Walter Panarelli

Baseline Sodium-Lithium Countertransport and 6-Year Incidence of Hypertension The Gubbio Population Study

BACKGROUND Sodium-lithium countertransport (Na-Li CT) activity is high in persons with hypertension. This study investigated whether high Na-Li CT relates to development of hypertension. METHODS AND RESULTS At the baseline visit of the Gubbio Population Study, 4210 people of the 5376 surveyed were 18 to 74 years old; of these, 1599 were hypertensive (systolic pressure > or = 140 mm Hg, or diastolic pressure > or = 90 mm Hg, or on antihypertensive drug therapy). Of the 2611 nonhypertensives, 302 did not have Na-Li CT measured and 580 did not participate in 6-year follow-up. This analysis, therefore, deals with data collected on 1729 men 18 to 74 years old and women 18 to 74 years old who at baseline were nonhypertensive and had Na-Li CT measurement. Compared with individuals who were nonhypertensive at baseline and follow-up, individuals with incident hypertension at follow-up (systolic pressure > or = 140 mm Hg, or diastolic pressure > or = 90 mm Hg, or on antihypertensive drug therapy) had higher baseline values of Na-Li CT, blood pressure, age, body mass index, plasma cholesterol, and alcohol intake (P < .05). Baseline Na-Li CT was positively associated (P < .05) with development of hypertension in quartile analysis, with highest incidence of hypertension among men and women with Na-Li CT in the highest quartile (for men, > or = 376 and for women, > or = 311 mumol Li-L red blood cells-1.h-1). In univariate logistic regression, incidence of hypertension was related to baseline value of Na-Li CT, blood pressure, age, body mass index, plasma cholesterol, and alcohol intake (P < .05). In multiple logistic regression analysis, individuals with baseline Na-Li CT higher by 127 mumol (pooled SD for men and women) had 1.23 times greater risk of incident hypertension with control for sex and baseline age, body mass index, systolic pressure, and other confounders (P < .001). CONCLUSIONS Na-Li CT is a predictor of hypertension risk in adults.

Serum uric acid for short-term prediction of cardiovascular disease incidence in the Gubbio population Study.

Objective — The Gubbio Study is an Italian population study measuring risk factors for and incidence of major cardiovascular diseases.This analysis investigates the association of serum uric acid with the incidence of coronary and cardiovascular events. Methods — A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom serum uric acid was measured in 1983 along with other standard risk factors, were followed up for 6 years and the incidence of coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events, both fatal and non-fatal, was computed. Proportional hazards models were used for the prediction of these events. Results — In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific quintiles (Q) of serum uric acid with 428 ± 76 (Q5) and 198 ± 42 (Q1) μmol/l, respectively. Although higher rates were seen in Q5 as compared to Q1 for all three first event categories considered (relative risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8 other risk factors, serum uric acid showed a statistically significant contribution to predict CVD incidence [relative risk (RR) for 92 μmol/l difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45], whereas the statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98-1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant. Diuretic treatment and blood urea, as further confounders, were positively and significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum uric acid maintained its independent and statistically significant role in the prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific treatments to lower serum uric acid levels (in 1.13% of the population), tested as final confounders, was not statistically contributory. Conclusions — Increased serum uric acid levels are independently and significantly associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of serum uric acid can be properly assessed to explain CHD incidence.

Is there a relationship between left ventricular mass and plasma glucose and lipids independent of body mass index? Results of the Gubbio Study.

BACKGROUND AND AIMS The association between left ventricular (LV) mass (M) and variables described as features of the insulin resistance syndrome, such as obesity and measures o lipid and carbohydrate metabolisms, has been reported in hypertensives. The aim of the present study was to investigate in a large, population based group of non hypertensive people, the prevalence of LV hypertrophy (H) and the relationship of LVM with some of the variables described in the insulin resistance syndrome, independently of obesity. For this reason we investigated the normotensive subjects in the age range 45-54 yrs (n = 435) of the total population of participants in the Gubbio Population Study. METHODS AND RESULTS Serum lipids, cholesterol (Chol), triglyceride (Tg), HDL cholesterol, fasting blood glucose (FBG), blood pressure (BP), body weight and height were measured and body mass index (BMI) was calculated; LVM was assessed by M-mode echocardiography. Using a normalization criterion not related to body weight (g/m2.7) and the cut-off of 49.2 g/m2.7 for men and 46.7 g/m2.7 for women, LVH was found in 25% of the sample whilst, when LVM was corrected by body surface area (cut-off 116 g/m2 for men and 104 g/m2 for women), the prevalence of LVH was quite lower (10.3%). In the univariate analyses LVMi was closely related to BP, BMI and metabolic variables whilst in the multivariate analysis only BP, BMI, and age were detected as independent predictors of LVMi. When the sample was divided into obese and non-obese subjects on the basis of BMI (cut-off 30 kg/m2), no difference in metabolic variables was seen between subjects with and without LVH within each BMI class. Regarding left ventricular geometry, RWT was positively related to triglycerides and blood glucose and inversely to HDL-chol. CONCLUSIONS The present study in the middle age normotensive sample of the general population of Gubbio extends to normotensives the relationship between left ventricular mass and metabolic parameters already seen in hypertensives. BMI seems to account for most of the increases in LVM since the prevalence of LVH, which was definitely high when LVM was not normalized to body weight, fell to approximately 4% when the influence of body weight was excluded. Moreover differences in metabolic values between subjects with and without LVH disappeared when the subjects were stratified by BMI. Left ventricular geometry, on the other hand, seems to be related to some metabolic variables.

Red blood cell count in short-term prediction of cardiovascular disease incidence in the Gubbio population study.

Objective — The Gubbio Study is an Italian population study measuring risk factors and incidence for major cardiovascular diseases. This analysis investigates the association between red blood cell (RBC) count, after preliminarily taking into account haematocrit, and incidence of coronary and cardiovascular events. Methods — A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom RBC count and haematocrit were measured in 1983 along with other standard risk factors, were followed up for 6 years and incidence was estimated for both fatal and non-fatal coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events. Proportional hazards models were solved for the prediction of these events. Results — In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Preliminarily, both haematocrit and RBC count, two highly correlated variables, were studied to predict CVD events; however, haematocrit did not contribute multivariately, in the overall population and separately in men and women.Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific RBC count quintiles (Q) and a difference was observed between Q5 and Q1 (with 5.21 ± 0.31 and 4.18 ± 0.23 x 106 per ml, respectively) for CHD any criterion (p < 0.07) and CVD (p < 0.05). P on trends was < 0.05 for both end-points. In multivariate models, adjusted for 7 other risk factors, RBC count contributed a weak statistical significance to predict CVD incidence [relative risk (RR) for a 0.5 x 106 per ml difference 1.23 with 95% confidence intervals (CI) 1.00-1.51], whereas its contribution to predict CHD any criterion (RR = 1.19 with CI 0.93-1.51) and CHD hard criteria (RR = 1.15 with CI 0.83-1.58) was not statistically significant. Inclusion of blood glucose and presence of diuretics (11.33% of the population) as possible confounders had no major effect although the latter were, as expected, a significant risk factor (RR = 1.90 with CI 1.28-2.82) which further diluted the CVD predictive role of RBC count (RR = 1.22 with CI 0.99-1.50). Conclusions — Increased RBC count is independently (yet weakly) associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of RBC count can be properly assessed to explain CHD incidence.

Sodium-Lithium Countertransport and Blood Pressure Change Over Time The Gubbio Study

Sodium-lithium countertransport activity in red blood cells relates to blood pressure (BP) and the prevalence of hypertension. This study investigated in adults the relation of sodium-lithium (Na-Li) countertransport to BP change from baseline to 6-year follow-up. In the Gubbio Population Study, 4210 men and women were 18 to 74 years old at baseline (1983-1986), and 3766 had a valid baseline Na-Li countertransport measurement; of these, 2729 were reexamined at 6 years of follow-up (1989-1992) and made up the study cohort. At baseline, data collection included age, height, weight, BP, pulse rate, drug treatment, alcohol intake, ratio of sodium to potassium in spot urine, plasma cholesterol, and Na-Li countertransport in red blood cells. At 6-year follow-up, data for age, BP, and drug treatment were collected as at baseline. From baseline, average BP declined for people on antihypertensive medication at follow-up and for those with baseline BP greater than or equal to 140/90 mm Hg (systolic/diastolic) and did not change or increased for the remaining participants. In quartile and correlation analyses controlled for sex, baseline BP, and antihypertensive treatment, BP change related significantly and directly to baseline Na-Li countertransport. In multiple linear regression analyses done for the entire cohort with control for other confounders, the regression coefficient of baseline Na-Li countertransport to BP change over time was positive and borderline significant. The Na-Li countertransport coefficient was positive and significant when analyses were done with the use of a categorical value of baseline Na-Li countertransport (quartile 4 and quartiles 1 through 3 combined). In both models, the Na-Li countertransport coefficient was the strongest for people with baseline BP greater than or equal to 120/80 mm Hg or for people with baseline age of 45 years or older. In conclusion, Na-Li countertransport significantly relates to BP change over time in adults.

Twenty-year cardiovascular and all-cause mortality trends and changes in cardiovascular risk factors in Gubbio, Italy: the role of blood pressure changes.

Aims In an observational population study that lasted 20 years, the relationships between mortality trends and changes in cardiovascular risk factor levels were examined. Methods and results In the town of Gubbio, in central Italy, population surveys for measurement of cardiovascular risk factors were performed 20 years apart. In a subset of the initial cohort (1927 men and 2333 women), mortality data were collected for 20 years. Cardiovascular risk factor levels were compared in individuals in the same age range (20–79 years) examined at the initial survey (1927 men and 2333 women) and at the final survey (1761 men and 2055 women). Age-adjusted rates significantly declined, by 28% among men and 51% among women, for all causes of death, and by 50% among men and 71% among women for cardiovascular disease deaths. Declines were observed in the levels of systolic blood pressure, serum cholesterol, resting heart rate, smoking habits, BMI, plasma glucose (the latter two only in women) and the estimated cardiovascular risk, together with increases in serum high-density lipoprotein cholesterol and in the proportion of treated and controlled hypertensive patients. Conclusion Although similar but less impressive changes were recorded in Italy at large, the existence of the observational study in Gubbio might have motivated the general population and the medical profession towards actions promoting general health.

Relationship between plasma insulin and left ventricular mass in normotensive participants of the Gubbio Study

background There is substantial but not conclusive evidence that insulin resistance is related to left ventricular mass (LVM) in hypertensive individuals. To what extent this association is mediated by the relationship between plasma insulin and body size and build is still debated, and is poorly explored in nonhypertensive people.

Prospective analysis of traits related to 6-year change in sodium-lithium countertransport

Sodium-lithium countertransport (Na-Li CT) activity in red blood cells relates cross-sectionally and longitudinally to blood pressure and hypertension. Lifestyle and metabolic factors relate cross-sectionally to this sodium transporter. The aim of this study was to conduct a prospective analysis of 6-year Na-Li CT change and of traits related to Na-Li CT change. In 2183 participants in the Gubbio Population Study (972 men and 1211 women; baseline ages, 18 to 74 years), the following data collected at baseline and 6-year follow-up were analyzed: Na-Li CT; gender; age; body mass index (BMI); blood pressure; antihypertensive treatment; alcohol intake; smoking habits; urinary sodium-to-potassium ratio; and plasma cholesterol, glucose, uric acid, sodium, potassium, and triglycerides (measured only at follow-up). Six-year changes were defined as follow-up minus baseline values. Na-Li CT was higher at follow-up than at baseline in both genders (P<0.001). Baseline Na-Li CT; baseline and change values of BMI; and change values of alcohol intake, plasma potassium, and plasma glucose related to Na-Li CT change significantly and independently with control for other variables. Follow-up plasma triglyceride levels also related independently to Na-Li CT change. Coefficients were positive for BMI, alcohol intake, and plasma glucose and triglyceride levels and were negative for baseline Na-Li CT and plasma potassium levels. Baseline and change values of other variables did not relate significantly to Na-Li CT change. In conclusion, in prospective analyses, BMI, alcohol intake, plasma glucose, and lipids were directly related to Na-Li CT change; baseline Na-Li CT and plasma potassium levels were inversely related. The data support the concept that lifestyle and related metabolic factors influence Na-Li CT.