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• Inclisiran lowers LDL-C by -38 % at 3 months in real-world setting. • Patients who use statin co-medication had a greater LDL-C reduction of -45 %. • Most patients switching from PCSK9 mAbs to inclisiran showed an increase in LDL-C. • Inclisiran has a favourable safety profile in real-world setting at 3 and 9 months follow-up. Inclisiran is the first-in-class small interfering RNA (siRNA) proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor. In clinical trials inclisiran showed effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction of ± 50 %. As data in clinical setting are scarce, we aim to investigate the efficacy and safety in clinical practice. We describe a registry of consecutive patients who started with inclisiran at a lipid clinic of a university hospital. Patients were eligible if they fulfilled the reimbursement criteria in the Netherlands. Patients were included if they started with inclisiran as first line (group 1) or switched from PCSK9 monoclonal antibody (mAbs) to inclisiran (group 2). LDL-C levels were measured at 3 and 9 months after initiation of inclisiran. Median change of LDL-C levels was calculated on an individual and group level. We analysed 65 patients (36 women), median [25th percentile; 75th percentile] age of 63 [54; 68] years. Of these, 44 patients had both a 3 month and 9 month visit. At 3 months, patients who newly started inclisiran (group 1, n = 45) showed a LDL-C decrease of 38 [-49;-33] %. Patients who used statins as co-medication (n = 15) had a higher median LDL-C decrease compared to those without statin use (n=30; 45 % vs 38 %). However, patients who switched from mAbs to inclisiran (group 2, n = 20) had an increase in LDL-C of 38 [+4; +97] %. Adverse effects associated with inclisiran were mild and consisted of mild injection site reactions. Efficacy was slightly less whereas safety results were similar at 9 months. Our initial experience of inclisiran in a clinical setting showed less reduction in LDL-C levels compared to clinical trials but a similar safety profile. Moreover, patients who switched from PCSK9 mAbs to inclisiran generally showed an increase in LDL-C levels implying that inclisiran is less potent in LDL-C reduction compared to PCSK9 mAbs. [Display omitted] [ABSTRACT FROM AUTHOR]

• In FD, PCSK9 mAbs in particular reduce smaller and cholesterol-rich lipoproteins. • PCSK9 mAbs do not affect CM metabolism. • PCSK9 mAbs probably achieve their effects by increased hepatic clearance. Proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibodies (mAbs) reduce fasting and post fat load cholesterol in non-HDL and intermediate density lipoprotein (IDL) in familial dysbetalipoproteinemia (FD). However, the effect of PCSK9 mAbs on the distribution and composition of atherogenic lipoproteins in patients with FD is unknown. To evaluate the effect of the PCSK9 mAb evolocumab added to standard lipid-lowering therapy in patients with FD on fasting and post fat load lipoprotein distribution and composition. Randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. Patients received an oral fat load at the start and end of each treatment period. Apolipoproteins (apo) were measured with ultracentrifugation, gradient gel electrophoresis, retinyl palmitate and SDS-PAGE. PCSK9 mAbs significantly reduced particle number of all atherogenic lipoproteins, with a stronger effect on smaller lipoproteins than on larger lipoproteins (e.g. IDL-apoB 49%, 95%confidence interval (CI) 41–59 and very low-density lipoprotein (VLDL)-apoB 33%, 95%CI 16-50). Furthermore, PCSK9 mAbs lowered cholesterol more than triglyceride (TG) in VLDL, IDL and low-density lipoprotein (LDL) (e.g. VLDL-C 48%, 95%CI 29–63%; and VLDL-TG 20%, 95%CI 6.3–41%). PCSK9 mAbs did not affect the post fat load response of chylomicrons. PCSK9 mAbs added to standard lipid-lowering therapy in FD patients significantly reduced lipoprotein particle number, in particular the smaller and more cholesterol-rich lipoproteins (i.e. IDL and LDL). PCSK9 mAbs did not affect chylomicron metabolism. It seems likely that the observed effects are achieved by increased hepatic lipoprotein clearance, but the specific working mechanism of PCSK9 mAbs in FD patients remains to be elucidated. [Display omitted] [ABSTRACT FROM AUTHOR]

• In familial dysbetalipoproteinemia (FD), evolocumab reduced non-HDL-C by 49%. • Non-HDL-C treatment goals were achieved by 89% of patients using evolocumab. • Evolocumab likely results in CVD reduction in FD. Familial dysbetalipoproteinemia (FD) is the second most common monogenic lipid disorder (prevalence 1 in 850-3500), characterized by postprandial remnant accumulation and associated with increased cardiovascular disease (CVD) risk. Many FD patients do not achieve non-HDL-C treatment goals, indicating the need for additional lipid-lowering treatment options. To evaluate the effect of the PCSK9 monoclonal antibody evolocumab added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in patients with FD. A randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. At the start and end of each treatment period patients received an oral fat load. The primary endpoint was the 8-hour post fat load non-HDL-C area under the curve (AUC). Secondary endpoints included fasting and post fat load lipids and lipoproteins. In total, 28 patients completed the study. Mean age was 62±9 years and 93% had an Ɛ2Ɛ2 genotype. Evolocumab reduced the 8-hour post fat load non-HDL-C AUC with 49% (95%CI 42-55) and apolipoprotein B (apoB) AUC with 47% (95%CI 41-53). Other fasting and absolute post fat load lipids and lipoproteins including triglycerides and remnant-cholesterol were also significantly reduced by evolocumab. However, evolocumab did not have significant effects on the rise above fasting levels that occurred after consumption of the oral fat load. Evolocumab added to standard lipid-lowering therapy significantly reduced fasting and absolute post fat load concentrations of non-HDL-C, apoB and other atherogenic lipids and lipoproteins in FD patients. The clinically significant decrease in lipids and lipoproteins can be expected to translate into a reduction in CVD risk in these high-risk patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Despite lipid-lowering therapy (LLT), some patients with familial hypercholesterolemia (FH) still develop cardiovascular events. Data about the quantification and factors contributing to this residual risk are lacking. Objective This study assessed how many patients with FH developed a cardiovascular event despite LLT and which factors contribute to this risk. Methods We performed a time-dependent analysis in a cohort of consecutive heterozygous FH patients using stable LLT to evaluate first and subsequent cardiovascular events. Univariate and multivariate regression analyses were conducted to study the association between clinical characteristics and cardiovascular events. Results Of 821 FH patients (median age 47.4 [interquartile range (IQR) 35.3–58.3] years) treated with LLT for a median period of 9.5 (IQR 5.1–14.2) years, 102 patients (12%) developed cardiovascular disease (CVD) in 8538 statin-treated person-years. Patients who developed a cardiovascular event had a median age of 52.0 (IQR 43.8–59.3) years. These patients more often had previous cardiovascular events (32% vs 9%, P < .001), a family history of premature CVD (58% vs 40%, P = .001), hypertension (70% vs 22%, P < .001), higher on-treatment low-density lipoprotein cholesterol (162 ± 54 vs 135 ± 58 mg/dL, P < .001), lower on-treatment high-density lipoprotein cholesterol (50 ± 15 vs 54 ± 15 mg/dL, P < .001), and were smokers (32% vs 14%, P < .001), compared to patients without cardiovascular events. In 31 patients (30%), a subsequent cardiovascular event occurred with a median interval of 5.7 (IQR 2.4–9.3) years between events. They were more often smokers (32% vs 10%, P = .01) compared to patients with a single cardiovascular event. Conclusions Despite LLT, FH patients still develop cardiovascular events and especially subsequent events. Classical risk factors such as smoking and hypertension are driving factors for this risk, indicating the high priority of optimizing risk factor reduction in addition to maximum LLT. [ABSTRACT FROM AUTHOR]

Preeclampsia increases the long-term risk of cardiovascular disease, possibly through occurrence of hypertension after delivery, such as masked hypertension, night-time hypertension, and an adverse systolic night-to-day blood pressure (BP) ratio. These types of hypertension are often unnoticed and can only be detected with ambulatory BP monitoring (ABPM). We aimed to determine hypertension prevalence and 24-hour BP pattern with ABPM and office BP measurements in women 1 year after severe preeclampsia. This is a retrospective cohort study. As part of a follow-up program after severe preeclampsia, 200 women underwent ABPM and an office BP measurement 1 year after delivery. We calculated hypertension prevalence (sustained hypertension, masked hypertension, and white-coat hypertension) and systolic night-to-day BP ratio (dipping pattern). Medical files and questionnaires provided information on preexisting hypertension and antihypertensive treatment. One year after delivery, 41.5% of women had hypertension (sustained hypertension, masked hypertension, or white-coat hypertension) with ABPM. Masked hypertension was most common (17.5%), followed by sustained hypertension (14.5%) and white-coat hypertension (9.5%). With sheer office BP measurement, only 24.0% of women would have been diagnosed hypertensive. Forty-six percent of women had a disadvantageous dipping pattern. Hypertension is common 1 year after experiencing severe preeclampsia. Masked hypertension and white-coat hypertension are risk factors for future cardiovascular disease and can only be diagnosed with ABPM. Therefore, ABPM should be offered to all these women at high risk of developing hypertension and possibly future cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background Despite optimal lipid-lowering therapy, a minority of patients with familial hypercholesterolemia (FH) reach low-density lipoprotein cholesterol (LDL-c) target goals. In randomized trials, proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors led to impressive LDL-c reductions and a favorable safety profile. However, data about the efficacy and safety outside clinical trials are not available yet. Objective The purpose of the study is to describe efficacy and side effects of PCSK9 inhibitors in FH patients in clinical practice. Methods Registry of all consecutive FH patients who started with a PCSK9 inhibitor at a lipid clinic of a university hospital. Results We analyzed 83 FH patients (79 heterozygous FH [heFH]—65 with a genetically confirmed heFH and 14 with clinical heFH—and 4 homozygous FH [hoFH]), with a mean age of 55.1 ± 11.6 years. Treatment with a PCSK9 inhibitor resulted in an additional reduction of 55% ± 21% in mean LDL-c levels. Patients with heFH had more LDL-c decrease than those with hoFH (56% vs 38%). Patients using ezetimibe monotherapy because of statin intolerance (n = 24, 29%) had less LDL-c decrease compared with patients who concurrently used statin therapy (47% and 58%, P = .03). Side effects of PCSK9 inhibitors were reported by 32 patients (39%). Flu-like symptoms (n = 12) and injection site reactions (n = 11) were most frequent. Seven patients (8%) discontinued treatment, 5 because of side effects and 2 because of nonresponse. Conclusion Our initial experience of PCSK9 inhibition in FH patients in a clinical setting showed comparable reduction in LDL-c levels but more side effects compared with clinical trials. [ABSTRACT FROM AUTHOR]

Background Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor ( LDLR ), apolipoprotein B ( APOB ), or proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) are characterized by high low-density lipoprotein cholesterol levels and in some studies also high lipoprotein(a) (Lp(a)) levels were observed. The question remains whether this effect on Lp(a) levels is gene-dose–dependent in individuals with either 0, 1, or 2 LDLR or APOB mutations. Objective We set out to study whether Lp(a) levels differ among bi-allelic ADH mutation carriers, and their relatives, in the Netherlands. Methods Bi-allelic ADH mutation carriers were identified in the database of the national referral laboratory for DNA diagnostics of inherited dyslipidemias. Family members were invited by the index cases to participate. Clinical parameters and Lp(a) levels were measured in bi-allelic ADH mutation carriers and their heterozygous and unaffected relatives. Results We included a total of 119 individuals; 34 bi-allelic ADH mutation carriers (20 homozygous/compound heterozygous LDLR mutation carriers (HoFH), 2 homozygous APOB mutation carriers (HoFDB), and 12 double heterozygotes for an LDLR and APOB mutation), 63 mono-allelic ADH mutation carriers (50 heterozygous LDLR [HeFH], 13 heterozygous APOB [HeFDB] mutation carriers), and 22 unaffected family members. Median Lp(a) levels in unaffected relatives, HeFH, and HoFH patients were 19.9 (11.1–41.5), 24.4 (5.9–70.6), and 47.3 (14.9–111.7) mg/dL, respectively ( P = .150 for gene-dose dependency). Median Lp(a) levels in HeFDB and HoFDB patients were 50.3 (18.7–120.9) and 205.5 (no interquartile range calculated), respectively ( P = .012 for gene-dose-dependency). Double heterozygous carriers of LDLR and APOB mutations had median Lp(a) levels of 27.0 (23.5–45.0), which did not significantly differ from HoFH and HoFDB patients ( P = .730 and .340, respectively). Conclusion A (trend toward) increased plasma Lp(a) levels in homozygous ADH patients compared with both heterozygous ADH and unaffected relatives was observed. Whether increased Lp(a) levels in homozygous ADH patients add to the increased cardiovascular disease risk and whether this risk can be reduced by therapies that lower both low-density lipoprotein cholesterol and Lp(a) levels remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure one to three years after a premenopausal oophorectomy. However, the long-term effects of a premenopausal oophorectomy on sexual functioning are unknown.Objective: Our aim was to study long-term sexual functioning in women at increased familial risk of breast/ovarian cancer who underwent a risk-reducing salpingo-oophorectomy either before the age of 46 years (premenopausal group), or after the age of 54 years (postmenopausal group). We performed subgroup analyses in the premenopausal group, comparing early (before the age of 41 years) and later (at ages 41-45 years) premenopausal risk-reducing salpingo-oophorectomy.Study Design: Between 2018 and 2021, we invited 817 women with a high familial risk of breast/ovarian cancer from an ongoing cohort study to participate in our study. Due to a large difference in age at study between the premenopausal and postmenopausal salpingo-oophorectomy groups, we restricted the comparison of sexual functioning between the groups to 368 women who were 60-70 years old at completion of the questionnaire (premenopausal group, n=226, postmenopausal group, n=142). In 496 women with a premenopausal risk-reducing salpingo-oophorectomy we compared sexual functioning between women in the early premenopausal group (n=151) and the later premenopausal group (n=345). Differences between groups were analyzed using multiple regression analyses adjusting for current age, breast cancer history, use of hormone replacement therapy, body mass index, chronic medication use (yes/no) and body image.Results: Mean time since risk-reducing salpingo-oophorectomy was 20.6 years in the premenopausal group and 10.6 years in the postmenopausal group (p-value <.001). In the premenopausal group, mean age at questionnaire completion was 62.7 years, versus 67.0 years in the postmenopausal group (p<.001). In the premenopausal group, 47.4% was still sexually active, compared to 48.9% of the postmenopausal group (p-value: .80). Current sexual pleasure scores were the same for women in the premenopausal group and the postmenopausal group (mean pleasure score 8.6, p-value .99). However, women in the premenopausal group more often reported substantial discomfort than women in the postmenopausal group (35.6% compared with 20.9%, p-value .04). After adjusting for confounders, premenopausal risk-reducing salpingo-oophorectomy was associated with substantially more discomfort during sexual intercourse, compared to postmenopausal risk-reducing salpingo-oophorectomy (odds ratio 3.1, 95% confidence interval 1.04; 9.4). Moreover, following premenopausal risk-reducing salpingo-oophorectomy, more severe complaints of vaginal dryness were observed (odds ratio 2.6, 95% confidence interval 1.4; 4.7). Women with a risk-reducing salpingo-oophorectomy before age 41 reported similar pleasure and discomfort scores as women with a risk-reducing salpingo-oophorectomy between ages 41 and 45.Conclusion: More than 15 years after premenopausal risk-reducing salpingo-oophorectomy, the proportion of sexually active women was comparable to that among women with a postmenopausal risk-reducing salpingo-oophorectomy. However, after a premenopausal risk-reducing salpingo-oophorectomy, women experienced more vaginal dryness and more often had substantial sexual discomfort during sexual intercourse. This did not lead to less pleasure with sexual activity. [ABSTRACT FROM AUTHOR]

We present the case history of 2 patients with low-density lipoprotein receptor–negative compound heterozygous familial hypercholesterolemia who did not receive lipoprotein apheresis. We describe the subsequent effect of all lipid-lowering medications during their life course including resins, statins, ezetimibe, nicotinic acid/laropiprant, mipomersen, and lomitapide. These cases tell the story of siblings affected with this rare disease, who are free of symptoms but still are at a very high cardiovascular disease risk, and their treatment from childhood. [ABSTRACT FROM AUTHOR]

Introduction Autosomal dominant hypercholesterolemia (ADH), characterized by high-plasma low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease (CVD) risk, is caused by mutations in LDLR , APOB , and/or PCSK9 . Objective To describe the clinical characteristics of “double-heterozygous carriers,” with 2 mutations in 2 different ADH causing genes, that is, LDLR and APOB or LDLR and PCSK9 . Methods Double heterozygotes were identified in the database of the national referral laboratory for DNA diagnostics of inherited dyslipidemias. We collected the medical data (comprising lipids and CVD events) from double heterozygotes and compared these with data from their heterozygous and unaffected relatives and homozygote/compound heterozygous LDLR mutation carriers, identified in a previously described cohort (n = 45). Results A total of 28 double heterozygotes (23 LDLR/APOB and 5 LDLR/PCSK9 mutation carriers) were identified. Off treatment, LDL-C levels were significantly higher in double heterozygotes (mean ± SD, 8.4 ± 2.8 mmol/L) compared with 28 heterozygous (5.6 ± 2.2) and 18 unaffected relatives (2.5 ± 1.1; P ≤ .01 for all comparisons) and significantly lower compared with homozygous/compound heterozygous LDLR mutation carriers (13.0 ± 5.1; P < .001). Conclusions Double-heterozygous carriers of mutations in ADH genes express an intermediate phenotype compared with heterozygous and homozygous/compound heterozygous carriers and might well be misconceived to suffer from a severe form of heterozygous ADH. The molecular identification of double heterozygosity is of relevance from both a screening and an educational perspective. [ABSTRACT FROM AUTHOR]

Individuals with elevated LDL-cholesterol levels have an increased risk for cardiovascular disease. Despite lipid lowering strategies, however, a significant cardiovascular risk remains. Bekkering et al. show that monocytes from patients with familial hypercholesterolemia have a trained immunity phenotype and that lipid lowering with statins does not revert this pro-inflammatory phenotype. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated. Methods: We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies. Results: Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5–12.2] versus odds ratio, 1.2 [95% CI, 0.6–2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8–8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia. Conclusions: Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531. [ABSTRACT FROM AUTHOR]

Background: An atherogenic lipid profile is a risk factor for the initiation and progression of atherosclerosis. This ultimately leads to cardiovascular disease. Women with a history of hypertensive disorders of pregnancy are at increased risk of sustained hypertension and cardiovascular disease later in life. Currently it is unclear whether dyslipidemia during pregnancy contributes to these risks.Objective: The objective of the study was to determine the associations between early pregnancy maternal lipid profile, hypertensive disorders of pregnancy, and blood pressure during and years after pregnancy.Study Design: We included 5690 women from the Generation R Study, an ongoing population-based prospective birth cohort. Two hundred eighteen women (3.8%) developed gestational hypertension and 139 (2.4%) preeclampsia. A maternal lipid profile consisting of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, remnant cholesterol, and non-high-density lipoprotein cholesterol was determined in early pregnancy (median, 13.4 weeks of gestation). Systolic and diastolic blood pressures were measured in early, mid-, and late pregnancy and 6 and 9 years after pregnancy.Results: Triglycerides and remnant cholesterol in early pregnancy were positively associated with preeclampsia. Maternal lipid levels in early pregnancy were not associated with gestational hypertension. Total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and especially triglycerides and remnant cholesterol were positively associated with blood pressure in pregnancy and 6 and 9 years after pregnancy. Triglycerides and remnant cholesterol are positively associated with sustained hypertension 6 and 9 years after pregnancy.Conclusion: An atherogenic lipid profile in early pregnancy reflecting impaired triglyceride-rich lipoprotein metabolism is independently associated with preeclampsia and blood pressure throughout pregnancy but also with sustained hypertension long term postpartum. Lipid levels in early pregnancy may help to identify women at risk for future hypertension and perhaps also women at risk for future cardiovascular disease. [ABSTRACT FROM AUTHOR]

Introduction Metabolic syndrome, characterized by abdominal obesity, insulin resistance, hypertension and hyperlipidemia has become a major health problem of the modern world. Metabolic syndrome is associated with adverse perinatal outcomes, such as a neonate born large for gestational age (LGA). Little is known about the role of maternal lipid concentrations in this association. Possibly, an atherogenic lipid profile in early pregnancy is a risk factor for adverse perinatal outcomes. Objective To determine the association of maternal glucose and lipid concentrations in early pregnancy with perinatal outcomes: LGA, small for gestational age (SGA), and spontaneous preterm birth (sPTB). Methods We included 5692 women from The Generation R Study; a prospective population-based birth cohort. Maternal glucose and lipid concentrations including triglycerides, total-cholesterol, high-density lipoprotein-cholesterol (HDL-c) were measured in early pregnancy (median 13.4 weeks). Low-density lipoprotein-cholesterol (LDL-c), remnant-cholesterol and non-HDL-c were calculated. A birth weight above the 90th percentile was defined as LGA and below the 10th percentile as SGA. Spontaneous birth before 37 weeks of gestation was defined as sPTB. Results Triglycerides and remnant-cholesterol were positively associated with the risk for LGA. These associations were partly mediated by maternal glucose concentrations in early pregnancy (10.9% and 9.0% respectively). HDL-c was negatively associated with the risk for LGA. Women with an atherogenic lipid profile (high triglycerides with either high total-cholesterol, high remnant-cholesterol or low HDL-c) were most at risk for a LGA child. We observed no associations between lipid concentrations in early pregnancy and the risk for SGA or sPTB. Discussion An atherogenic lipid profile in early pregnancy is associated with a higher risk for a LGA child. This association is partly mediated by maternal glucose concentration in early pregnancy. Assessing maternal lipid profile in early pregnancy might help to identify high-risk pregnancies in an early stage. [ABSTRACT FROM AUTHOR]

Introduction An atherogenic lipid profile is a risk factor for atherosclerosis and consequently for stroke and cardiovascular disease (CVD). An atherogenic lipid profile can cause endothelial dysfunction and consequently higher blood pressure (BP). Placentas of women with a gestational hypertensive disorder (GHD) are histologically comparable to an early stage of atherosclerosis. Objective To determine the association between maternal lipid profile in early pregnancy, GHD and BP throughout pregnancy and six and nine years after pregnancy. Methods We included 5692 women from The Generation R Study; an ongoing population-based prospective birth cohort. 218 (4.1%) women developed gestational hypertension (GH) and 139 (2.6%) women developed pre-eclampsia (PE). Maternal lipid levels included total-cholesterol, triglycerides and HDL-c, and were measured in early pregnancy (median 13.4 weeks of gestation). LDL-c, remnant cholesterol and non-HDL-c were calculated. Systolic and diastolic BP were measured in early, mid- and late pregnancy, and six and nine years after pregnancy. Results In the total population, total-cholesterol, triglycerides, LDL-c, remnant cholesterol and non-HDL-c were positively associated with BP in early, mid- and late pregnancy, six and nine years after pregnancy. Women with PE had higher levels of triglycerides and remnant cholesterol in early pregnancy compared to those with a normotensive pregnancy. Maternal lipid levels in early pregnancy were not associated with GH. Discussion An atherogenic lipid profile in pregnancy is positively associated with BP throughout pregnancy, and six and nine years after pregnancy. In particular triglycerides are important for the risk for PE. Lipid levels in early pregnancy might help to identify women at risk for not only PE, but also future hypertension and consequently initiate early prevention of future CVD. [ABSTRACT FROM AUTHOR]

Background A large proportion of patients with heterozygous familial hypercholesterolemia (heFH) do not reach low-density lipoprotein cholesterol (LDL-c) levels advocated by international guidelines (<70 mg/dL or <100 mg/dL). Objective We set out to model which proportion of patients reach targets using conventional and novel therapies. Methods We performed a cross-sectional analysis in a large cohort of genetically identified heFH patients and calculated the proportion reaching treatment targets in four scenarios: (1) after 50% LDL-c reduction (representing maximal dose statin); (2) after 70% LDL-c reduction (maximal dose statin + ezetimibe); (3) additional 40% LDL-c reduction representing cholesteryl ester transfer protein inhibitor (CETPi); and (4) 60% LDL-c reduction (proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9i]), on top of scenario 2. We applied 100% adherence rates and literature-based adherence rates from 62% to 80%. Results We included 1,059 heFH patients with and 9,420 heFH patients without coronary heart disease (CHD). With maximal dose statin, 8.3% and 48.1% of patients with and without CHD would reach their recommended LDL-c targets, respectively. This increases to 54.3% and 93.2% when ezetimibe is added. Addition of CETPi increases these numbers to 95.7% and 99.7%, whereas adding PCSK9i would result in 99.8% and 100% goal attainment. Using literature-based adherence rates, these numbers decrease to 3.8% and 27.3% for maximal dose statin, 5.8% and 38.9% combined with ezetimibe, 31.4% and 81.2% when adding CETPi, and 40.3% and 87.1% for addition of PCSK9i. Conclusions Less than 10% with and 50% of heFH patients without CHD would reach treatment targets with maximal dose statin, but this substantially increases on addition of ezetimibe, CETPi, or PCSK9i. However, considering recently published adherence data, this might be lower in real life, especially in heFH patients with CHD. [ABSTRACT FROM AUTHOR]

Background Gestational hypertensive disorders (GHDs), including gestational hypertension and preeclampsia, are associated with an increased risk of cardiovascular disease in later life, possibly through an atherogenic lipid profile. Objective The objective of this study is to assess if women with a previous GHD have a more atherogenic lipid profile 6 years after pregnancy compared to women with a previous normotensive pregnancy. Methods In a population-based prospective cohort study, we included 4933 women during pregnancy, including 302 women with a GHD. Six years after pregnancy, we determined maternal lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein[a], and apolipoprotein B) and glucose levels. Results Women with a previous GHD had a more atherogenic lipid profile 6 years after pregnancy compared to women with a previous normotensive pregnancy. These atherogenic lipid profiles were a result of higher levels of triglycerides, low-density lipoprotein cholesterol, and apolipoprotein B and lower levels of high-density lipoprotein cholesterol. Differences in lipid profile between women with a previous GHD and women with a previous normotensive pregnancy were attenuated after adjustment for prepregnancy body mass index. Between women from both groups, no differences were observed in total cholesterol, lipoprotein[a], and glucose levels. Conclusion Women with a previous GHD show a more atherogenic lipid profile 6 years after pregnancy than women with a previous normotensive pregnancy. The increased risk of cardiovascular disease after a GHD might result from an atherogenic lipid profile after pregnancy, primarily driven by prepregnancy body mass index. [ABSTRACT FROM AUTHOR]

Introduction: Women with a history of preeclampsia have an increased risk of developing cardiovascular disease (CVD) later in life. Classical risk scores are not suitable as risk estimates of CVD in this young population. Recent recommendations from the American Heart Association are aimed to improve cardiovascular health (CVH). Objectives: Examining CVH by Health Life Check (HLC) (http://mylifecheck.heart.org/) in previously severe preeclamptic women is part of our cardiovascular risk follow-up program. Final score is a scale from 1 to 10, where 10 represents ideal CVH. Results: Since 2011 HLC is offered to all women in this program. So far, 213 women were included, 148 (70%) underwent a CVH assessment by performing HLC between three months and one year after delivery. The overall HLC score was 7.4 (median; range: 0.8–10.0) at 3.6 months after the delivery. Only 2 out of 148 women (1.4%) had an ideal score. HLC score was 7.1 (median; range: 0.8–10.0) for 48 women who had a HLC score within 6 months after delivery versus 8.2 (median; range: 2.6–9.8) in the second half of the first year after delivery. Conclusion: These are the first data on CVH in women after severe preeclampsia. Only 1.4% of these women had an ideal score. Active counselling of these women could be the reason of the improved score over time. We showed that CVH as assessed by HLC is an excellent tool for cardiovascular risk management in this specific group of women. [Copyright &y& Elsevier]

Introduction Women with preeclampsia or pregnancy induced hypertension (PIH) show metabolic aberrations during pregnancy similar to the metabolic syndrome. These women also are at increased risk of cardiovascular disease later in life. Objective To assess whether women with preeclampsia or PIH have more unfavorable metabolic outcomes six years after pregnancy compared to normotensive women. Methods This study was embedded in the Generation R study, a population-based prospective cohort study. Information on pregnancy and metabolic outcomes six years after pregnancy was available in 4933 women. We measured total body and abdominal fat distribution, weight and plasma lipid concentrations (total cholesterol, LDL-c, HDL-c, triglycerides, Apolipoprotein-B (Apo-B), lipoprotein (a) (lp-a)). Results Compared with normotensive women, women with PIH had higher Apo-B (0.05g/l; 95%CI 0.02, 0.08), LDL-c (0.13 mmol/l; 95%CI 0.04, 0.22), triglyceride (0.11 mmol/l; 95%CI 0.01, 0.21) and total cholesterol concentrations (0.15 mmol/l; 95%CI 0.02, 0.29) and lower HDL-c concentrations (−0.06 mmol/l; 95%CI −0.11, −0.01). No differences were observed in lipid concentrations between normotensive and preeclamptic women. Women with PIH or preeclampsia both had higher body fat percentages (0.03%; 95%CI 0.02, 0.04 and 0.02%; 0.00, 0.04), higher BMI (3.6 kg/m 2 ; 95%CI 2.9, 4.2 and 2.4 kg/m 2 ; 1.4, 3.4, respectively) and increased risk of clustering of metabolic risk factors (OR 2.2; 95%CI 1.4, 3.3 and OR 2.3; 95%CI 1.3, 4.3, respectively) compared with normotensive women. These associations attenuated after adjustment for maternal weight gain after pregnancy. Early pregnancy weight seems to be a predictor for these unfavorable outcomes (figure). Conclusion Hypertensive pregnancy disorders, especially PIH, were associated with adverse metabolic outcomes and an increased risk of clustering of metabolic risk factors six years after pregnancy compared to normotensive women. We therefore advise to perform regular metabolic check-up on these women after delivery. [ABSTRACT FROM AUTHOR]

Introduction: Women with a history of preeclampsia have an increased risk of developing cardiovascular disease (CVD) later in life. 24-hour ambulatory blood pressure measurement is considered to be the gold-standard for diagnosing hypertension. Data on 24-hour ambulatory blood pressure measurement in women with a history of preeclampsia are scarce. Objectives: To evaluate hypertension in previously severe preeclamptic women, 24-hour ambulatory blood pressure measurements were performed one year after delivery as part of our cardiovascular risk follow-up program. Results: Since 2011 213 women were included in this program. 24-hour ambulatory blood pressure measurement was performed in 90 out of 121 women (74%) who completed follow-up one year after delivery. Systolic blood pressure was 121 mm Hg (median; range 96-157) and diastolic blood pressure 78mm Hg (median; range 62–114). Twenty-three women (26.0%) used antihypertensive medication one year postpartum. Blood pressure levels were not significantly different between women with and without medication. Five women (5/67, 7.5%) of those not using antihypertensives, were diagnosed as having hypertension by this measurement. Conclusion: These data show that 30% of these previously severe preeclamptic women have persisting hypertension one year postpartum. These data stress the importance of close monitoring of blood pressure in these women. [Copyright &y& Elsevier]