the intravenous phosphate. We interpret these iatrogenic electrolyte abnormalities in the patient described to have been the result of the massive phosphate load administered, resulting not only in hypocalcemia, but also in hypomagnesemia that inhibited parathyroid hormone release.Current recommendations suggest replacement of the potassium losses in diabetic ketoacidosis with the phosphate salt to compensate for depleted stores of 2,3-diphosphoglycerate. We caution physicians that such a regimen can result in severe electrolyte disturbances which potentially may be life threatening. Judicious use of potassium phosphate as an adjunct to traditional potassium chloride therapy, and close monitoring of serum calcium, magnesium and phosphorus, appears to be a preferable therapeutic regimen than potassium phosphate alone.     

Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.

The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents.