Pulse pressure as a risk factor

There is abundant evidence that the increase in pulse pressure (PP) after the sixth decade of life is a surrogate risk marker for central artery stiffness. There is also evidence that central artery stiffness is an independent risk factor for cardiovascular disease. Still unsettled, however, is whether PP, the difference between systolic (SBP) and diastolic blood pressure (DBP), is superior to SBP or mean arterial pressure (MAP) as a predictor of cardiovascular risk. This controversy has been highlighted with the recent publication of the Prospective Studies Collaboration (PSC), which concluded that MAP at any age was a far superior predictor of risk than PP. Several lines of evidence that call into question the conclusions of the PSC, including the role of pulse wave reflection, are reviewed. Pulse pressure may be useful in predicting risk in the presence of both normal and compromised cardiac function. In addition, PP may be useful in predicting benefit of antihypertensive drug therapy. Finally, the advantages and disadvantages of using PP as a predictor of cardiovascular risk are reviewed and it is concluded that public health recommendations should remain focused on SBP as the overall prime target for defining risk and goal therapy.     

Hypertension as a cardiovascular risk factor in end-stage renal failure

There is a paucity of high quality studies on the prognostic importance of arterial pressure in end-stage renal disease. Furthermore, the optimal timing for blood pressure (BP) measurements (pre- or postdialysis), and the prognostic value of 24-hour ambulatory BP monitoring in these patients remain to be established. In end-stage renal disease patients without diabetes and heart failure, predialysis systolic, diastolic, and pulse pressure are strongly and independently related to left ventricular mass, and the strength of these relationships is higher than that between the corresponding postdialysis values and left ventricular mass. Average predialysis systolic pressure (monthly average) is associated with left ventricular mass as strongly as 24-hour systolic BP, which suggests that the average routine predialysis BP taken over 1 month may be equally representative of the “true” BP (the integrated BP load) than 24-hour ambulatory BP monitoring. Mortality is U shaped in large hemodialysis databases. In the only prospective study that adequately controlled for cardiac function at baseline, it was shown that hypertension is associated with a higher risk of developing congestive heart failure, and that patients with left ventricular hypertrophy or chronic heart failure are at a much higher risk of mortality than patients without these complications. The role of arterial stiffening (pulse pressure) as a cardiovascular risk factor has been firmly established in an analysis of a very large dialysis database in the United States, and by recent studies based on direct measurements of pulse wave velocity.     

Pulse pressure and risk of cardiovascular events in the systolic hypertension in the elderly program.

Pulse pressure has been related to higher risk of cardiovascular events in older persons. Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure. Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure. Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension, and the influence of treatment on the pulse pressure effect. We assessed the relation between pulse pressure, measured throughout the follow-up period, and the incidence of coronary heart disease (CHD), heart failure (HF), and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program, a 5-year randomized, placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults. In the treatment group, a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32% increase in risk of HF and a 24% increase in risk of stroke after controlling for systolic blood pressure and other known risk factors, as well as with a 23% increase in risk of HF and a 19% increase in risk of stroke after controlling for diastolic blood pressure and other risk factors. Pulse pressure was not significantly associated with HF or stroke in the placebo group, nor with incidence of CHD in either the placebo or treatment group. These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension.     

Elevated systolic blood pressure as a cardiovascular risk factor

This paper reviews the evolution of attitudes toward the treatment and diagnosis of hypertension. In particular, there is a growing realization that elevated systolic pressure may be a more valuable measurement in evaluating and controlling hypertension than is generally acknowledged. A large number of epidemiologic studies in a wide variety of populations have revealed that systolic blood pressure exerts a stronger influence than diastolic blood pressure. The largest of these, the Framingham Heart Study, showed that in subjects with systolic hypertension, diastolic blood pressure was only weakly related to the risk of cardiovascular events, but in those with diastolic hypertension, the risk of these events was strongly influenced by the level of systolic pressure. Furthermore, cardiovascular event rates were found to increase steeply with systolic pressure and were higher in cases of isolated systolic hypertension than diastolic hypertension. Clinical trials produced similar results, again suggesting that a greater reliance should be placed on systolic pressure in evaluating the risk of cardiovascular problems. This review concludes that the health community needs to be reeducated to consider the importance of systolic and diastolic blood pressure in assessing appropriate management strategies for hypertensive patients.     

Mild renal insufficiency as a cardiovascular risk factor in non-proteinuric type II diabetes

OBJECTIVES: To evaluate cardiovascular risk according to baseline renal function in a group of non-proteinuric type II diabetic patients. MATERIAL AND METHODS: Prospective study with a follow-up of 423 non-proteinuric type II diabetic patients with creatinine <150 micromol/l for an average of 4.7 years (S.D. 1.55). Creatinine clearance (CC) was estimated using the Cockcroft-Gault formula and expressed in millilitre per minute. The hazard ratio (HR) associated with each millilitre per minute decrease in baseline CC on fatal or non-fatal cardiovascular events and total mortality was evaluated using the Cox regression model. RESULTS: Baseline creatinine was 89 micromol/l (S.D. 15.9) and CC was 69.5 ml/min (S.D. 20). There were 63 cardiovascular events (15 unstable angina, 10 non-fatal myocardial infarctions, 25 non-fatal strokes, two amputations, nine fatal myocardial infarctions and two fatal strokes) and 39 total deaths (11 for cardiovascular causes). The cardiovascular event rate was 31.7/1000 patient-years and the total mortality rate was 19.6/1000 patient-years. The independent predictors of cardiovascular events were: CC (HR=1.035; confidence interval (CI) 95% 1.02-1.05; P<0.0001), total cholesterol/HDL cholesterol ratio (HR=1.25; CI 95% 1.1-1.4; P=0.0008), baseline coronary heart disease (HR=2.05; CI 95% 1.07-3.9; P=0.04) and baseline microalbuminuria (HR=2.3; CI 95% 1.3-3.8; P=0.003). The independent total mortality predictors were: CC (HR=1.04; CI 95% 1.02-1.08; P<0.0001), male (HR=2.1; CI 95% 1.1-4; P=0.027) and baseline microalbuminuria (HR=2.1; CI 95% 1.1-4;P=0.03). CONCLUSIONS: Mild renal insufficiency increases cardiovascular risk in non-proteinuric patients with type II diabetes.     

Oxidized high-density lipoprotein as a risk factor for cardiovascular events in prevalent hemodialysis patients

Background and objectivesHere, we assessed the impact of oxidized high-density lipoprotein (oxHDL), dysfunctional HDL, on mortality and cardiovascular disease (CVD) events in prevalent HD patients and compared oxHDL to interleukin-6 (IL-6), a strong predictor of CVD events in HD patients.Design, setting, participants, and measurementsThis prospective study examined a cohort of prevalent HD patients (n = 412). Blood samples were obtained at baseline to measure lipids, high-sensitive C-reactive protein (hsCRP), IL-6, oxidized low-density lipoprotein, N-terminal pro B-type natriuretic peptide, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase, adiponectin, and oxHDL. Carotid intima-media thickness (CIMT) was assessed at baseline and 3-year follow-up. Nutritional status was assessed by subjective global assessment (SGA), body mass index, and geriatric nutritional risk index (GNRI). After the baseline assessment, study patients were prospectively followed up (mean observational period, 40 months).ResultsAt baseline, patients with high oxHDL had a worse nutritional state and higher HDL-cholesterol (HDL-chol), ICAM-1, and adiponectin levels and a higher oxHDL/HDL-chol ratio than low oxHDL patients. A combination of high oxHDL and high IL-6 was significantly associated with increased CIMT at baseline and a larger increase in CIMT at 3-year follow-up. High oxHDL did not predict all-cause mortality; however, it was significantly associated with CVD-related mortality and composite CVD events, particularly with concomitant high IL-6. These associations were confirmed in multivariate Cox hazard models adjusted with confounding variables.ConclusionsHigh oxHDL, particularly with concomitant high IL-6, may be associated with an increased risk of CVD events and CVD-related mortality in prevalent HD patients.     

Aldosterone as a cardiovascular risk factor.

Aldosterone exerts cardiovascular effects by influencing epithelial fluid and electrolyte excretion, and thus blood volume and pressure. Mineralocorticoid receptors (MR) are found in epithelial and non-epithelial tissues (vessel walls, heart, brain), with high affinity for aldosterone and physiological glucocorticoids cortisol and corticosterone. MR blockade by spironolactone or eplerenone favorably affects cardiovascular outcomes. In some situations (primary aldosteronism, experimental mineralocorticoid administration) activation of cardiovascular MR reflects aldosterone levels inappropriate for salt status. In others (heart failure, essential hypertension) aldosterone and Na(+) status are often normal pretreatment; cardiovascular MR may thus be activated by normal glucocorticoid levels after tissue damage and reactive oxygen species generation. Therefore, although unilateral adrenalectomy is preferred therapy for unilateral aldosterone-producing adenoma or hyperplasia, MR blockade may be useful in cardiovascular diseases where aldosterone levels are normal.     

Gamma-glutamyltransferase as a cardiovascular risk factor.

The association of a novel factor with clinical vascular diseasemust meet the same high standard met by ‘traditional’risk factors. Serum gamma-glutamyltransferase (GGT) activityis a low-cost, highly sensitive laboratory test: though it iscurrently considered as an index of hepato-biliary dysfunctionand alcohol abuse,¹ pathology studies from our group since 1998have indicated its possible role in the pathogenesis of atherosclerosis.^2,3Furthermore, epidemiology studies on a total of 218 561subjects from unselected populations^4–6 or cohorts withascertained disease⁷ have proven the role of GGT not only inpredicting mortality from all causes, but also the clinical     

Obstructive sleep apnea as a risk factor for coronary events or cardiovascular death

Purpose  

This study aims to determine whether obstructive sleep apnea independently increases the risk of coronary events, including death from cardiovascular causes.     

Pulse pressure as a risk factor for peripheral vascular disease in type 2 diabetic patients

This study examined whether pulse pressure (PP) could be an independent predictor and associated with severity of peripheral vascular disease (PVD) in 396 type 2 diabetic patients (143 men and 253 women, aged 64.1 +/- 11.2 years). Peripheral vascular disease was diagnosed by an ankle-brachial index (ABI) < 0.90 and as severe PVD if ABI < 0.80. Association was evaluated before and after adjustment for age, sex, diabetes duration, hypertension, smoking, fasting plasma glucose (FPG), total cholesterol (TC), usage of insulin, and usage of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB); and for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), respectively. Results showed that PP increased from no (n = 348) to mild (n = 25) and severe (n = 23) PVD (one-way ANOVA, p < 0.001; multiple comparisons, p < 0.05 for any two groups). The PP increase from no to mild PVD was due to SBP increase; while further increase to severe PVD was due to both DBP drop and an even higher SBP. Adjusted odds ratio (AOR) for PVD for every 1-mmHg PP increment was 1.035 (1.012-1.058). When PP was categorized as tertiles (< 50, 50-59 and > or = 60 mmHg), respective AOR for PVD for second and third vs. first tertile was 2.605 (1.008-6.729) and 2.835 (1.123-7.156). Pulse pressure was also predictive for ABI independent of the effects of the confounders and the other parameters of blood pressure. In conclusion, PP was an independent predictor and correlated with severity of PVD in type 2 diabetic patients.     

Homocysteine as a risk factor for cardiovascular disease

Homocysteine is an amino acid that appears to damage the vascular endothelium and promote thrombosis. The most frequent causes of hyperhomocyst(e)inemia are the inherited defect of the enzyme cystathinonine B-synthase and nutritional deficiency of vitamin B(12) or folate. Hyperhomocyst(e)inemia is associated, perhaps causally, with atherosclerotic vascular disease. Interactions with risk factors such as cigarette smoking, hyperlipidemia, and hypertension are possible, but not yet defined. Dietary supplementation with vitamin B(12), folate, and other substances can reduce homocysteine levels. Such simple measures may reduce the risk of vascular disease in hyperhomocyst(e)inemic subjects.     

Hypothyroidism as a risk factor for cardiovascular disease

The cardiovascular risk in patients with hypothyroidism is related to an increased risk of functional cardiovascular abnormalities and to an increased risk of atherosclerosis. The pattern of cardiovascular abnormalities is similar in subclinical and overt hypothyroidism, suggesting that a lesser degree of thyroid hormone deficiency may also affect the cardiovascular system. Hypothyroid patients, even those with subclinical hypothyroidism, have impaired endothelial function, normal/depressed systolic function, left ventricular diastolic dysfunction at rest, and systolic and diastolic dysfunction on effort, which may result in poor physical exercise capacity. There is also a tendency to increase diastolic blood pressure as a result of increased systemic vascular resistance. All these abnormalities regress with L-T₄ replacement therapy. An increased risk for atherosclerosis is supported by autopsy and epidemiological studies in patients with thyroid hormone deficiency. The “traditional” risk factors are hypertension in conjunction with an atherogenic lipid profile; the latter is more often observed in patients with TSH>10 mU/L. More recently, C-reactive protein, homocysteine, increased arterial stiffness, endothelial dysfunction, and altered coagulation parameters have been recognized as risk factors for atherosclerosis in patients with thyroid hormone deficiency. This constellation of reversible cardiovascular abnormalities in patient with TSH levels<10 mU/L indicate that the benefits of treatment of mild thyroid failure with appropriate doses of l-thyroxine outweigh the risk.     

Homocysteine as a cardiovascular risk factor

Hyperhomocysteinemia (HH), a known risk factor for vascular diseases, is a frequent condition in hemodialysis (HD) patients. HH induces an oxidant stress to the vascular endothelium, causing a failure of vasodilation and an impairment of the antithrombotic properties. Vitamins B(6), B(12) and folic acid are important cofactors for the enzymes in the catabolism of homocysteine (Hcy). Failure of Hcy catabolism forces the cell to export Hcy into the plasma. The kidney is an important metabolic site for removal (up to 70%) of plasma Hcy (P-Hcy). HD lowers the P-Hcy concentration by 29 and 41% with cellulosic and noncellulosic membranes, respectively, yet values return to normal in only a few patients. Clearly, we must decrease the dangerous high levels of Hcy in different ways. Vitamin Supplementation: Vitamins B(6), B(12) and folic acid decreased the basal level of Hcy by about 40%, starting from the sixth month. Membranes: Some membranes performed better than the others. Techniques: On the chronic basis, in our 1-year experience, paired filtration dialyis led to the best results, when compared to bicarbonate dialysis and acetate-free biofiltration. Finally, as in HD patients no one type of treatment can normalize the P-Hcy concentration, we should try other, different strategies such as absorption, the use of liposomes and new types of supplementation.     

Mild gestational diabetes as a risk factor for congenital cryptorchidism

CONTEXT: Cryptorchidism is the most common malformation in newborn boys. Maternal diabetes has previously been suggested to be a risk factor for this disorder in one epidemiological study. OBJECTIVE: Evaluation of the prevalence of maternal glucose metabolism disorders during pregnancy in newborn boys having normal testicular descent or congenital cryptorchidism. DESIGN: Postnatal analysis of maternal history concerning glucose metabolism abnormalities during pregnancy among cryptorchid and healthy Finnish boys. SETTING AND PARTICIPANTS: The material of this case-control study comprises 1163 boys with normal testicular descent at birth and 125 boys with congenital cryptorchidism. All these singleton Finnish boys were born in Turku University Central Hospital (1997-2001) and were examined at birth and/or at the expected date of delivery. MAIN OUTCOME MEASURES: Information about maternal diabetes diagnosis and abnormality of the result of a 2-h 75-g oral glucose tolerance test during pregnancy were obtained from the hospital records after delivery. RESULTS: After adjustment for possible confounding factors, i.e. maternal smoking during pregnancy, maternal age at delivery, and risk factors of cryptorchidism, e.g. prematurity and weight for gestational age, abnormal maternal glucose metabolism was significantly more common in the group of cryptorchid boys [diet-treated gestational diabetes, P = 0.0001; odds ratio, 3.98 (95% confidence interval, 1.97-8.05); diet-treated gestational diabetes or only an abnormal result in oral glucose tolerance test, P = 0.0016; odds ratio, 2.44 (95% confidence interval, 1.40-4.25)] when compared with boys with normal testicular descent. CONCLUSIONS: Mildly abnormal glucose metabolism during pregnancy was associated with an increased risk for congenital cryptorchidism. The mechanism remains to be elucidated.     

Pulse pressure amplification and risk of cardiovascular disease

BACKGROUND: Whether pulse pressure amplification (PPA) relates to established markers of cardiovascular risk is unknown. The purpose of this study was to investigate the relationship between PPA and cardiovascular risk factors and cardiovascular risk in a population-based sample of 40- to 80-year old men. METHODS: A cross-sectional, single-center study was performed in 400 men aged 40-80 years. PPA was calculated as a ratio (brachial pulse pressure/central pulse pressure). Detailed information on vascular risk factors was obtained. Aortic pulse wave velocity (PWV) and common carotid intima-media thickness (CIMT), as markers of vascular risk, were measured. We calculated the absolute 10-year risk of coronary heart disease using the Framingham risk score. Regression analysis was used to evaluate the relations under study. RESULTS: In models adjusted for age, mean arterial pressure (MAP), heart rate, and height, significant inverse relations with PPA were found for waist-to-hip ratio, triglycerides, smoking, pack-years, and hypertension. Furthermore, an increased PPA was significantly inversely related to aortic PWV, common CIMT, and history of symptomatic vascular disease. Finally, the Framingham risk score decreased with increasing PPA. CONCLUSION: Our study shows that a higher PPA reflects a lower vascular risk in men between 40 and 80 years of age, as shown by a better cardiovascular risk profile, a reduced PWV, common CIMT, and a lower Framingham risk of coronary heart disease.