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.     

Plasma sphingomyelin level as a risk factor for coronary artery disease

Only a fraction of the clinical complications of atherosclerosis are explained by known risk factors. Animal studies have shown that plasma sphingomyelin (SM) levels are closely related to the development of atherosclerosis. SM carried into the arterial wall on atherogenic lipoproteins may be locally hydrolyzed by sphingomyelinase, promoting lipoprotein aggregation and macrophage foam cell formation. A novel, high-throughput, enzymatic method to measure plasma SM levels has been developed. Plasma SM levels were related to the presence of coronary artery disease (CAD) in a biethnic angiographic case-control study (279 cases and 277 controls). Plasma SM levels were higher in CAD patients than in control subjects (60+/-29 versus 49+/-21 mg/dL, respectively; P:<0. 0001). Moreover, the ratio of SM to SM+phosphatidylcholine (PC) was also significantly higher in cases than in controls (0.33+/-0.13 versus 0.29+/-0.10, respectively; P:<0.0001). Similar relationships were observed in African Americans and whites. Plasma SM levels showed a significant correlation with remnant cholesterol levels (r=0.51, P:<0.0001). By use of multivariate logistic regression analysis, plasma SM levels and the SM/(SM+PC) ratio were found to have independent predictive value for CAD after adjusting for other risk factors, including remnants. The odds ratio (OR) for CAD was significantly higher for the third and fourth quartiles of plasma SM levels (OR 2.81 [95% CI 1.66 to 4.80] and OR 2.33 [95% CI 1.38 to 3. 92], respectively) as well as the SM/(SM+PC) ratio (OR 1.95 [95% CI 1.10 to 3.45] and OR 2.33 [95% CI 1.34 to 4.05], respectively). The findings indicate that human plasma SM levels are positively and independently related to CAD. Plasma SM levels could be a marker for atherogenic remnant lipoprotein accumulation and may predict lipoprotein susceptibility to arterial wall sphingomyelinase.     

Plasma homocysteine is not a major risk factor for vascular disease in growth hormone deficient adults

OBJECTIVE: Several cardiovascular risk factors have been investigated in patients with adult growth hormone deficiency (GHD) to explain the observed increase in vascular mortality. Plasma homocysteine concentration has been identified recently as an independent risk factor for atherosclerosis. We wished to determine whether plasma homocysteine contributes to cardiovascular risk in adult GHD. METHOD: Plasma homocysteine was measured by fluorescence polarization immunoassay in 45 GH-deficient adults on stable conventional hormone replacement (25M, 20F), age range 23-76 years, and compared with 55 matched controls (30M, 25F), age range 21-77 years. All subjects were free from clinical hypertension, diabetes, ischaemic heart disease and peripheral vascular disease. Blood pressure, body mass index and waist hip ratio were recorded. Serum creatinine and fasting lipids were measured. Serum vitamin B12 and folate levels, important cofactors in the homocysteine metabolic pathways, were also measured. RESULTS: Homocysteine levels were not different in patients and controls (9.75 [7.8-11.6] micromol/l vs. 9.65 [8.3-11.5] micromol/l, respectively, P = 0.88). Serum vitamin B12 was also not different (320.5 [262.0-427.5] pmol/l vs. 313.5 [277.0-460.5] pmol/l, respectively, P = 0.77). Serum folate levels were significantly lower in the patient group (7.05 [5.12-8.27] ng/ml vs. 7.80 [6.52-10.60] ng/ml, respectively, P = 0.03). When separated by gender, in males folate was not significantly different between patients and controls 7.05 [5.17-9.19] vs. 7.65 [6.15-10.22], P = 0.264, whereas in females, folate was significantly lower in patients at 7.05 [4.57-7.75] compared to controls at 8.4 [6.60-12.20], P = 0.01. CONCLUSION: Plasma homocysteine levels are not significantly elevated in GH-deficient adults and are unlikely to be a major risk factor for vascular disease in these individuals.     

Homocysteine: a novel risk factor in vascular disease

Homocysteine is a sulphydryl-containing aminoacid derived from the metabolic demethylation of methionine. Moderately raised concentrations of total homocysteine (tHcy) have been correlated with an increased risk of atherothrombotic vascular events. The prevalence of hyperhomocysteinaemia has been estimated to be about 5% in the general population, and 13–47% among patients with symptomatic atherosclerotic vascular disease. Nutritional deficiencies in the vitamin cofactors (folate, vitamin B12, and vitamin B6) required for homocysteine metabolism may promote hyperhomocysteinaemia. Clinical and experimental studies suggest that high homocysteine concentrations may cause the atherogenic and thrombotic tendencies of homocystinuric and hyperhomocysteinaemic patients. Experimental evidence suggests that the atherogenic propensity associated with hyperhomocysteinaemia results from endothelial dysfunction and injury followed by platelet activation and thrombus formation. The treatment of hyperhomocysteinaemia varies with the underlying cause; however, vitamin supplementation (with folic acid, pyridoxine [vitamin B₆], and vitamin B₁₂) is generally effective in reducing homocysteine concentrations. Before advocating widespread screening of patients with atherosclerotic vascular disease, we must have a clearer understanding of the clinical efficacy of potential therapeutic interventions. Prospective, randomized clinical trials, however, will be necessary to determine the effect of vitamin supplementation on cardiovascular morbidity and mortality.     

Diabetes mellitus as a risk factor in vascular surgery

The paper reports a series of 23 diabetic patients affected by occlusive arterial disease of the lower limbs treated by reconstructive vascular surgery. Revascularisation interventions were performed in 9 patients affected by claudication, with good long-term results. Fourteen patients underwent operations for limb salvage. The major amputation rate was 35%.     

Proteinuria is a risk factor for proximal type of peripheral vascular disease in type 2 diabetic patients

The levels of creatinine, urea, uric acid, UPE and blood pressure were measured in the groups of Type 2 diabetics with proximal (iliocofemoral) type (PRMA) and distal (tibial) type of macroangiopathy (DIMA) (diagnosed by means of Doppler ultrasound technique) and in a control group without lower limb macroangiopathy. Both UPE and creatinine mean values were significantly increased in the PRMA group in comparison with controls. Uric acid levels were increased in both PRMA and DIMA groups and mean urea values did not differ significantly in all three groups of patients. Systolic blood pressure values were similar in each group as well. However, a significant increase of mean diastolic pressure has been observed in the group with DIMA. In addition, significant correlation was observed between the thigh/arm index (expressing the perfusion through the ilicofemoral segment) and UPE (r = -0.464; p less than 0.001). This relationship persisted also in multivariate analysis where UPE was the only factor which entered the "best fit model". The results of the present study indicate that proteinuria might be a risk factor or a marker for proximal type of peripheral vascular disease in Type 2 diabetic mellitus.     

Renal disease as a risk factor for cardiovascular disease

Cardiovascular disease is the major cause of death in patients with endstage renal disease (ESRD). ESRD patients are almost invariably hypertensive. They all have acquired combined hyperlipidemia and increased Lp(a), hyperhomocysteinemia, decreased physical activity, pychosocial stress, insulin resistance, procoagulant factors, left ventricular hypertrophy, and increased oxidative stress. Diabetes mellitus, a major risk factor for both cardiovascular disease and ESRD, has become the commonest cause of ESRD. If ESRD patients choose to smoke, the additive risk is profound. Moreover, ESRD patients are becoming older and are often menopausal if female. Finally, ESRD patients have a dramatic tendency for vascular and cardiac calcification, probably related to hyperphosphatemia and hyperparathyroidism. Cardiovascular disease is also a major risk in patients with decreased renal function of nearly any degree. Data from the HDFP study showed that patients with a serum creatinine concentration > 1.5 mg/dl had a profoundly higher risk of cardiovascular disease than patients with creatinine values below this value. These data were recently corroborated in the HOPE study. Microalbuminuria (MAU), with or without diabetes mellitus, indicates increased cardiovascular disease risk even without decreases in glomerular filtration rate. We found earlier that nondiabetic hypertensive patients with MAU had much higher rates of myocardial infarction, stroke, and peripheral vascular disease, than similar hypertensive patients without MAU. In conclusion, the presence of decreased renal function or MAU is a major cardiovascular risk factor. ESRD can be regarded as a catastrophic risk factor. Prophylactic measures known to be effective in reducing the risk from cardiovascular disease are grossly underused. Unfortunately, they are less effective in patients with renal disease, and new strategies are needed.     

Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study

BACKGROUND: Previous studies examining the association of plasma cholesterol levels with the risk for development of Alzheimer disease (AD) have been inconclusive. We examined the impact of baseline and lifetime plasma total cholesterol levels averaged across many years on the risk for AD in a large, population-based cohort. METHODS: Five thousand two hundred nine subjects from the Framingham Study original cohort underwent biennial evaluation for cardiovascular risk factors since 1950, with estimations of serum total cholesterol levels at 19 of these 25 biennial examinations. The study sample consisted of 1026 subjects from this cohort who were alive and free of stroke and dementia at examination cycle 20 (1988-1989) and had undergone apolipoprotein E (APOE) genotyping. The main outcome measure was incident AD diagnosed using standard criteria, according to average total cholesterol levels across biennial examination cycles 1 to 15 and baseline total cholesterol level measured at the 20th biennial examination cycle. RESULTS: Alzheimer disease developed in 77 subjects from 1992 to 2000. After adjustment for age, sex, APOE genotype, smoking, body mass index (calculated as weight in kilograms divided by the square of height in meters), coronary heart disease, and diabetes, we found no significant association between the risk for incident AD and average cholesterol level at biennial examination cycles 1 to 15 (hazard ratio per 10-mg/dL [0.3-mmol/L] rise, 0.95; 95% confidence interval, 0.87-1.04) or baseline total cholesterol level at examination 20 (hazard ratio, 0.97; 95% confidence interval, 0.90-1.05). CONCLUSION: In this large, population-based cohort, baseline and long-term average serum total cholesterol levels were not associated with the risk for incident AD.     

Fasting lipids and anticardiolipin antibodies as risk factors for vascular disease in systemic lupus erythematosus.

Fasting cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apoprotein AI, and apoprotein B were measured in 64 patients with systemic lupus erythematosus to assess the risk factors for vascular disease. The relation between the lipid profile, steroid treatment, the presence of anticardiolipin antibodies, and the prevalence of vascular disease was examined. Raised concentrations of triglyceride and apoprotein B were seen in those patients treated with more than the equivalent of 10 mg prednisolone a day in the six months before testing. An increase in vascular disease was found only in the subgroup of patients with increased triglycerides who also expressed anticardiolipin antibodies. This study confirms the association between treatment with high doses of steroids in lupus and the development of an atherogenic plasma lipid profile. The presence of anticardiolipin antibodies compounds the risk of developing vascular disease.     

Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis

OBJECTIVE: Patients with systemic sclerosis (SSc) are at high risk for digital vascular complications, including amputation and gangrene. Cigarette smoking is an important risk factor for vascular disease in the general population. We investigated the influence of cigarette smoking on digital ischemia in patients with SSc. METHODS: We studied 101 patients with SSc (87 women and 14 men, median age 53 years, median disease duration 13 years). Smoking history was defined in terms of current smoking status and total number of pack-years. Digital ischemic events were classified as debridement, hospital admission for intravenous (IV) administration of vasodilators, and digital amputation. The influence of smoking on digital ischemic events was examined using logistic regression, adjusting for age, sex, and disease duration. Results are expressed as the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Of the 101 patients, 21 (21%) were current smokers, 37 (37%) were ex-smokers, and 43 (43%) had never smoked. After adjusting for age, sex, and disease duration, current smokers were significantly more likely than never-smokers to have had debridement (OR 4.5, 95% CI 1.1-18.3) or admission for IV vasodilators (OR 3.8, 95% CI 1.1-12.9). Patients smoking at higher intensity were more likely to require admission for IV vasodilators. CONCLUSION: Among patients with SSc, current smokers are 3-4 times more likely than never-smokers to incur digital vascular complications. Resources should be directed to supporting smoking cessation in patients with SSc.     

Augmentation index as a measure of peripheral vascular disease state

Pulse pressure, especially in central arteries, is an independent predictor of adverse cardiovascular events in patients with increased elastic artery stiffness (or elastance). The central arterial pressure wave is composed of a forward traveling wave generated by left ventricular ejection and a later arriving reflected wave from the periphery. Increased stiffness of elastic arteries is the primary cause of increased pulse pressure in subjects with degeneration and hyperplasia of the arterial wall. As stiffness increases, transmission velocity of both forward and reflected waves increase, which causes the reflected wave to arrive earlier in the central aorta and augments pressure in late systole [ie, augmentation index = (augmented pressure/pulse pressure) increases]. These changes in wave reflection properties are associated with vascular disease and aging and cause an increase in left ventricular afterload, myocardial mass, and oxygen consumption. Vasoactive drugs have little direct effect on large elastic arteries but can markedly change wave reflection amplitude and augmentation index by altering stiffness of the muscular arteries and modifying transmission velocity of the reflected wave from the periphery to the heart. This change in amplitude and timing of the reflected wave causes a generalized change in central arterial systolic and pulse pressure that is not detected by cuff pressure measurements in the brachial artery.