Impact of low-density lipoprotein cholesterol on cardiovascular outcomes in people with type 2 diabetes: A meta-analysis of prospective cohort studies

Aims

To estimate the prospective association of low-density lipoprotein (LDL) cholesterol on cardiovascular disease (CVD) risk among people with type 2 diabetes.

Methods

We used extensive literature searching strategies to locate prospective cohort studies that reported LDL cholesterol levels as a risk factor for cardiovascular events. We conducted meta-analytic procedures for two outcomes: incident CVD and CVD mortality.

Results

A total of 16 studies were included in this analysis with a mean follow-up range of 4.8–11 years. The pooled relative risk associated with a 1 mmol/L increase in LDL cholesterol in people with type 2 diabetes was 1.30 (95% confidence interval [CI], 1.19–1.43) for incident CVD, and 1.50 (95% CI, 1.25–1.80) for CVD mortality, respectively. Subgroup analyses showed that for incident CVD, the pooled relative risk was 1.28 (95% CI, 1.17–1.41) for 7 studies adjusted for blood pressure and/or glucose concentration (or insulin concentration, glycated hemoglobin) and 1.40 (95% CI, 1.05–1.86) for 3 studies that did not adjust for these variables.

Conclusions

Our study demonstrates that LDL cholesterol was associated with an increased risk for cardiovascular outcomes in people with type 2 diabetes, independent of other conventional risk factor.     

The metabolism of plant sterols is disturbed in postmenopausal women with coronary artery disease

In postmenopausal coronary artery disease (CAD) women, serum plant sterols are elevated. Thus, we investigated further whether serum plant sterols reflect absolute cholesterol metabolism in CAD as in other populations and whether the ABCG5 and ABCG8 genes, associated with plant sterol metabolism, were related to the risk of CAD. In free-living postmenopausal women with (n = 47) and without (n = 62) CAD, serum noncholesterol sterols including plant sterols were analyzed with gas-liquid chromatography, cholesterol absorption with peroral isotopes, absolute cholesterol synthesis with sterol balance technique, and bile acid synthesis with quantitating fecal bile acids. In CAD women, serum plant sterol ratios to cholesterol were 21% to 26% (P < .05) higher than in controls despite similar cholesterol absorption efficiency. Absolute cholesterol and bile acid synthesis were reduced. Only in controls were serum plant sterols related to cholesterol absorption (eg, sitosterol; in controls: r = 0.533, P < .001; in CAD: r = 0.296, P = not significant). However, even in CAD women, serum lathosterol (relative synthesis marker) and lathosterol-cholestanol (relative synthesis-absorption marker) were related to absolute synthesis and absorption percentage (P range from .05 to <.001) similarly to controls. Frequencies of the common polymorphisms of ABCG5 and ABCG8 genes did not differ between coronary and control women. In conclusion, plant sterol metabolism is disturbed in CAD women; so serum plant sterols only tended to reflect absolute cholesterol absorption. Other relative markers of cholesterol metabolism were related to the absolute ones in both groups. ABCG5 and ABCG8 genes were not associated with the risk of CAD.     

Effect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome

Objective

Metabolic syndrome (MetS) is associated with cardiovascular disease (CVD). Insulin resistance has been hypothesized as the underlying feature of MetS. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are widely used antihypertensives that may improve insulin sensitivity. The aim of the study is to evaluate the effect of ACEI/ARB on incident CVD events in older hypertensive patients with MetS.

Materials/Methods

We used the Cardiovascular Health Study, a prospective cohort study of individuals > 65 years of age to evaluate ACEI/ARB use and time to CVD events (including coronary and cerebrovascular events). The study included 777 subjects who had hypertension and ATP III-defined MetS, but free of CVD and diabetes at baseline. Cox regression models were used to evaluate the effect of ACEI/ARB as compared to other antihypertensives on the time to the first CVD events.

Results

ACEI/ARB use was associated with a decreased risk of CVD events (adjusted HR = 0.658, 95 % C.I. [0.436–0.993]) compared to other antihypertensives. When CVD endpoints were evaluated separately, use of ACEI/ARB was associated with lower rates of angioplasty and coronary events (HR of 0.129 and 0.530 respectively, with 95 % CI [0.017–0.952] and [0.321–0.875]).

Conclusions

ACEI/ARB use was associated with a lower risk of CVD events in older hypertensive patients with MetS, primarily due to a reduction in coronary events. The potential protective effect of ACEI/ARB on CVD events in older individuals with MetS will need further confirmation from prospective studies.     

Impact of lung‐function measures on cardiovascular disease events in older adults with metabolic syndrome and diabetes

Background

Individuals with metabolic syndrome (MetS) and diabetes (DM) are more likely to have decreased lung function and are at greater risk of cardiovascular disease (CVD).

Hypothesis.

Lung‐function measures can predict CVD events in older persons with MetS, DM, and neither condition.

Methods

We followed 4114 participants age ≥ 65 years with and without MetS or DM in the Cardiovascular Health Study. Cox regression examined the association of forced vital capacity (FVC) and 1‐second forced expiratory volume (FEV₁; percent of predicted values) with incident coronary heart disease and CVD events over 12.9 years.

Results

DM was present in 537 (13.1%) and MetS in 1277 (31.0%) participants. Comparing fourth vs first quartiles for FVC, risk of CVD events was 16% (HR: 0.84, 95% CI: 0.59–1.18), 23% (HR: 0.77, 95% CI: 0.60–0.99), and 30% (HR: 0.70, 95% CI: 0.58–0.84) lower in DM, MetS, and neither disease groups, respectively. For FEV₁, CVD risk was lower by 2% (HR: 0.98, 95% CI: 0.70–1.37), 26% (HR: 0.74, 95% CI: 0.59–0.93), and 31% (HR: 0.69, 95% CI: 0.57–0.82) in DM. Findings were strongest for predicting congestive heart failure (CHF) in all disease groups. C‐statistics increased significantly with addition of FEV₁ or FVC over risk factors for CVD and CHF among those with neither MetS nor DM.

Conclusions

FEV₁ and FVC are inversely related to CVD in older adults with and without MetS, but not DM (except for CHF); however, their value in incremental risk prediction beyond standard risk factors is limited mainly to metabolically healthier persons.     

Biliary lathosterol and other cholesterol precursor sterols are increased in patients with ileal exclusion

The human bile contains several noncholesterol sterols, of which the cholesterol precursor sterols are quantitatively the most important. Detailed data on factors that regulate the amount of these sterols in the bile have not been available. In this study the effect of chronic stimulation of cholesterol synthesis on biliary cholesterol precursor sterol content was evaluated by measuring these sterols in the bile and plasma of familial hypercholesterolemia patients with and without ileal exclusion. In the operated patients cholesterol synthesis was fivefold increased, and cholesterol precursor sterols comprised 7% of the biliary sterols, compared with 2% in the control patients. All eight biliary cholesterol precursor sterols measured were significantly increased in the operated patients, and the increase was similar to that of respective sterols in plasma. Hence, the biliary methyl sterols were increased 2 to 4 times, the lathosterols 5 times, but demosterol only 1.5 times. The proportion of lathosterol was higher and that of lanosterol lower in the bile of the operated than in that of the control patients. We conclude that activation of cholesterol synthesis increases the amount of cholesterol precursor sterols in the bile in proportion to the increase of these sterols in plasma and to the overall cholesterol synthesis.     

Prevalence of obesity and associated risk factors in Northeastern China

Aim

To investigate the prevalence of obesity and associated risk factors in the Northeastern Chinese city of Dehui.

Methods

A cross-sectional study involving random sampling methods generated 3598 completed questionnaires by permanent residents of Dehui. Binary multivariate logistic regression analysis was used to identify factors that were significantly associated with obesity.

Results

Based on the 2000 WHO diagnostic criterion regarding populations in the Asia-Pacific region, the prevalence of obesity was 37.71% (34.77% of females; 41.11% of males). Elevated body mass index (BMI) was significantly associated with cardiovascular disease (CVD)-associated conditions (P < 0.05), and increased prevalence of abnormally high transaminase levels (P < 0.05). Binary logistic regression analysis demonstrated the following variables were associated with obesity: increased age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: 1.0-1.02), high total cholesterol (TC) (OR: 1.26, 95% CI: 1.03-1.54), high triglycerides (TG) (OR: 1.38, 95% CI: 1.16-1.64), hypertension (OR: 1.62, 95% CI: 1.39-1.90), fatty liver (OR: 2.91, 95% CI: 2.41-3.49), living in an urban setting (OR: 2.84, 95% CI: 2.39-3.38), and advanced education (OR: 1.22, 95% CI: 1.06-1.40).

Conclusions

Obesity is prevalent among the adult population in Northeastern China and is significantly associated with CVD risk factors such as hypertension, dyslipidemia, as well as transaminase abnormalities.     

Metabolically Healthy Obesity,Transition to Metabolic Syndrome,and Cardiovascular Risk

Background

Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal follow-up, with inconsistent results.

Increased levels of microparticles originating from endothelial cells, platelets and erythrocytes in subjects with metabolic syndrome: Relationship with oxidative stress

Background and aims

The Metabolic Syndrome (MetS) is associated with increased cardiovascular risk. Circulating microparticles (MP) are involved in the pathogenesis of atherothrombotic disorders and are raised in individual with CVD. We measured their level and cellular origin in subjects with MetS and analyzed their associations with 1/anthropometric and biological parameters of MetS, 2/inflammation and oxidative stress markers.

Methods and results

Eighty-eight subjects with the MetS according to the NCEP-ATPIII definition were enrolled in a bicentric study and compared to 27 healthy controls. AnnexinV-positive MP (TMP), MP derived from platelets (PMP), erythrocytes (ErMP), endothelial cells (EMP), leukocytes (LMP) and granulocytes (PNMP) were determined by flow cytometry. MetS subjects had significantly higher counts/μl of TMP (730.6 ± 49.7 vs 352.8 ± 35.6), PMP (416.0 ± 43.8 vs 250.5 ± 23.5), ErMP (243.8 ± 22.1 vs 73.6 ± 19.6) and EMP (7.8 ± 0.8 vs 4.0 ± 1.0) compared with controls. LMP and PNMP were not statistically different between groups. Multivariate analysis demonstrated that each criterion for the MetS influenced the number of TMP. Waist girth was a significant determinant of PMP and EMP level and blood pressure was correlated with EMP level. Glycemia positively correlated with PMP level whereas dyslipidemia influenced EMP and ErMP levels. Interestingly, the oxidative stress markers, plasma glutathione peroxydase and urinary 8-iso-prostaglandin F₂ α, independently influenced TMP and PMP levels whereas inflammatory markers did not, irrespective of MP type.

Conclusion

Increased levels of TMP, PMP, ErMP and EMP are associated with individual metabolic abnormalities of MetS and oxidative stress. Whether MP assessment may represent a marker for risk stratification or a target for pharmacological intervention deserves further investigation.     

Apolipoprotein E genotype is not associated with cardiovascular disease in heterozygous subjects with familial hypercholesterolemia

Background

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). There are important differences in the presence of CVD among heterozygous subjects with FH. Some of this variability can be explained by genetic factors, and the apolipoprotein (apo) E genotype has been proposed as a useful marker.

Methods

We analyzed the apo E genotype in 706 non-related subjects who were heterozygous for FH from Spain. CVD was present in 198 subjects (28%), 132 men (41%) and 66 women (17%).

Results

Apo E allele frequencies for the ε3, ε4, and ε2 alleles were 0.89, 0.09, and 0.02 respectively. Age, body mass index, smoking status, high blood pressure, diabetes mellitus, presence of tendon xanthomas, total cholesterol level, triglyceride levels, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, and Lp(a) did not differ among genotypes. The incidence of CVD and the age of onset of CVD did not differ among genotypes either. In the multivariant analysis, apo E genotype did not contribute significantly to CVD.

Conclusions

Heterozygous men with FH have a very high risk of coronary disease in a Mediterranean country, and the apo E genotype in this large group of adults with FH is not associated either with CVD or lipid values, in contrast with the established effect in the general population.     

Does a Mediterranean diet reduce the mortality risk associated with diabetes: evidence from the Melbourne Collaborative Cohort Study

Background and aims

Diabetes is a risk factor for cardiovascular disease (CVD), yet southern European migrants to Australia with high rates of type 2 diabetes have relatively low CVD mortality. Our aim was to determine whether a Mediterranean style diet could reduce mortality in people with diabetes.

Methods and results

Participants included 16,610 males and 23,860 females from the Melbourne Collaborative Cohort Study; 25% were born in Greece or Italy, and 2150 had previously been diagnosed with diabetes or had elevated blood glucose at baseline (1990-94). Data on demographic, behavioral and physical risk factors were also collected. A personal Mediterranean Diet Score (MDS) was calculated using data from a validated 121-item food frequency questionnaire. Total and CVD mortality data were available up to 2003.Diabetes (new and known) at baseline, was associated with total mortality (men HR 1.43, 95%CI 1.26-1.62; women HR 1.86 95%CI 1.58-2.18), and CVD mortality (men HR 1.53, 95%CI 1.21-1.94; women HR 2.10 95%CI 1.48-2.97) in multivariate models. There was no evidence that glucose tolerance modified the associations between MDS and total or CVD mortality (p interaction all > 0.16). The HRs for total mortality per unit of MDS were 0.96 (95% CI 0.93-0.99) in men and 0.94 (95% CI 0.92-0.97) in women. The HRs for CVD mortality per unit of MDS were 0.94 (95% CI 0.89-0.99) in men and 0.94 (95% CI 0.87-1.01) in women.

Conclusion

Our results add to the evidence supporting the benefit of a Mediterranean style diet for people with type 2 diabetes.     

Inverse association between fruit, legume, and cereal fiber and the risk of metabolic syndrome: Tehran Lipid and Glucose Study

Aims

To evaluate the association between total dietary fiber and its types and sources with the risk of MetS.

Methods

This population-based cross-sectional study was conducted on a representative sample of 2 457 adults (1 327 male and 1 130 female), aged 19-84 years. Dietary intake was assessed using a validated semiquantitative food-frequency questionnaire. Anthropometrics, blood pressure, and fasting blood glucose and lipids were measured according to standard protocols. The MetS was defined according to definition by Adult Treatment Panel III.

Results

Multivariate-adjusted odds ratio of MetS between highest and lowest quartiles was 0.53 (95% CI: 0.39-0.74; P for trend <0.05) for total dietary fiber, 0.60 (0.43-0.84; P for trend <0.05) for soluble fiber, and 0.51 (0.35-0.72; P for trend <0.05) for insoluble fiber. Among sources of dietary fiber, fruit fiber (OR: 0.51; 95% CI: 0.37-0.72), cereal fiber (0.74; 0.57-0.97), and legume fiber (0.73; 0.53-0.99) were inversely associated with the risk of MetS, after adjustment for confounding factors. Intake of vegetable fiber and nut fiber were unrelated to the risk of MetS.

Conclusions

Total dietary fiber, soluble- and insoluble fiber, fruit fiber, cereal fiber and legume fiber were associated with a protective effect for the presence of MetS among this Tehranian population.     

Diabetic retinopathy is associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus

Aims

We aimed to evaluate the association between diabetic microangiopathy and subclinical atherosclerosis as a marker of cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes.

Methods

A total of 142 newly diagnosed type 2 diabetics who were free from CVD underwent evaluation of diabetic microangiopathy. Subclinical atherosclerosis was assessed by measuring carotid intima-media thickness (IMT), and the 10-year absolute risk of CVD was estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine.

Results

Subclinical atherosclerosis was found in 27 subjects (19.0%). The rates of hypertension and diabetic retinopathy were significantly higher among patients with subclinical atherosclerosis. The UKPDS 10-year risk for CVD was significantly increased in subjects with subclinical atherosclerosis. Old age, hypertension and the presence of diabetic retinopathy showed a significant association to subclinical atherosclerosis after further adjustments for gender, body mass index, smoking status, HbA1c, HDL cholesterol, LDL cholesterol and the presence of diabetic nephropathy.

Conclusions

This study shows that diabetic retinopathy is an independent risk marker for subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. We suggest that a diagnosis of diabetic retinopathy may warrant a more careful cardiovascular assessment even in the early stages of diabetes.     

Metabolic syndrome vs. its components for prediction of cardiovascular mortality: A cohort study in Chinese elderly adults

Objectives The predictive value of the metabolic syndrome (MetS) for mortality from all-cause and cardiovascular disease (CVD) in the Chinese population is unclear. The aim of this present study was to compare MetS with its individual components as predictors of mortality in Chinese elderly adults. Methods A cohort of 1,535 subjects (994 men and 541 women) aged 50 years or older was selected from employees of a machinery factory in 1994 and followed until 2009. Cox models were used to estimate the hazard ratios (HRs) predicted by MetS according to the harmonized definition and by its individual components. Results The baseline prevalence of MetS was 28.0% in men and 48.4% in women. During a median follow-up of 15 years, 414 deaths occurred, of these, 153 participants died from CVD. Adjusted for age and gender, the HRs of mortality from all-cause and CVD in participants with MetS were 1.47 (95% confidence interval (CI): 1.20–1.80) and 1.96 (95%CI: 1.42–2.72), respectively, compared with those without MetS. Non-significant higher risk of CVD mortality was seen in those with one or two individual components (HR = 1.22, 95%CI: 0.59–2.50; HR = 1.82, 95%CI: 0.91–3.64, respectively), while a substantially higher risk of CVD mortality only appeared in those with 3, 4, or 5 components (HR = 2.81–3.72), compared with those with no components. On evaluating the MetS components individually, we found that, independent of MetS, only hypertension and impaired glucose predicted higher mortality. Conclusions The number of positive MetS components seems no more informative than classifying (dichotomous) MetS for CVD risks assessment in this Chinese cohort.     

Applicability of non-cholesterol sterols in predicting response in cholesterol metabolism to simvastatin and fluvastatin treatment among hypercholesterolemic men

Background and aimsWe hypothesized that (I) certain features in cholesterol metabolism at baseline could predict a response to statins, (II) good and poor responders to statins have a differential profile of serum and fecal sterols and (III) serum non-cholesterol sterols reflect cholesterol metabolism on statins.Methods and resultsWe examined serum lipids, serum and fecal cholesterol, cholesterol precursors, cholestanol and phytosterols and cholesterol metabolism among 20 hypercholesterolemic men at baseline and on 16-wk simvastatin/fluvastatin treatment.At baseline, the mean of serum cholestanol/cholesterol was 11% lower but those of lathosterol/cholesterol, lathosterol/cholestanol, desmosterol/cholesterol, desmosterol/cholestanol were 36–65% higher among good than poor responders (p < 0.05 for each). On statins, reductions in ratios of serum precursor sterols and increases of absorption sterols were 1.8–2.9 times higher among good than poor responders (p < 0.05 for each). In the whole study group, changes from baseline values of lathosterol/cholestanol were related to those of cholesterol and LDL-C in serum (r = +0.513 and +0.451, p = 0.021 and 0.046, respectively). Serum lathosterol ratios to cholesterol, cholestanol and sitosterol consistently reflected a ratio of cholesterol synthesis (mg/d/kg)/fractional cholesterol absorption (%) (r-range +0.456 to +0.727, p < 0.05 for each).ConclusionsLow serum baseline ratios to cholesterol of lathosterol, cholestenol and desmosterol, but a high ratio of cholestanol predicted a poor response to statins. Good responders were characterized by more profound reductions of serum and fecal (lathosterol) precursor sterols and increases of serum absorption marker sterol ratios on statins. Serum surrogate sterol markers of cholesterol metabolism were applicable in evaluating cholesterol absorption and synthesis also on statins.     

Non-cholesterol sterols in serum and endarterectomized carotid arteries after a short-term plant stanol and sterol ester challenge

Background and Aims

It is not known whether dietary intake of plant stanols or sterols changes the composition of arterial sterols. Therefore, we compared serum and carotid artery cholesterol and non-cholesterol sterols after plant stanol (staest) or sterol (steest) ester feeding in endarterectomized patients.

Methods and Results

Elderly statin-treated asymptomatic patients undergoing carotid endarterectomy were randomized double-blind to consume staest (n = 11) or steest (n = 11) spread (2 g of stanol or sterol/day) for four weeks preoperatively. Non-cholesterol sterols from serum and carotid artery tissue were analysed with gas-liquid chromatography. Staest spread lowered serum total (17.2%), VLDL, and LDL cholesterol and serum triglycerides, while steest spread lowered serum total (13.8%) and LDL cholesterol levels from baseline (p < 0.05 for all). Serum cholestanol and avenasterol were decreased in both groups, but campesterol and sitosterol were decreased by staest and increased by steest from baseline (p < 0.05 from baseline and between the groups). Serum sitostanol to cholesterol ratio was increased by staest, but in arterial tissue this ratio was similar in both groups. On staest, lathosterol, campesterol, and sitosterol, and on steest sitosterol and avenasterol correlated significantly between serum and arterial tissue. Cholesterol metabolism, eg. lathosterol/campesterol, suggested that plant sterols were reduced in serum and in arterial tissue during staest.

Conclusion

The novel observations were that plant stanol ester consumption, in contrast to plant sterols, tended to reduce carotid artery plant sterols in statin-treated patients. Furthermore, despite increased serum sitostanol contents during plant stanol ester consumption, their arterial levels were unchanged suggesting that sitostanol is not taken up into the arterial wall.     

Do apolipoproteins improve coronary risk prediction in subjects with metabolic syndrome? Insights from the North Italian Brianza cohort study

Objective

We assessed predictive abilities and clinical utility of CVD risk algorithms including ApoB and ApoAI among non-diabetic subjects with metabolic syndrome (MetS).

Methods

Three independent population-based cohorts (3677 35–74 years old) were enrolled in Northern Italy, adopting standardized MONICA procedures. Through Cox models, we assessed the associations between lipid measures and first coronary events, as well as the changes in discrimination and reclassification (NRI) when standard lipids or apolipoproteins were added to the CVD risk algorithm including non-lipids risk factors. Finally, the best models including lipids or apolipoproteins were compared.

Results

During the 14.5 years median follow-up time, 164 coronary events were validated. All measures showed statistically significant associations with the endpoint, while in the MetS subgroup HDL-C and ApoAI (men, HR = 1.59; 95%CI: 0.96–2.65) were not associated. Models including HDL-C plus TC and ApoB plus ApoAI for lipids and apolipoproteins, respectively, showed the best predictive values. When ApoB plus ApoAI replaced TC plus HDL-C, NRI values improved in subjects with MetS (13.8; CI95%: −5.1,53.1), significantly in those previously classified at intermediate risk (44.5; CI95% 13.8,129.6). In this subgroup, 5.5% of subjects was moved in the high (40.0% of expected events) and 17.0% in the low risk class (none had an event at 10 years).

Conclusions

ApoB and ApoAI could improve coronary risk prediction when used as second level biomarkers in non-diabetic subjects with MetS classified at intermediate risk. The absence of cases moved downward suggests the gain in avoiding treatments in non-cases and favor the use of apolipoproteins for risk assessment.     

Adherence to dietary guidelines and cardiovascular disease risk in the EPIC-NL cohort

Background

Global and national dietary guidelines have been created to lower chronic disease risk. The aim of this study was to assess whether greater adherence to the WHO guidelines (Healthy Diet Indicator (HDI)); the Dutch guidelines for a healthy diet (Dutch Healthy Diet-index (DHD-index)); and the Dietary Approaches to Stop Hypertension (DASH) diet was associated with a lower risk of cardiovascular disease (CVD), coronary heart disease (CHD) or stroke.

Methods

A prospective cohort study was conducted among 33,671 healthy Dutch men and women aged 20–70 years recruited into the EPIC-NL study during 1993–1997. We used Cox regression adjusted for relevant confounders to estimate the hazard ratios per standard deviation increase in score and 95% confidence intervals (CI) of the associations between the dietary guidelines and CVD, CHD and stroke risk.

Results

After an average follow-up of 12.2 years, 2752 CVD cases were documented, including 1630 CHD cases and 527 stroke cases. We found no association between the HDI (0.98, 95% CI 0.94; 1.02) or DHD-index (0.96, 95% CI 0.92; 1.00) and CVD incidence. Similar results were found for these guidelines and CHD or stroke incidence. Higher adherence to the DASH diet was significantly associated with a lower CVD (0.92, 95% CI 0.89; 0.96), CHD (0.91, 95% CI 0.86; 0.95), and stroke (0.90, 95% CI 0.82; 0.99) risk.

Conclusion

The HDI and the DHD-index were not associated with CVD risk, while the DASH diet was significantly associated with a lower risk of developing CVD, CHD and stroke.     

Normal fasting plasma glucose and risk of type 2 diabetes diagnosis

Purpose

The study compares the risk of incident diabetes associated with fasting plasma glucose levels in the normal range, controlling for other risk factors.

Methods

We identified 46,578 members of Kaiser Permanente Northwest who had fasting plasma glucose levels less than 100 mg/dL between January 1, 1997, and December 31, 2000, and who did not previously have diabetes or impaired fasting glucose. After assigning subjects to 1 of 4 categories (<85, 85-89, 90-94, or 95-99 mg/dL), we followed them until they developed diabetes, died, or left the health plan, or until April 30, 2007. We used Cox regression analysis to estimate the risk of incident diabetes, adjusted for age, sex, body mass index, blood pressure, lipids, smoking, cardiovascular disease, and hypertension.

Results

Subjects developed diabetes at a rate of less than 1% per year during a mean follow-up of 81.0 months. Each milligram per deciliter of fasting plasma glucose increased diabetes risk by 6% (hazard ratio [HR] 1.06, 95% confidence interval [CI], 1.05-1.07, P < .0001) after controlling for other risk factors. Compared with those with fasting plasma glucose levels less than 85 mg/dL, subjects with glucose levels of 95 to 99 mg/dL were 2.33 times more likely to develop diabetes (HR 2.33; 95% CI, 1.95-2.79; P < .0001). Subjects in the 90 to 94 mg/dL group were 49% more likely to progress to diabetes (HR 1.49; 95% CI, 1.23-1.79; P <.0001). All other risk factors except sex were significantly associated with a diabetes diagnosis.

Conclusions

The strong independent association between the level of normal fasting plasma glucose and the incidence of diabetes after controlling for other risk factors suggests that diabetes risk increases as fasting plasma glucose levels increase, even within the currently accepted normal range.     

Type 2 diabetes does not attenuate racial differences in coronary calcification

Aims

Coronary artery calcification (CAC) is a strong predictor of atherosclerotic cardiovascular disease (CVD). Whites appear to have a higher prevalence of CAC than African-Americans (AAs), but it is unknown if type 2 diabetes, a major cardiovascular risk factor, attenuates this difference. We investigated the relationship of race and CAC in a sample of patients with type 2 diabetes without clinical CVD.

Methods

Multivariable analyses of self-reported ethnicity and CAC scores, stratified by gender, in 861 subjects [32% AA, 66.9% male] with type 2 diabetes.

Results

AA race was associated with lower CAC scores in age-adjusted models in males [Tobit ratio for AAs vs. Whites 0.14 (95% CI 0.08-0.24, p < 0.001)] and females [Tobit ratio 0.26 (95% CI 0.09-0.77, p = 0.015)]. This persisted in men after adjustment for traditional, metabolic and inflammatory risk factors, but adjustment for plasma triglycerides [0.48 (95% CI 0.15-1.49, p = 0.201)] and HOMA-IR [0.28 (95% CI 0.08-1.03, p = 0.055)] partially attenuated the association in women.

Conclusions

Relative to African-Americans, White race is a strong predictor of CAC, even in the presence of type 2 diabetes. The relationship in women appears less robust possibly due to gender differences in metabolic risk factors.     

Is serum cystatin-C a reliable marker for metabolic syndrome?

Purpose

Chronic kidney disease and metabolic syndrome are recognized as major cardiovascular risk factors. It has been shown that cystatin C has a stronger association with mortality risk than creatinine-based estimations of glomerular filtration rate. We measured cystatin values in dyslipidemic patients and looked for correlations between renal function, cystatin, and metabolic syndrome.

Methods

There were 925 dyslipidemic patients prospectively included in this cross-sectional study and evaluated over 10 months. Each visit included clinical and biological assessment.

Results

Most patients exhibited cardiovascular risk factors other than dyslipidemia: hypertension in 34%, diabetes in 11%, and smoking in 18%. Mean triglycerides were 149 ± 136 mg/dL, mean high-density lipoprotein cholesterol 54 ± 14 mg/dL, and low-density lipoprotein 167 ± 48 mg/dL. Metabolic syndrome was present in 238 (26%) patients. Plasma creatinine did not differ between control group and metabolic syndrome patients (80 ± 26 vs 82 ± 20 μmol/L, respectively, P = .2), but creatinine clearance evaluated by abbreviated Modification of Diet in Renal Disease Study formula was lower in the metabolic syndrome group than in the non-metabolic-syndrome group (83.3 ± 18.8 mL/min/1.73m² vs 86.8 ± 16.9 mL/min/1.73m², respectively, P <.007). Cystatin value was significantly higher in metabolic syndrome patients than in others (0.86 ± 0.23 vs 0.79 ± 0.20 mg/L, respectively, P <.0001), independently of serum creatinine level and creatinine clearance. Furthermore, there was a progressive increase in cystatin, as a function of the number of metabolic syndrome components.

Conclusions

Our study shows that cystatin is associated with metabolic syndrome in dyslipidemic patients. Cystatin may be an interesting marker of metabolic syndrome and of increased cardiovascular and renal risk.