BackgroundIschaemic heart disease is a global priority of health-care policy, because of its social repercussions and its impact on the health-care system. Yet there is little information on coronary morbidity in Spain and on the effect of the principal risk factors on risk of coronary heart disease. The objective of this study is to describe the epidemiology of coronary disease (incidence, mortality and its association with cardiovascular risk factors) using the information gathered by primary care practitioners on cardiovascular health of their population.MethodsA prospective study was designed. Eight primary-care centres participated, each contributing to the constitution of the cohort with the entire population covered by the centre. A total of 6124 men and women aged over 25 years and free of cardiovascular disease agreed to participate and were thus enrolled and followed-up, with all fatal and non-fatal coronary disease episodes being registered during a 5-year period. Repeated measurements were collected on smoking, blood pressure, weight and height, serum total cholesterol, high-density and low-density lipoproteins and fasting glucose. Rates were calculated for acute myocardial infarction and ischaemic heart disease. Associations between cardiovascular risk factors and coronary disease-free survival were evaluated using Kaplan-Meier and Cox regression analyses.ResultsMean age at recruitment was 51.6 ± 15, with 24% of patients being over 65. At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers. During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate analyses. After multivariate adjustments, age, male gender, smoking, high total cholesterol, high HDL/LDL ratio, diabetes and overweight remained strongly associated with risk. Relative risks for hypertension in women and for diabetes in men did not reach statistical significance.ConclusionDespite high prevalence of vascular risk factors, incidence rates were lower than those reported for other countries and other periods, but similar to those reported in the few population-based studies in Spain. Effect measures of vascular risk factors were mainly as reported worldwide and support the hypothesis that protective factors not considered in this study must exist as to explain low rates. This study shows the feasibility of conducting epidemiological cohort studies in primary-care settings.

It has been demonstrated that the activity of the sodium-proton exchanger (NHE-1 isoform) is increased in lymphocytes and other blood cells from patients with essential hypertension. In the present study, we investigated whether an increased level of NHE-1-specific mRNA in lymphocytes from patients with essential hypertension would explain the enhanced transport activity. Twenty-two hypertensive patients and 21 normotensive subjects were studied. Basal cytosolic pH was measured by the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Maximal sodium-proton exchange activity was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The transcript level of NHE-1 was measured by reverse transcription-polymerase chain reaction in comparison with a constitutively expressed reference gene (beta-actin). Intracellular pH was lower in hypertensive patients than normotensive subjects (7.34 +/- 0.01 versus 7.39 +/- 0.01, mean +/- SEM, P < .001). The maximal activity of the sodium-proton exchanger was higher in hypertensive patients than in normotensive subjects (1262 +/- 100 versus 881 +/- 56 mmol/L cells per hour, P < .01). NHE-1 mRNA was increased in hypertensive patients compared with normotensive subjects (ratio of NHE-1 mRNA to beta-actin mRNA, 0.16 +/- 0.01 versus 0.12 +/- 0.02, P < .05). These data suggest that the increased sodium-proton exchange activity in essential hypertension may be related to the de novo synthesis of exchanger protein.

In this study, we investigated whether antihypertensive treatment with the angiotensin converting enzyme inhibitor quinapril modifies Na+/H+ exchanger activity or NHE-1 (isoform of the exchanger) mRNA expression in lymphocytes from patients with essential hypertension. Thirty-three hypertensive patients and 27 normotensive subjects were studied. Maximal sodium-proton exchange activity was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The transcript level of NHE-1 was measured by reverse transcription-polymerase chain reaction in comparison with a constitutively expressed reference gene (beta-actin). With the 100% confidence (upper) limit of the normotensive population as a cutoff point, a subgroup of 11 hypertensive patients had an abnormally high lymphocyte Na+/H+ exchange activity (group A). The activity of the exchanger was within the normal range in the remaining patients (group B). After 6 months of quinapril treatment the activity of the exchanger decreased to normal values (P < .001) in patients from group A, but remained unchanged in patients from group B. The NHE-1 mRNA expression was not modified with treatment neither in patients from the group A, nor in patients from the group B. These results suggest that chronic angiotensin enzyme inhibition with quinapril abolishes Na+/H+ exchange overactivity present in lymphocytes from a subgroup of hypertensive patients. This effect appears to be independent of changes in the expression of the mRNA encoding for the NHE-1 isoform of the exchanger.