The influence of hemodynamic factors on left ventricular mass.

We evaluated the relationship between the variability in the left ventricular mass index (LVMI) and different hemodynamic factors. LVMI was associated with blood pressure and, in one subgroup, strongly to arterial pulse wave velocity (PWV). High physical activity was connected to increased LVMI, and a combination of low stroke index (SI) and high heart rate (HR) to decreased LVMI.

Pulse wave velocity reference values in healthy adults aged 26-75 years.

The stiffening of arteries is associated with various cardiovascular diseases. Arterial stiffening can be studied utilizing arterial pulse wave velocity (PWV), but the absence of reliable reference values for PWV has limited its use in clinical practice. The aim of this study was to establish a range of reference values for PWV. PWV was examined by measuring the time difference of systolic pulse waves in arteries from the aortic arch to the popliteal artery using whole-body impedance cardiography (ICG). The study population consisted of 799 individuals (age range 25-76 years), 283 of whom had no evidence of cardiovascular disease, and a low burden of risk factors was selected to represent an apparently healthy population. In healthy study population, PWV was higher in males (8 x 9 +/- 1 x 8 m s(-1)) than females (8 x 1 +/- 2 x 0 m s(-1), P<0 x 001). Young males had lower PWV values than old males. Correspondingly, young females also had lower PWV values than old females. PWV was clearly associated with age, and PWV was higher in young and middle-aged males than in females. There was no statistically significant difference between old males and females in PWV. In conclusion, whole-body ICG provides a practical method for PWV measurement. Reference values can be useful in the clinical management of patients, especially in detecting early vascular disease or an increased risk of cardiovascular complications.

Atrial fibrillation in elderly patients after coronary artery bypass grafting; gender differences in outcome.

OBJECTIVES: To evaluate gender-related differences in preoperative risk factors, hospital events, especially atrial fibrillation (AF), and length of stay in elderly patients undergoing isolated coronary artery bypass grafting (CABG). DESIGN: Prospectively collected data from consecutive patients undergoing isolated CABG in Tampere University Hospital between May 1999 and November 2000, in total 1131 patients. RESULT: We analysed 621 patients 65 years and older of whom 401 (65%) were male. When evaluating gender differences we found that the women were older (73 vs. 71 yrs, p<0.001) and significantly more often had hypertension (66% vs. 49%, p<0.001) and chronic heart insufficiency (11% vs. 4%, p=0.001). The NYHA classification of the women was worse (3.4 vs. 3.1, p<0.001) and in the angiographic data they had left main stenosis more often (31% vs. 21%, p=0.005) than the men. The women needed longer hospitalisation (19 vs. 15 days, p<0.001). There was no difference in the prevalence of postoperative AF between the genders, but in spite of that women had more postoperative strokes (6% vs. 3%, p=0.028) and also other major complications (29% vs. 19%, p=0.004) than the men. The 30-day mortality was higher in the female group (8% vs. 5%, p=0.06). We analysed preoperative risk factors and found that the females had a 1.6-fold risk for postoperative major complication after adjustment for age and other risk factors. In a logistic regression analysis age and the number of anastomoses emerged as independent predictors of AF in males, but in females we could not find any predictor for postoperative AF. CONCLUSIONS: The women are older and have more comorbidities and risk factors at the time of CABG. They also have more postoperative complications, but not a significantly higher mortality. Importantly, the excess of morbidity remains after adjustment for age and underlying risk factors. There is no gender difference in the incidence of postoperative AF in the elderly population. However, it seems to occur independent of age in the women only.

Demographics, treatment regimens and the use of angiotensin-receptor blockers in heart failure: findings from the Valsartan Heart Failure Trial.

Heart failure is the only major cardiovascular disease with an incidence and prevalence that continue to increase in the developed world. Early identification and correct treatment of the condition are of paramount importance. In recent years, there has been growing interest in identifying the differences between patients in terms of their risk of heart failure and response to treatment. Differences between men and women, different age groups, patients with varying aetiologies or comorbidities and differences between ethnic groups are only some of the factors that have been identified. This review surveys the available data on differences in responses to treatment, and discusses the use of angiotensin-receptor blockers in heart failure in light of the recent Valsartan Heart Failure Trial (Val-HeFT).

Heritability of left atrial size in the Tecumseh population.

BACKGROUND: Little is known about the determinants of atrial size, and no study has analyzed whether genetic factors are involved in the pathogenesis of LA enlargement. MATERIALS AND METHODS: We studied the heritability of echocardiographic left atrial size in 290 parents from the Tecumseh Blood Pressure Study and 251 children from the Tecumseh Offspring Study. All data from the parents and children were obtained at the same field office in Tecumseh, USA. Left atrial dimension was determined echocardiographically in accordance with American Society of Echocardiography guidelines with the use of leading-edge-to-leading-edge measurements of the maximal distance between the posterior aortic root wall and the posterior left atrial wall at end systole. RESULTS: For correlation between the left atrial dimensions of the parents and their offspring, several models were generated to adjust the atrial dimensions in both groups for an increasing number of clinical variables. After removing the effect of age, gender, height, weight, skinfold thickness, and systolic blood pressure, parent-child correlation for left atrial size was 0.19 (P = 0.007). Further adjustment for left ventricular mass and for measuring left ventricular diastolic function increased the correlation to 0.25 (P = 0.001). CONCLUSIONS: The present data indicate that heredity can explain a small but definite proportion of the variance in left atrial dimension.

Pulse pressure in tests improves the prediction of left ventricular mass: 10 years of follow-up.

Literature does not agree with the usefulness of exercise blood pressure (BP) in predicting hypertension or target organ damage. In this prospective 10 years of follow-up, we evaluated if exaggerated BP responses to tests may improve the prediction of left ventricular mass index (LVMI). At baseline, BP was recorded by casual measurements, and during tests using intra-arterial monitoring. The subjects were 97 healthy, untreated 35- to 45-year-old-men (34 normotensive, 29 borderline hypertensive, and 34 mild hypertensive). At 10-year follow-up, echocardiography was performed to 86 (89%) of them. Subjects not taking antihypertensive medication (n = 66) were included in the prediction of LVMI(g m-2). Echocardiography data at baseline was available from 70 (72%) of the subjects, of whom 52 did not use antihypertensive medication at follow-up. Pulse pressure (PP) at supine test (r = 0.337, P = 0.006), PP at dynamic exercise last work load (r = 0.332, P = 0.006), and PP after dynamic exercise (r = 0.316, P = 0.010) were the best BP variables achieved in tests in predicting future LVMI of the 66 subjects. Casual BP did not significantly correlate with future LVMI. The best model in predicting LVMI included PP achieved after dynamic exercise, family history of hypertension, and body mass index (BMI) (adj.R2 = 0.207). Baseline LVMI correlated significantly with future LVMI only among the 52 unmedicated subjects (r = 0.508, P<0.0001). The predictive value of baseline LVMI on future LVMI among them (adj.R2 = 0.243) was best improved by PP achieved in supine test and age (adj.R2 = 0.350). In conclusion, BP measurements during tests improved the prediction of LVMI compared with casual BP. For the first time, the pulsatile component of BP in tests was found to be the most significant BP parameter in predicting future LVMI.

Can blood pressure responses to tests unmask future blood pressure trends and the need for antihypertensive medication? Ten years of follow-up.

An exaggerated blood pressure (BP) response to test may unmask the subjects who have a high risk of developing hypertension. In this prospective 10 years of follow-up, we examined whether the predictive value of casual BP measurements on future BP level and need for antihypertensive medication could be improved by using BP responses to different physical tests. At baseline, BP was recorded by casual measurements and intra-arterial monitoring. During the intra-arterial BP recording, standardized postural and exercise tests were performed on 97 healthy, untreated men (34 normotensive, 29 borderline hypertensive, and 34 mild hypertensive). After 10 years of follow-up, 87 of them (90%) returned for casual and non-invasive 24-h BP measurements. At follow-up, 20 (23%) of the men had antihypertensive medication. The prediction of casual systolic blood pressure (SBP) was best improved by SBP at 10 min after the dynamic exercise test (adj. R2 = 0.448; adj. R2 = 0.356 for casual SBP alone). The prediction of casual diastolic blood pressure (DBP) was most improved by DBP at 10 min after the dynamic exercise test (adj. R2 = 0.282; adj. R = 0.259 for casual BP alone). SBP in the supine test best improved the prediction of 24-h SBP (adj. R2 = 0 448; adj. R2 = 0.275 for casual SBP alone). DBP in the standing test best improved the prediction of 24-h DBP (adj. R2 = 0.252; adj. R2 = 0.214 for casual DBP alone). Pre-exercise DBP and casual SBP were the best predictors of the need for antihypertensive medication (Cox-Snell R2 = 0.256; Cox-Snell R2 = 0.164 for casual SBP alone). In conclusion the prediction of future BP and need for antihypertensive medication can be improved by using BP measurements during postural and exercise tests. Future SBP is more predictable than DBP.

Antihypertensive treatment of patients with diabetes and hypertension.

Whereas individual research papers about antihypertensive treatment in diabetics might be somewhat confusing, the weight of the evidence strongly suggests that: 1) In patients with type 1 diabetes, it is advantageous to use angiotensin-converting enzyme (ACE) inhibitors as primary treatment. 2) In type 2 diabetics, aggressive blood pressure (BP) lowering is warranted and, the calcium antagonist controversy notwithstanding, all drugs appear to be similarly useful in reducing cardiovascular mortality. Specifically, in the Systolic Hypertension in Europe study, compared with placebo, a calcium antagonist dramatically reduced cardiovascular (CV) events in elderly diabetics. The Hypertension Optimal Treatment study showed that, using a calcium antagonist-based regimen, the degree of BP lowering determines the degree of CV event reduction. Furthermore, the United Kingdom Prospective Diabetes Study (UKPDS) did not find a difference in CV events reduction in patients treated with beta-blockers or with ACE inhibitors. In the UKPDS, the effect of BP lowering on reduction in CV events was more substantial than the degree of CV reduction by blood sugar lowering. 3) Both the CAPtopril Prevention Project (CAPPP) and the Heart Outcomes Prevention Evaluation (HOPE) studies found that treatment with an ACE inhibitor may be useful in reducing the incidence of new-onset type 2 diabetes mellitus. 4) Finally, insulin resistance, a precursor of diabetes mellitus and a strong predictor of future CV disease, is differentially affected by antihypertensive treatment. beta-Blockers and diuretics worsen insulin resistance, whereas alpha-adrenergic blockers and central imidazoline binding agents increase insulin sensitivity. The effect of ACE inhibitors and angiotensin blockers may also positively affect insulin resistance, but the results are not uniformly positive. It stands to reason that the differential effect of various drugs on insulin resistance and primary CV events may be clinically relevant particularly in the course of the long-term prevention of mild hypertension. All current trials investigate the effect of the treatment on secondary prevention of CV events among patients with advanced complicated diabetes and hypertension.

Pulse pressure is the best predictor of future left ventricular mass and change in left ventricular mass: 10 years of follow-up.

BACKGROUND: Ambulatory blood pressure correlates more closely with left ventricular mass (LVM) than casual blood pressure in cross-sectional studies, but prospective evidence is very limited. OBJECTIVE: To evaluate the best predictors of LVM and change in LVM during 10 years of follow-up, in a prospective study. METHODS: At baseline, blood pressure was recorded by casual measurements and 24 h intra-arterial ambulatory monitoring. The study participants were 97 healthy, untreated, 35-45-year-old men (34 normotensive, 29 borderline hypertensive, and 34 mildly hypertensive). At 10-year follow-up, echocardiography was performed in 86 (89%) of the men; echocardiographic data were available both at baseline and at follow-up from 70 (72%) of them. Individuals who were not receiving antihypertensive medication (n = 66) were included in the prediction of LVM index (LVMI), which was analysed as a continuous variable. RESULTS: The blood pressure variables that were best in predicting the LVMI were: 24 h pulse pressure (r = 0.308, P = 0.012), night-time pulse pressure (r = 0.291, P = 0.018), daytime pulse pressure (r = 0.253, P = 0.041), and casual systolic blood pressure (r = 0.212, P = 0.088). The LVMI was best predicted by a model including 24 h pulse pressure, positive family history of hypertension, body mass index, and age (adjusted coefficients of determination (adj.R2) = 0.197; that for the casual blood pressure model was adj.R2 = 0.140). During the follow-up, LVMI increased by +7.5 g/m2 and +23 g/m2 in individuals receiving and not receiving antihypertensive medication, respectively (P = 0.015). The change in LVMI was best predicted by the change in casual pulse pressure and use of antihypertensive medication (adj.R2 = 0.102). CONCLUSIONS: Ambulatory blood pressure improved the prediction of future LVMI compared with that obtained from casual measurements. To our knowledge, this is the longest prospective follow-up to show that pulse pressure is the most significant blood pressure parameter in predicting future LVMI and change in LVMI.

Prediction of blood pressure level and need for antihypertensive medication: 10 years of follow-up.

OBJECTIVE: To evaluate the usefulness of blood pressure and its variability in the prediction of future blood pressure and need for antihypertensive medication. METHODS: We used WHO criteria to classify, at baseline, 97 healthy untreated male volunteers as normotensive (n = 34), borderline hypertensive (n = 29) or mild hypertensive (n = 34), with casual measurements before intra-arterial 24 h ambulatory blood pressure monitoring. After 10 years of follow-up, 87 of the men (90%) were available and their blood pressure was recorded using casual measurements and non-invasive ambulatory 24 h monitoring. RESULTS: During the follow-up, the blood pressure classification deteriorated in 35 individuals (40%) and improved in six (7%) (McNemar test, P< 0.0001). In the borderline hypertensive group, 77% became hypertensive (P= 0.03). The 24 h mean systolic blood pressure was the best predictor of follow-up casual systolic (adj.R2 = 0.420) and 24 h systolic (adj.R2 = 0.540) blood pressure. The 24 h mean diastolic blood pressure was the best predictor of follow-up casual diastolic (adj.R2 = 0.301) and 24 h diastolic (adj.R2 = 0.292) blood pressure. The baseline casual systolic blood pressure also predicted the follow-up casual systolic blood pressure relatively well (adj.R2 = 0.356), but was clearly weaker for the follow-up 24 h systolic (adj.R2 = 0.275) blood pressure. The prediction of follow-up casual diastolic (adj.R2 = 0.259) and follow-up 24 h diastolic (adj.R2 = 0.214) blood pressure by baseline casual blood pressure was even weaker. The means and variabilities of the 24 h, daytime, and night-time blood pressures were the best predictors of the need for antihypertensive medication (Cox-Snell R2 = 0.399). The characteristics of the individual did not significantly predict future blood pressure and the need for antihypertensive medication. CONCLUSIONS: The 24 h mean blood pressure was an excellent predictor of the future blood pressure and the need for antihypertensive medication. Prediction of antihypertensive medication was further improved by also using blood pressure variability. Systolic blood pressure was more predictable than diastolic blood pressure.

Genetic contribution to the variance in left ventricular mass: the Tecumseh Offspring Study.

OBJECTIVE: To estimate the contribution of heredity to the variance in left ventricular mass (LVM), and to ascertain whether genetic factors may interact with non-genetic factors in promoting LVM growth. SUBJECTS AND SETTING: The study population consisted of 290 healthy parents and 251 healthy children living in Tecumseh, Michigan, USA. MAIN OUTCOME MEASURE: Correlation of parents' LVM with offspring's LVM adjusting for a number of clinical variables. METHODS: LVM in parents and offspring was measured with M-mode echocardiography by the same investigators. RESULTS: Parents unadjusted LVM was unrelated to offspring unadjusted LVM, but after removing the confounding effect of age, sex, anthropometric measurements, systolic blood pressure, plasma insulin and urinary sodium excretion, parent-child correlation for LVM was 0.28 (P = 0.006). The relative contribution of parental-adjusted LVM and of several offspring phenotypic and environmental variables on offspring LVM was evaluated by multivariable regression analysis. When age, gender, anthropometric measurements and systolic blood pressure were accounted for, adjusted LVM of parents explained only 1.6% of the total variance in offspring LVM. However, after inclusion of insulin and urinary sodium in the model heredity explained 7.6% of the total variance in offspring LVM, and its predictive power was second only to that of child's height. Furthermore, an interactive effect of parental LVM with offspring systolic blood pressure was found on child's left ventricular mass. CONCLUSION: Heredity can explain a small, but definite proportion of the variance in LVM. Higher blood pressure favors the phenotypic expression of the genes that regulate LVM growth.

Radial artery graft inflow from the undetached, unharvested RIMA: a method to avoid proximal anastomosis to the aorta in CABG surgery.

Performing the proximal anastomosis of a free arterial graft to the ascending aorta is problematic, especially if the wall of the aorta is calcified or thickened. We describe a method, which makes it possible to avoid this procedure.

The changing face of sympathetic overactivity in hypertension.

There is a lot of evidence showing that sympathetic activity is increased in a large proportion of patients with hypertension. However, the clinical impact of this state is frequently underestimated. Several factors seem to be misunderstood, such as whether sympathetic overactivity is reproducibly present, whether it lasts throughout 24 h, and what is the significance of its association with tachycardia. In this review, we present data to indicate that several haemodynamic changes in hypertension such as elevated cardiac output and heart rate and alteration in vascular resistance are neurogenic. The relationship between the increased sympathetic tone and decreased parasympathetic tone in hypertension is reciprocal, which strongly suggests that the abnormality emanates from the brain. The increase in sympathetic drive in hypertension is widespread across many organs. Beside the heart it is seen in the kidney and skeletal muscle, and even in platelets. We also discuss the possible mechanisms of the haemodynamic transition from this hyperkinetic state to established hypertension. We propose a hypothesis where down-regulation of beta-adrenergic responsiveness plays a major role in explaining the haemodynamic changes as well as metabolic alterations, such as hyperinsulinaemia and even the gain of weight in hypertension. Thus, the increased sympathetic tone may be involved in the genesis of multiple, pressure-independent coronary risk factors in hypertension.

Determinants of left ventricular structure and mass in young subjects with sympathetic over-activity. The Tecumseh Offspring Study.

OBJECTIVE: In this study, we tested the hypothesis that sympathetic over-activity may cause metabolic abnormalities and affect left ventricular (LV) structure and mass early in life. SUBJECTS AND SETTING: The study population consisted of 111 healthy adolescents and young adults living in Tecumseh, Michigan (USA). MAIN OUTCOME MEASURES: Correlations of LV mass and structure with several clinical variables in relation to the activity of the sympathetic nervous system. METHODS: Power spectrum density estimates of heart rate variability were calculated with an auto-regressive method, and subjects were divided by cluster analysis into two groups according to low-frequency and high-frequency components. LV data were obtained by echocardiographic assessment RESULTS: Subjects with signs of sympathetic over-activity (n = 38, group 1) had higher heart rate, blood pressure (BP), waist/hip ratio and cholesterol levels than the rest of the group (n = 73, group 2). In group 1 subjects, insulin emerged as the strongest univariate correlate of interventricular septum and posterior wall thicknesses (P< 0.001 for both) and of LV mass (P= 0.009). These relationships remained significant when body mass index was accounted for. By contrast, the marginal univariate relationship with diastolic BP did not remain significant in multivariate analysis. In group 2 subjects, BP was strongly correlated with LV wall thickness and mass both in univariate (P values from 0.03 to < 0.001) and multivariate analyses, while insulin was not. The interactive effect of sympathetic activity and insulin on echocardiographic data was confirmed by multivariate analyses performed in the subjects grouped together (P values from 0.02 to 0.001 for the sympathetic activity x insulin interaction term). CONCLUSIONS: In young subjects with heightened sympathetic activity and initial metabolic abnormalities, insulin is a strong determinant of LV wall thickness and geometry, while in subjects with normal autonomic nervous system activity, the main determinant of left ventricular size is the haemodynamic load.

Wide-band spectral analysis of blood pressure and RR interval variability in borderline and mild hypertension.

The aim of this study was firstly to investigate whether indices of wide-band spectral analysis in borderline hypertensive (BHT) or mildly hypertensive (HT) subjects differ from those in normotensive (NT) subjects, and secondly to assess the predictive value of these indices for future hypertension. Electrocardiogram and intra-arterial 24 h ambulatory blood pressure (BP) were recorded in 32 NT, 29 BHT and 30 HT middle-aged men. From the recordings, a 16 h period was extracted for wide-band spectral analysis. A single spectrum of BP and RR interval (RRI) variability was computed for each period by the fast Fourier transform method. The slopes of the spectra were assessed on a log-log scale by linear fitting of the spectral values. Power spectral densities were calculated over regions of 0-0.003, 0.003-0.04, 0.04-0.15, 0.15-0.40 and 0-0.4 Hz. No between-group differences were found in the slopes of BP and RRI spectra. The between-group differences in spectral powers for BP variability were almost invariably significant. The spectral powers for RRI variability did not show between-group differences. Five years later, 22 NT, 22 BHT and 18 HT subjects were re-assessed using casual BP measurements. In a logistic regression model for the combined group of NT and BHT subjects who became HT (22 of 44) during the five-year period, none of the parameters of wide-band spectrum predicted the development of hypertension. In conclusion, parameters of wide-band spectral analysis may not be useful in predicting future hypertension in NT and BHT subjects. Because the BP level is a major factor influencing BP variability, the between-group differences in wide-band spectral powers in BP may be due to differences in BP level rather than differences in cardiovascular regulatory mechanisms.

Circadian profile of low-frequency oscillations in blood pressure and heart rate in hypertension.

Electrocardiogram and intraarterial blood pressure (BP) were recorded in 35 normotensive (NT), 29 borderline hypertensive (BHT), and 30 mildly hypertensive (HT) men (aged 35 to 45 years) by the Oxford method over a 24-h period. Consecutive data segments of 5 min were extracted from the recordings for frequency domain analysis. Heart rate (HR) and BP variability was calculated for oscillations between 0.05 and 0.12 Hz, usually referred to as Mayer waves. Power and median frequency of the oscillations were determined. Some 10% of the segments were excluded from the analysis because of artifacts and transients. The results were averaged for 5-h periods in the evening, at night, and during the day. In the BHT subjects, the median frequency of the Mayer waves was shifted to lower frequencies as compared with the NT subjects. This was seen at night and during the day. The phenomenon presumably reflects an increased latency in the sympathetic vasomotor control of the baroreceptor reflex. No between-group differences were found in the normalized spectral power values. Five years later, 24 NT, 22 BHT, and 19 HT subjects were reassessed using casual BP and noninvasive ambulatory 24-h monitoring. In the initial phase, the median frequencies for the 5-h periods showed no evident linear relationship with the corresponding BP levels. However, the median frequencies showed high inverse correlations with the follow-up ambulatory BP levels. In the evening and during the day, the median frequency showed a significant inverse correlation also with the increment in BP. No clear relationship was found between power estimates and BP levels or future increments in BP. In conclusion, the frequency shift of Mayer waves to lower frequencies is associated with an increased risk of developing established hypertension.

Heart rate variability and progression of coronary atherosclerosis.

Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interval [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; mean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0. 04 to 0.02 mm) (P<0.001 between the tertiles). This association was abolished by gemfibrozil. SDNN was lower (P<0.001) and minimum HR was faster (P<0.01) in the patients with marked progression than in those with regression of focal coronary atherosclerosis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary atherosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001). Low HR variability analyzed from ambulatory ECG predicts rapid progression of coronary artery disease. HR variability provided information on progression of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.

Parental hyperdynamic circulation predicts insulin resistance in offspring: The Tecumseh Offspring Study.

Controversy surrounds the pathogenetic mechanisms of the relationship between hyperdynamic circulation and insulin resistance. Two hundred eight children and young adults (mean age, 17.2+/-3.0 years; range, 11 to 26 years) from the Tecumseh Offspring Study whose parents had been assessed with Doppler echocardiography at the age of 34 years during the previous Tecumseh Blood Pressure Study were considered for this analysis. Offspring data were stratified according to tertiles of parental cardiac index. Parents in the top cardiac index tertile had increased heart rate (P=0.001), stroke volume (P=0.0001), left ventricular fractional shortening (P=0.02), and plasma epinephrine (P=0.02) compared with parents in the other tertiles. Body mass index (BMI) and blood pressure were similar in all groups. Offspring of parents with a high cardiac index had greater BMI (P=0.001), skinfold thickness (P=0.008), and waist/hip ratio (P=0.02), higher diastolic blood pressure (P=0.02) and plasma insulin level (P=0.001), and higher heart rate during Stroop's color test (P=0.02) than offspring of parents with a lower cardiac index. In a multivariate regression analysis, offspring BMI was predicted by parental BMI and cardiac index (P=0.0001 and 0.003, respectively). The mother-child relationship explained most of the cardiac index-BMI association. In summary, parental hyperdynamic circulation was an important predictor of overweight, abnormal fat distribution, increased blood pressure, and hyperinsulinemia in offspring. Our results illustrate the complexity of interaction between a genetic tendency and its phenotypic expression. We speculate that the degree of beta-adrenergic responsiveness may be a major determinant of the phenotypic differences between the parents and offspring found in this study.

Associations between lipoproteins and the progression of coronary and vein-graft atherosclerosis in a controlled trial with gemfibrozil in men with low baseline levels of HDL cholesterol.

BACKGROUND: Lipid-lowering secondary-prevention trials of coronary artery disease (CAD) have implicated triglyceride-rich lipoproteins as the main determinants of angiographic progression after elevated LDL cholesterol levels have been lowered with therapy. The present study focuses on the lipoprotein determinants of angiographic CAD progression in men with low HDL cholesterol concentration as their main baseline lipid abnormality who underwent 32 months of randomized therapy with gemfibrozil or placebo. METHODS AND RESULTS: Men who had undergone coronary bypass surgery (n=372) completed a randomized, placebo-controlled study with gemfibrozil 1200 mg/d. They were selected primarily for HDL cholesterol levels that corresponded to the lowest third for middle-aged men. Average baseline lipid and lipoprotein levels were serum triglyceride, 1.60; serum cholesterol, 5.17; ultracentrifugally separated LDL cholesterol, 3.43; HDL2 cholesterol, 0.41; and HDL3 cholesterol, 0. 61 mmol/L. In the gemfibrozil group, these levels were reduced on average by 40%, 9%, and 6% or increased by 5% and 9%, respectively. On-trial IDL and LDL triglyceride and cholesterol levels significantly predicted global angiographic progression, taking into account changes in native segments and in bypass grafts. HDL3 but not HDL2 cholesterol concentration was associated with protection against progression, especially focal disease in native coronary lesions. VLDL was the lipoprotein most predictive of new lesions in vein grafts; IDL was also significantly related. CONCLUSIONS: This study expands the previous evidence of the triglyceride-rich lipoproteins, especially IDL, as predictors of angiographic progression of CAD but does not negate the significance of mildly elevated LDL levels. Of the HDL subfractions, only HDL3 was protective in this group of men selected for their low initial HDL levels.

Office and laboratory blood pressures as predictors of daily blood pressure level in normotensive subjects and borderline and mild hypertensive subjects.

A series of standardized laboratory tests [10 min sitting and supine, 9 min standing, dynamic; cycle ergometer (ERG) and isometric exercise; handgrip (HG)] were performed during intra-arterial blood pressure (BP) recording in 97 healthy unmedicated men, initially classified as normotensive (NT, n = 34), borderline hypertensive (BHT, n = 29) or mildly hypertensive (HT, n = 34) by repeated office blood pressure (OBP) measurements. After testing, a 24-h intra-arterial ambulatory BP (IABP) recording was obtained while subjects performed their normal activities. Day and night periods were analysed as well as 24-h averages for systolic BP (SBP) and diastolic BP (DBP) using Pearson correlations and multiple linear regressions. In normotensive subjects, the supine SBP predicted IABP measurements best (r range 0.39-0.69, P < 0.05-0.001). In multiple regression, supine SBP explained 49% of 24-h SBP variance (F = 12.4, P = 0.001). For BHT, supine SBP was also the best predictor (r range 0.09-0.64, P NS to P < 0.001), and it explained 37% of 24-h SBP variance (F = 15.6, P = 0.0005). In HT, ERG DBP correlated best with IABP (r range 0.52-0.75, P < 0.01-0.001). ERG SBP explained 49% of 24-h SBP (F = 31.0, P = 0.0000) and ERG DBP explained 56% of 24-h DBP (F = 35.4, P = 0.0000) variance. Laboratory BP correlations were generally better with day than with night measurements. OSBP correlated moderately well with IABP in NT, and weakly in BHT and HT; ODBP instead correlated with IABP in NT and HT but not significantly in BHT. In conclusion, OBP is less closely related to IABP than laboratory BP, but even laboratory BP generally explains less than 50% of IABP variance. Stressors such as exercise are useful only in HT. For BHT, the prediction of IABP with laboratory measures was even weaker than in other groups, and thus ambulatory measurements cannot be replaced by short-duration laboratory measurements and stress tests.