Prognostic value of a new electrocardiographic method for diagnosis of left ventricular hypertrophy in essential hypertension.

OBJECTIVES: We tested the prognostic value of a new electrocardiographic (ECG) method (Perugia score) for diagnosis of left ventricular hypertrophy (LVH) in essential hypertension and compared it with five standard methods (Cornell voltage, Framingham criterion, Romhilt-Estes point score, left ventricular strain, Sokolow-Lyon voltage). BACKGROUND: Several standard ECG methods for assessment of LVH are used in the clinical setting, but a comparative prognostic assessment is lacking. METHODS: A total of 1,717 white hypertensive subjects (mean age 52 years; 51% men) were prospectively followed up for up to 10 years (mean 3.3). RESULTS: At entry, the prevalence of LVH was 17.8% (Perugia score), 9.1% (Cornell), 3.9% (Framingham), 5.2% (Romhilt-Estes), 6.4% (strain) and 13.1% (Sokolow-Lyon). During follow-up there were 159 major cardiovascular morbid events (33 fatal). The event rate was higher in the subjects with than in those without LVH (all p < 0.001) according to all methods except the Sokolow-Lyon method. By multivariate analysis, an independent association between LVH and cardiovascular disease risk was maintained by the Perugia score (hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.5 to 2.8) and the Framingham (HR 1.91, 95% CI 1.1 to 3.2), Romhilt-Estes (HR 2.63, 95% CI 1.7 to 4.1) and strain methods (HR 2.11, 95% CI 1.4 to 3.2). The Perugia score showed the highest population-attributable risk for cardiovascular events, accounting for 15.6% of all cases, whereas the Framingham, Romhilt-Estes and strain methods accounted for 3.0%, 7.4% and 6.8% of all events, respectively. LVH diagnosed by the Perugia score was also associated with an increased risk of cardiovascular mortality (HR 4.21, 95% CI 2.1 to 8.7), with a population-attributable risk of 37.0%. CONCLUSIONS: The Perugia score carried the highest population-attributable risk for cardiovascular morbidity and mortality compared with classic methods for detection of LVH. Traditional interpretation of standard electrocardiography maintains an important role for cardiovascular risk stratification in essential hypertension.

Prognostic significance of serial changes in left ventricular mass in essential hypertension.

BACKGROUND: Increased left ventricular (LV) mass predicts an adverse outcome in patients with essential hypertension. The purpose of this study was to determine the relation between changes in LV mass during antihypertensive treatment and subsequent prognosis. METHODS AND RESULTS: Procedures including echocardiography and 24-hour ambulatory blood pressure (BP) monitoring were performed in 430 patients with essential hypertension before therapy and after 1217 patient-years. Months or years after the follow-up visit, 31 patients suffered a first cardiovascular morbid event. The patients with a decrease in LV mass from the baseline to follow-up visit were compared with those with an increase in LV mass. There were 15 events (1.78 per 100 person-years) in the group with a decrease in LV mass and 16 events (3.03 per 100 person-years) in the group with an increase in LV mass (P=.029). In a Cox model, the lesser cardiovascular risk in the group with a decrease in LV mass (hazard ratio [HR], 0.46; 95% CI, 0.22 to 0.99) remained significant (P=.04) after adjustment for age (HR, 1.06; 95% CI, 1.03 to 1.10; P=.0008) and baseline LVH at ECG (HR, 3.85; 95% CI, 1.52 to 9.78; P=.012). In that model, baseline LV mass bordered on statistical significance (HR, 1.01; 95% CI, 1.00 to 1.03; P=.06). In the subset with LV mass > 125 g/m2 at the baseline visit (26% of subjects), the event rate was lower among the subjects who achieved regression of LVH than in those who did not (1.58 versus 6.27 events per 100 person-years; P=.002). This difference held in the multivariate analysis (HR, 0.18; 95% CI, 0.05 to 0.68). CONCLUSIONS: In essential hypertension, a reduction in LV mass during treatment is a favorable prognostic marker that predicts a lesser risk for subsequent cardiovascular morbid events. Such an association is independent of baseline LV mass, baseline clinic and ambulatory BP, and degree of BP reduction.

Comparison of target organ damage in renovascular and essential hypertension.

In many reports, the prevalence of target organ damage in renovascular hypertension (RVH) appears to be higher than in essential hypertension (EH). Since in most studies the renal artery stenosis is part of a diffuse atherosclerotic disease, it is not known whether these complications are due to RVH itself or to the vascular disease. We have undertaken a case control study of 92 patients divided into two groups (46 in each), one with RVH and the other with EH and abdominal aortic aneurysm, with a comparable degree of diffuse atherosclerotic vascular disease. The vascular state of the extracranial carotid arteries and abdominal and inferior limb districts was investigated with angiography and sonography. The prevalence of left ventricular hypertrophy (LVH) and ischemic heart disease (IHD) were assessed by electrocardiography. Serum creatinine and urinary protein excretion were employed in the renal evaluation. While the analysis of the results confirmed an even diffusion of atherosclerotic vascular disease between the two groups, a significant difference was found in the prevalence of heart and renal damage. LVH was present in 32.6% of RVH patients versus 10.8% in EH (P = .02). Serum creatinine > 1.4 mg/dL was found in 50% of RVH and in 23.9% of EH, (P = .01). The prevalence of proteinuria in RVH was also higher although not reaching the statistical significance. The results suggest that, in patients with comparable degrees of atherosclerotic vascular disease, RVH is responsible for the higher prevalence of target organ damage in this condition compared to those with EH.

Association between persistent pressure overload and ventricular arrhythmias in essential hypertension.

Hypertension is a risk factor for sudden cardiac death, and some data indicate that frequent and complex ventricular arrhythmias may be additional risk markers in hypertensive individuals. We investigated the relation between ventricular arrhythmias and the persistence of increased blood pressure levels over 24 hours in subjects with essential hypertension. We studied 126 never-treated subjects with essential hypertension (83 men) who underwent 24-hour electrocardiographic monitoring, 24-hour ambulatory blood pressure monitoring, and echocardiography. Premature ventricular beats were detected in 71% of the subjects. Compared with subjects in Lown class 0-1, subjects with frequent or complex ventricular arrhythmias (Lown class > or = 2) were older (54 versus 45 years) and had a longer duration of hypertension (5.4 versus 2.8 years), a greater left ventricular mass (147 versus 127 g.m-2), and a blunted nocturnal reduction in ambulatory blood pressure (7%/12% versus 12%/16%). The number of premature ventricular beats over 24 hours was associated with age (r = .25), left ventricular mass (r = .24), and pulse pressure (r = .18) and inversely associated with the present reduction in blood pressure from day to night (r = -.29 for systolic and -.25 for diastolic pressures). In a multiple logistic regression analysis, frequent or complex ventricular arrhythmias (Lown class > or = 2) were predicted by an age > or = 60 years (odds ratio, 10.4 95% confidence interval, 2.4-44.8), left ventricular hypertrophy at echocardiography (odds ratio, 4.2; 95% confidence interval, 1.5-11.6), and a < 10% reduction in blood pressure from day to night ("nondipping" pattern; odds ratio, 2.9;95% confidence interval, 1.2-7.0). We conclude that in addition to the strong effect of age and left ventricular hypertrophy at echocardiography, the persistence of high blood pressure levels over the 24 hours ("nondipping" pattern) is an independent predictor of the frequency and complexity of ventricular arrhythmias in never treated subjects with essential hypertension.

Prognostic value of left ventricular mass and geometry in systemic hypertension with left ventricular hypertrophy.

To determine the independent prognostic significance of left ventricular (LV) mass and geometry (concentric vs eccentric pattern) in hypertensive subjects with LV hypertrophy at echocardiography, 274 subjects were followed for up to 8.7 years (mean 3.2). All patients had systemic hypertension and LV mass > or = 125 g/body surface area (BSA) and underwent ambulatory blood pressure (BP) monitoring and echocardiography before treatment. Eccentric and concentric hypertrophy were defined by the ratio between LV posterior wall thickness and LV radius at telediastole <0.45 and > or = 0.45, respectively. Age, sex ratio, body mass index, office BP and serum glucose, cholesterol, and triglycerides did not differ between the groups with eccentric (n=145) and concentric (n=129) hypertrophy. Average 24-hour daytime, and nighttime systolic ambulatory BPs were higher in concentric than in eccentric hypertrophy (all p <0.01). LV mass was slightly greater in concentric than in eccentric hypertrophy (157 vs 149 g/BSA, p <0.05). Endocardial and midwall shortening fraction were lower in concentric than in eccentric hypertrophy (96.5% vs 106.0% of predicted and 71.4% vs 89.7% of predicted, respectively; both p <0.01). The rate of major cardiovascular morbid events was 2.20 and 3.34 per 100 patient-years in eccentric and concentric hypertrophy, respectively (log rank test, p=NS). Age >60 and LV mass above median (145 g/BSA) were significant adverse prognostic predictors, while LV geometry (eccentric vs concentric hypertrophy) and ambulatory BP were not. The event rates per 100 patient-years were 1.38 and 3.98, respectively, in the patients with LV mass below and above median (age-adjusted relative risk 2.70; 95% confidence interval [CI] 1.03 to 6.63; p=0.015). In hypertensive subjects with established LV hypertrophy, LV mass, but not its geometric pattern, provides important prognostic information independent of conventional risk markers including office and ambulatory BP.

Cigarette smoking, ambulatory blood pressure and cardiac hypertrophy in essential hypertension.

OBJECTIVE: To assess the role of blood pressure in the association between cigarette smoking and left ventricular mass in male and female subjects with essential hypertension. DESIGN: A case-control study with matching ratio of 1:4. PATIENTS AND METHODS: We studied 115 heavy smokers (> or = 20 cigarettes/day; 91 men) and 460 non-smokers (364 men) with essential hypertension. Subjects were matched by sex, age (within 5 years) and clinic systolic and diastolic blood pressures (within 5 mmHg). All the subjects underwent 24 h off-therapy non-invasive ambulatory blood pressure monitoring and echocardiography. RESULTS: By matching, clinic blood pressure was nearly identical in smokers and non-smokers (158/99 versus 158/98 mmHg). Daytime ambulatory blood pressure was significantly higher in the smokers than in the non-smokers (150/97 versus 143/93 mmHg), whereas night-time blood pressure did not differ between the two groups (129/79 versus 126/78 mmHg). Smokers had a higher 24 h but not clinic heart rate. Variability of systolic and diastolic blood pressure was slightly greater in smokers when expressed in terms of the standard deviation of the 24 h average (15.9/13.0 versus 14.6/12.2 mmHg), but not after correction for average blood pressure. Left ventricular mass was greater in the smokers than in the non-smokers (119 versus 110 g/m2), and this difference remained after adjustment for clinic blood pressure and other related covariates. However, when clinic blood pressure was replaced by daytime ambulatory blood pressure in the equation, adjusted values of left ventricular mass did not differ between the smokers and the non-smokers (113 versus 112 g/m2). CONCLUSION: In patients with essential hypertension, heavy cigarette smoking (> or = 20 cigarettes/day) is associated with a definite increase in left ventricular mass through a rise in whole-day blood pressure. A pressor mechanism of that type may not be detected by the standard measurement of blood pressure in the clinic, which would make ambulatory blood pressure monitoring a valuable diagnostic tool in this setting.

White coat hypertension and white coat effect. Similarities and differences.

The rise in blood pressure (BP) associated with clinical visit (white coat effect) may be one basic mechanism of white coat hypertension (persistently raised clinic BP together with a normal BP outside the clinic), but the relations between white coat hypertension, white coat effect, and target organ damage have not yet been assessed on large populations. Thus, we performed 24-h noninvasive ambulatory BP monitoring and 2D-guided M-mode echocardiography in 1,333 untreated subjects with essential hypertension and 178 control normotensive subjects. White coat hypertension was defined by an average daytime ambulatory BP < 131/86 mm Hg in women and < 136/87 mm Hg in men and its prevalence was 18.9% (n = 252). The white coat effect was calculated for systolic and diastolic BP as the difference between clinic BP and average daytime ambulatory BP. Echocardiographic left ventricular mass was slightly but not significantly greater in the group with white coat hypertension than in the normotensive group (93 v 87 g/m2, P = NS), and increased in the group with ambulatory hypertension (112 g/m2, P < .01). The prevalence of white coat hypertension markedly decreased from the first to the fourth Joint National Committee V (JNC V) stage of severity of hypertension (186/559 subjects (33%) in I; 59/501 (11%) in II; 7/230 (3%) in III; 0/43 (0%) in IV; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension.

To determine the prognostic significance of ambulatory blood pressure, we prospectively followed for up to 7.5 years (mean, 3.2) 1187 subjects with essential hypertension and 205 healthy normotensive control subjects who had baseline off-therapy 24-hour noninvasive ambulatory blood pressure monitoring. Prevalence of white coat hypertension, defined by an average daytime ambulatory blood pressure lower than 131/86 mm Hg in women and 136/87 mm Hg in men in clinically hypertensive subjects, was 19.2%. Cardiovascular morbidity, expressed as the number of combined fatal and nonfatal cardiovascular events per 100 patient-years, was 0.47 in the normotensive group, 0.49 in the white coat hypertension group, 1.79 in dippers with ambulatory hypertension, and 4.99 in nondippers with ambulatory hypertension. After adjustment for traditional risk markers for cardiovascular disease, morbidity did not differ between the normotensive and white coat hypertension groups (P = .83). Compared with the white coat hypertension group, cardiovascular morbidity increased in ambulatory hypertension in dippers (relative risk, 3.70; 95% confidence interval, 1.13 to 12.5), with a further increase of morbidity in nondippers (relative risk, 6.26; 95% confidence interval, 1.92 to 20.32). After adjustment for age, sex, diabetes, and echocardiographic left ventricular hypertrophy (relative risk versus subjects with normal left ventricular mass, 1.82; 95% confidence interval, 1.02 to 3.22), cardiovascular morbidity in ambulatory hypertension was higher (P = .0002) in nondippers than in dippers in women (relative risk, 6.79; 95% confidence interval, 2.45 to 18.82) but not in men (P = .91). Our findings suggest that ambulatory blood pressures stratifies cardiovascular risk in essential hypertension independent of clinic blood pressure and other traditional risk markers including echocardiographic left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved electrocardiographic diagnosis of left ventricular hypertrophy.

This study was aimed at improving the performance of standard electrocardiographic criteria of left ventricular hypertrophy (LVH) in essential hypertension using echocardiographic left ventricular mass as reference. In 923 white, untreated hypertensive subjects (mean age 51, prevalence of echocardiographic LVH 34%), sensitivity of electrocardiographic criteria of LVH varied between 9% and 33% and specificity was generally > or = 90%. The sum of Sv3 + RaVL (Cornell voltage) showed the closest association with echocardiographic left ventricular mass (r = 0.48, p < 0.001), and its performance was superior to that of Sokolow-Lyon voltage in a receiver-operating characteristic curve analysis. A modified partition value of the Cornell voltage was tested (> 2.4 mV in men and > 2.0 mV in women), that yielded a good combination between sensitivity (26% in men and 19% in women, overall 22%) and specificity (96% in men and 95% in women, overall 95%). When LVH at electrocardiography was defined as the positivity of at least 1 of the following 3 criteria--Sv3 + RaVL > 2.4 mV in men or > 2.0 mV in women, a typical strain pattern, or a Romhilt-Estes point score > or = 5--sensitivity increased to 39% in men and 29% in women (overall 34%) and specificity decreased to 94% in men and 93% in women (overall 93%). Sensitivity of electrocardiography progressively increased from the first to the fourth quartile of left ventricular mass in subjects with echocardiographic LVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymmetric left ventricular remodeling due to isolated septal thickening in patients with systemic hypertension and normal left ventricular masses.

Early identification of left ventricular (LV) structural changes may have an impact on the outlook of patients with essential hypertension. Of 669 untreated hypertensive subjects, 496 (74%) with normal LV mass at echocardiography (< 125 g/m2) were grouped according to normal LV geometry (n = 303; 61%), asymmetric LV remodeling due to isolated septal thickening (n = 111; 22%), asymmetric LV remodeling due to isolated posterior wall thickening (n = 5; 1%), or concentric LV remodeling due to septal and posterior wall thickening (n = 77; 16%). Remodeling was defined as twice the thickness of septum or posterior wall divided by the internal diameter at end diastole > 0.45. Twenty-four-hour noninvasive ambulatory blood pressure (BP) monitoring was performed in all subjects. Compared with subjects with normal LV geometry, those with asymmetric LV remodeling due to isolated septal thickening showed increased clinic BP (158/100 vs 153/97 mm Hg, both p < 0.05), mean daytime ambulatory BP (144/95 vs 138/90 mm Hg, both p < 0.01), mean nighttime ambulatory BP (128/80 vs 122/76 mm Hg, both p < 0.01), LV mass (99 vs 89 g/m2, p < 0.001), total peripheral resistance (1,881 vs 1,562 dynes s cm-5, p < 0.01) and known duration of hypertension (5.5 vs 3.6 years, p < 0.01) and decreased stroke index (39 vs 47 ml/m2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive ambulatory BP monitoring during the night: randomised comparison of different reading intervals.

Frequent measurements of BP during noninvasive monitoring could interfere with sleep, with consequent possible overestimation of nocturnal BP. We performed 24h noninvasive ambulatory BP monitoring (Space-Labs 90207) in 24 patients with essential hypertension twice, 1 week apart. Subjects were instructed to follow, as far as possible, a similar pattern of daily activity during the two sessions. The frequency of daytime readings (from 06.00 to 22.00 h) was kept constant in the two sessions (one every 15 minutes), while that of nocturnal readings (from 22.00 to 06.00 h) varied in random order: every 15 minutes in session A and every 60 minutes in session B. Mean sleep BP did not differ between session A (138/83 mmHg (SD 15/10 mmHg)) and session B (138/83 mmHg (SD 14/10 mmHg)). The percentage reduction of ambulatory SBP and DBP from wake to sleep was 9.7% and 10.0%, respectively, in session A, and 14.0% and 14.1%, respectively, in session B (all P = NS). The duration of sleep was 6.1 hours (SD 2 hours) in session A and 6.0 hours (SD 2 hours) in session B (P = NS). On average, 6.8% of nocturnal readings in session A and 7.6% of nocturnal readings in session B failed to pass the automatic editing criteria, but no hourly interval was lacking in valid measurements on both sessions.(ABSTRACT TRUNCATED AT 250 WORDS)

Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events.

BACKGROUND: In essential hypertension, a blunted or absent nocturnal fall in blood pressure (BP) may be associated with increased target organ damage. In this case-control study, we tested the hypothesis that an association exists between a blunted or absent nocturnal fall in BP and future cardiovascular morbid events in patients with essential hypertension. METHODS AND RESULTS: Case subjects were 32 hypertensive patients with a first fatal or nonfatal major cardiovascular event who had off-therapy ambulatory BP monitoring 1 to 5 years earlier in the context of a registry of morbidity and mortality in hypertensive patients. Control subjects were 49 hypertensive patients free from cardiovascular events. The groups were matched with regard to date of baseline ambulatory BP monitoring, age, sex, clinic systolic and diastolic BP, and daytime ambulatory systolic and diastolic BP. At their baseline evaluation, cases and controls did not differ, in either sex, with respect to clinic BP (men, 164/100 vs 162/99 mmHg; women, 178/96 vs 180/93 mmHg), mean daytime ambulatory BP (men, 151/94 vs 147/95 mm Hg; women, 156/90 vs 158/89 mm Hg), age (men, 55 vs 56 years; women, 69 vs 68 years), sex, body weight, serum cholesterol, known duration and family history of hypertension, smoking habits, renal function, or prevalence of diabetes. Echocardiographic left ventricular mass, determined in a subset of patients, was greater in cases than in controls in men (145 vs 115 g/m2, P = .038) and women (137 vs 102 g/m2, P = .032). The time interval between baseline ambulatory BP monitoring and subsequent cardiovascular event (cases: mean, 2.1 years) or last contact with our center (controls: mean, 2.5 years) did not differ between the groups. In the baseline ambulatory BP profile, the nocturnal reductions of systolic and diastolic BP in men were 9% and 11%, respectively, in cases vs 9% and 12% in controls (all P = NS), whereas in women they were 3% and 8% in cases vs 11% and 16% in controls (P = .002/.004). CONCLUSIONS: This retrospective case-control study suggests an association between the reduction or absence of the usual nocturnal fall in BP and future cardiovascular morbid events in white women with essential hypertension.

Variability between current definitions of 'normal' ambulatory blood pressure. Implications in the assessment of white coat hypertension.

The assessment of white coat hypertension is complicated by the lack of generally agreed-on normal limits of ambulatory blood pressure. To assess the influence of four of these limits on the prevalence of white coat hypertension and the corresponding distribution of left ventricular hypertrophy, we performed 24-hour ambulatory blood pressure monitoring and echocardiographic studies in 346 untreated patients with essential hypertension and 47 age-matched normotensive control subjects. The upper limits of normal daytime ambulatory blood pressure were lower using standards drawn from clinically normotensive populations than using standards drawn, partly or entirely, from general populations. The prevalence of white coat hypertension differed markedly using the different standards, being 12.1%, 16.5%, 28.9%, and 53.2% (chi 2 = 346.0, p less than 0.0001). Left ventricular mass index averaged 77 g/m2 in the control group, 85 g/m2 in the two groups with white coat hypertension defined by using standards drawn from normotensive populations (both comparisons not significant versus control group), and 90 and 98 g/m2 in the two groups with white coat hypertension defined by using the other two standards (both p less than 0.01 versus control group). The prevalence of echocardiographic left ventricular hypertrophy was 0% in the control group, 2.4% and 3.5% in the two groups with white coat hypertension defined by using standards drawn from normotensive populations, and 9.0% and 14.7% in the other two groups with white coat hypertension (p less than 0.05 and p less than 0.01, respectively, versus control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired renal functional reserve and albuminuria in essential hypertension.

The stimulatory effects of an infusion of amino acids on glomerular filtration rate has previously been used to measure renal functional reserve and detect glomerular hyperfiltration. Thirty four patients with mild to moderate essential hypertension and seemingly normal renal function and 22 healthy controls were given infusions of amino acids to investigate whether renal functional reserve is reduced in essential hypertension and to detect patients at risk of renal damage. Although basal creatinine clearance increased after the infusion of amino acids in the controls (mean 27.9 ml/min; 95% confidence interval 18.2 to 37.6), the overall change was lower in the patients (mean 13.4 ml/min; 8.3 to 18.5), 11 of the 34 showing no increase at all. In these 11 non-responders the mean systolic blood pressure was higher than that in the 23 others (178.5 mmHg v 157 mmHg, respectively). Mean urinary albumin excretion was abnormal in the patients (93.3 mg/24 h; 44.2 to 142.4); eight of the 11 non-responders had an albumin excretion above the normal range (greater than 20 mg/24 h). In the 11 patients without renal functional reserve a positive correlation was found between basal creatinine clearance and albumin excretion (r = 0.695). As consumed renal reserve and albuminuria are markers of glomerular hyperfiltration studying renal function before and after infusion of amino acids can detect hypertensive patients at risk of progressive renal damage.

Circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease. Their relationship to immune function.

Complement-fixing and non-complement-fixing circulating immune complexes were determined in 42 previously untreated Hodgkin's disease patients by Pl.A.T., C1qB-ELISA and KgB tests. The functional status of the monocyte-macrophage system was evaluated by measuring the serum lysozyme levels. These parameters were then correlated with the patient's immunocompetence, as assessed by the percentage of E-rosette forming cells and the PHA response. The Pl.A.T. was positive in 35.7% patients, the KgB-test in 34.3% and the C1qB-ELISA in 19%. There was overlapping of positive results in 37.5% patients. No correlation was found between CIC levels and stage, unfavourable histology or B symptoms. The PHA response was significantly depressed in CIC + patients, as detected by the C1qB-ELISA technique (p less than 0.0025). The data on serum lysozyme offer an insight into the possible mechanism regulating serum levels of CICs in Hodgkin's disease. Two distinct situations seem to exist: in the first, high CIC levels are associated with normal or low serum lysozyme values (p versus normal controls: n.s.); in the second, serum lysozyme levels are high and CIC absent (p less than 0.005 versus control values). The lowest lysozyme levels are also associated with a depressed lymphocyte PHA response. It could, therefore, be concluded that, in Hodgkin's disease, the presence, or absence, of CICs is directly correlated to the degree of monocyte-macrophage clearance activity and that the host's immunocompetence plays an important role in the induction and/or maintenance of this functional defect.

The in vivo effect of thymic factor (thymostimulin) administration on circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease patients.

The in vivo effect of a calf thymus extract, thymostimulin, on the levels of circulating immune complexes (CIC) and serum lysozyme was evaluated in 32 patients with untreated Hodgkin's disease. Using the platelet aggregation test for detecting CICs, 12 patients (37%) had positive titers before thymostimulin treatment; 3 patients (10%) remained positive following therapy. Serum levels of Clq-binding immune complexes were evaluated (greater than 24.5 micrograms/ml) in 8 patients prior to thymostimulin therapy (mean value: 42.3 micrograms/ml); 3 patients continued to have elevated levels after treatment. Serum lysozyme levels for Hodgkin's patients was similar to control values (10.6 vs. 8.3 micrograms/ml); however, the Hodgkin's patients with initially elevated CICs had a lower serum lysozyme level than patients with initially normal CICs (12.9 vs. 7.3, p less than 0.02). Thymostimulin increased serum lysozyme levels in the Hodgkin's patients in whom the CICs were initially elevated (7.3 vs. 10.4 micrograms/ml, p less than 0.05). These data suggest that thymostimulin exerts an effect on the nonspecific immune system of Hodgkin's disease patients.

Stimulation of polymorphonuclear leukocyte chemotaxis by cold precipitable complexes containing DNA-anti-DNA in active nephritis of systemic lupus erythematosus.

DNA-anti-DNA cold precipitable complexes (CPC) isolated from 21 patients with systemic lupus erythematosus were tested for their ability to stimulate polymorphonuclear leukocyte (PMN) chemotaxis and to activate complement in vitro. The complexes activated complement in 20 out of 21 cases and stimulated PMN chemotaxis in 13 out of 21. The stimulation of chemotaxis was present in the majority of patients with renal involvement (10 out of 13) and active disease (8 out of 9), while being almost negligible in those without renal involvement or active disease. In patients studied sequentially, CPC-stimulated chemotaxis was reduced to nil with the remission of the disease. CPC appears to play a pathogenic role in active systemic lupus erythematosus with renal involvement.