Alberto Mazza

Menopause does not affect blood pressure and risk profile, and menopausal women do not become similar to men.

Objective Menopause is considered to be a cardiovascular risk factor, but this belief is based on opinions rather than on evidence. Confounding effects of age are often neglected. Design Population-based study with further subanalysis of case-to-case age-matched cohorts of men and fertile and menopausal women. Setting Epidemiology in primary, public, institutional frame. Participants Nine thousand three hundred and sixty-four men and women aged 18–70 years representative of Italian general population followed-up for 18.8 ± 7.7 years. Main outcome measures Blood pressure (BP), prevalence and incidence of hypertension, serum total, high-density lipoprotein and low-density lipoprotein cholesterol, glucose tolerance, body adiposity, vascular reactivity, target organ damage, overall and cardiovascular mortality and morbidity, by gender and by menopausal status. Results Cross-sectional: crude BP, pressor response to cold, orthostatic BP decrease, BMI, skinfold thickness, fasting and postload blood glucose and insulin, serum lipids, left ventricular mass, serum creatinine, microalbuminuria and augmetantion index were higher in menopausal than in fertile women, and comparable in menopausal women and men, a difference that was no longer present when adjusting for age or considering age-matched cohorts. Longitudinal: BP increase during follow-up, cardiovascular mortality and morbidity were greater in menopausal than in fertile women, and comparable in menopausal women and men, a difference no longer present in age-matched cohorts. Menopausal status was rejected from multivariate Cox analysis also including age. Conclusion The cardiovascular effects usually attributed to menopause seem to be a mere consequence of the older age of menopausal women.

Predictors of stroke mortality in elderly people from the general population

Stroke occurs particularly frequently in elderly people and, being more often disabling than fatal, entails a high social burden. The predictors of stroke mortality have been identified in 3282 subjects aged ≥65 years, taking part in the CArdiovascular STudy in the ELderly (CASTEL), a population-based study performed in Northeast Italy. Historical and clinical data, blood tests and 14-year fatal events were recorded. Continuous items were divided into quintiles and, for each quintile, adjusted relative risk (RR) with 95% confidence intervals [CI] was derived from multivariate Cox analysis. Age, historical stroke (RR: 5.2; 95% CI: 3.18–8.6) and coronary artery disease (RR: 1.38; CI: 1.18–2.1), atrial fibrillation (RR: 2.40; CI: 1.42–4.0), arterial hypertension (RR: 1.33; CI: 1.15–1.76), systolic blood pressure ≥ 163 mmHg (RR: 1.84; CI: 1.20–2.59), pulse pressure ≥74 mmHg (RR: 1.50; CI: 1.13–2.40), cigarette smoking (RR: 1.60; CI: 1.03–2.47), electrocardiographic left ventricular hypertrophy (RR: 1.72; CI: 1.10–2.61), impaired glucose tolerance (IGT, RR: 1.83; CI: 1.10–3.0), uric acid (UA) >0.38 mmol/l (RR: 1.61; CI: 1.14–2.10), serum potassium ≥5 mEq/l (RR: 1.70; CI: 1.24–2.50) and serum sodium ≤139 mEql/l (RR: 1.34; 1.10–2.10) increased the risk of stroke. In the CASTEL, stroke was the first cardiovascular cause of death. Some independent predictors usually unrelated to stroke mortality (namely pulse pressure, pre-diabetic IGT, UA and blood electrolytes disorders) have been identified.

Determination of the Longest Intrapatient Left Ventricular Electrical Delay May Predict Acute Hemodynamic Improvement in Patients After Cardiac Resynchronization Therapy

Background—One of the reasons for patient nonresponse to cardiac resynchronization therapy is a suboptimal left ventricular (LV) pacing site. LV electric delay (Q-LV interval) has been indicated as a prognostic parameter of cardiac resynchronization therapy response. This study evaluates the LV delay for the optimization of the LV pacing site. Methods and Results—Thirty-two consecutive patients (23 men; mean age, 71±11 years; LV ejection fraction, 30±6%; 18 with ischemic cardiomyopathy; QRS, 181±25 ms; all mean±SD) underwent cardiac resynchronization therapy device implantation. All available tributary veins of the coronary sinus were tested, and the Q-LV interval was measured at each pacing site. The hemodynamic effects of pacing at different sites were evaluated by invasive measurement of LV dP/dtmax at baseline and during pacing. Overall, 2.9±0.8 different veins and 6.4±2.3 pacing sites were tested. In 31 of 32 (96.8%) patients, the highest LV dP/dtmax coincided with the maximum Q-LV interval. Q-LV interval correlated with the increase in LV dP/dtmax in all patients at each site (AR1 &rgr;=0.98; P<0.001). A Q-LV value >95 ms corresponded to a >10% in LV dP/dtmax. An inverse correlation between paced QRS duration and improvement in LV dP/dtmax was seen in 24 patients (75%). Conclusions—Pacing the LV at the latest activated site is highly predictive of the maximum increase in contractility, expressed as LV dP/dtmax. A positive correlation between Q-LV interval and hemodynamic improvement was found in all patients at every pacing site, a value of 95 ms corresponding to an increase in LV dP/dtmax of ≥10%.

Serum uric acid shows a J-shaped trend with coronary mortality in non-insulin-dependent diabetic elderly people. The CArdiovascular STudy in the ELderly (CASTEL).

The relationship between serum uric acid (SUA) and risk of coronary heart disease (CHD) mortality remains controversial, particularly in diabetic subjects. The aim of the present study is to evaluate whether SUA independently predicts CHD mortality in non-insulin-dependent elderly people from the general population and to investigate the interactions between SUA and other risk factors. Five hundred and eighty-one subjects aged ≥65 years with non-insulin-dependent diabetes mellitus were prospectively studied in the frame of the CArdiovascular STudy in the ELderly (CASTEL). Historical and clinical data, blood tests and 12-year fatal events were recorded. SUA as a continuous item was divided into tertiles and, for each tertile, adjusted relative risk (RR) with 95% confidence intervals (CI) was derived from multivariate Cox analysis. CHD mortality was predicted by SUA in a J-shaped manner. Mortality rate was 7.9% (RR 1.28, CI 1.05–1.72), 6.0% (reference tertile) and 12.1% (RR 1.76, CI 1.18–2.27) in the increasing tertiles of SUA, respectively, without any difference between genders. In diabetic elderly subjects, SUA independently predicts the risk of CHD mortality in a J-shaped manner.

Triglycerides + high‐density‐lipoprotein‐cholesterol dyslipidaemia, a coronary risk factor in elderly women: the CArdiovascular STudy in the ELderly

Abstract

Predictors of mortality in very old subjects aged 80 years or over

We studied 318 subjects aged 80 years or over included in the Cardiovascular Study in the Elderly (CASTEL). Some well known risk factors (left ventricular hypertrophy, glucose intolerance, cholesterol, ApoB/ApoA ratio,. triglycerides, proteinuria, cigarette smoking, and ECG abnormalities), whose importance m cardiovascular risk is definitely accepted for young adults, were very poor predictors of mortality in our survey. On the contrary, FEV1 reduction and blood uric acid were strong predictors.

C-344T polymorphism of the aldosterone synthase gene and blood pressure in the elderly: a population-based study.

Objectives Whether the C-344T polymorphism of the aldosterone synthase gene is important for blood pressure control remains controversial. It has been proposed that an association between this polymorphism and blood pressure might be evident in elderly subjects. The aim of the present study was to test this hypothesis in an epidemiological context. Design A cross-sectional epidemiological evaluation of a highly homogeneous unselected general population of elderly Caucasians. Methods Lifestyle, medical history, anthropometrics, skinfold thickness, supine blood pressure, heart rate and biochemical measures were recorded in 437 subjects aged ≥ 65 years living in a secluded valley. All were genotyped for C-344T allele status and underwent measurements of plasma aldosterone and renin. Results The C-344T genotypic frequency did not deviate from Hardy–Weinberg equilibrium. The aldosterone to renin ratio was 19% lower in the CC than in the TT genotype. Systolic blood pressure was significantly lower in subjects with the CC genotype, higher in the TT (+9.6 mmHg versus CC) and intermediate in the CT (+7.9 mmHg versus CC). Adjustment for age, gender, smoking and antihypertensive treatment did not affect this association. Diastolic blood pressure did not differ across genotypes. A significant increase of systolic blood pressure with increasing age and with increasing skinfold thickness was observed in the TT homozygotes but not in the C-carriers. Conclusions These data support the concept that the C-344T polymorphism plays a role in controlling systolic blood pressure and the age-related increase in systolic blood pressure in response to age and to body fat, possibly through differences in modulation of aldosterone synthesis.

Determination of the Longest Intra-Patient Left Ventricular Electrical Delay May Predict Acute Hemodynamic Improvement in Cardiac Resynchronization Therapy Patients

Background—One of the reasons for patient nonresponse to cardiac resynchronization therapy is a suboptimal left ventricular (LV) pacing site. LV electric delay (Q-LV interval) has been indicated as a prognostic parameter of cardiac resynchronization therapy response. This study evaluates the LV delay for the optimization of the LV pacing site. Methods and Results—Thirty-two consecutive patients (23 men; mean age, 71±11 years; LV ejection fraction, 30±6%; 18 with ischemic cardiomyopathy; QRS, 181±25 ms; all mean±SD) underwent cardiac resynchronization therapy device implantation. All available tributary veins of the coronary sinus were tested, and the Q-LV interval was measured at each pacing site. The hemodynamic effects of pacing at different sites were evaluated by invasive measurement of LV dP/dtmax at baseline and during pacing. Overall, 2.9±0.8 different veins and 6.4±2.3 pacing sites were tested. In 31 of 32 (96.8%) patients, the highest LV dP/dtmax coincided with the maximum Q-LV interval. Q-LV interval correlated with the increase in LV dP/dtmax in all patients at each site (AR1 &rgr;=0.98; P<0.001). A Q-LV value >95 ms corresponded to a >10% in LV dP/dtmax. An inverse correlation between paced QRS duration and improvement in LV dP/dtmax was seen in 24 patients (75%). Conclusions—Pacing the LV at the latest activated site is highly predictive of the maximum increase in contractility, expressed as LV dP/dtmax. A positive correlation between Q-LV interval and hemodynamic improvement was found in all patients at every pacing site, a value of 95 ms corresponding to an increase in LV dP/dtmax of ≥10%.

Weak effect of hypertension and other classic risk factors in the elderly who have already paid their toll

The aim of the CASTEL, a population-based (n = 3282) prospective study which began 14 years ago, was to identify those items which had a prognostic impact in the elderly, and to evaluate whether the typical cardiovascular risk factors, particularly arterial hypertension, play a role after the age of 65 years. Initial screening, final follow-up and annual detection of mortality were performed. Mantel–Hanszel approach and multivariate Cox model were used for statistics. Cardiovascular mortality was 23.3% in normotensive, 23.3% in borderline, and 25% in the sustained hypertensive subjects (insignificant difference). In women, the incidence of stroke and coronary artery disease weakly depended on pulse pressure. Historical stroke and myocardial infarction predicted cardiovascular mortality in women; diabetes, uricaemia and high heart rate in men. In the very old, the predictors were less numerous, and blood pressure was not a predictor whatsoever; pulse blood pressure and murmurs at the neck were especially predictive in women, historical heart failure, proteinuria and tachycardia in men, historical stroke and myocardial infarction, pulmonary disease, left ventricular hypertrophy, diabetes and uricaemia in both genders. The elderly have a different cardiovascular risk pattern compared to younger people. Hypertension is not a predictor of coronary and stroke mortality. Prognosis depends on pulse pressure rather than on the label ‘hypertension’. Hypercholesterolaemia is not a risk factor. This could simply indicate that elderly persons are the survivors in a population where significant mortality has already made its mark, eliminating those with the worst risk pattern. The two genders have a different risk profile due to sex-specific susceptibility to risk factors.

Total cholesterol and mortality in the elderly

Abstract Casiglia E, Mazza A, Tikhonoff V, Scarpa R, Schiavon L, Pessina AC (Department of Clinical and Experimental Medicine, University of Padova, Italy). Total cholesterol and mortality in the elderly. J Intern Med 2003; 254: 353–362.